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Sample records for metabolic profiling method

  1. [Analysis of the effect of enzymes on microbial community metabolic profiles during composting using biolog method].

    PubMed

    Feng, Chong-ling; Zeng, Guang-ming; Huang, Dan-lian; Hu, Shuang; Su, Feng-feng; Zhao, Mei-hua; Lai, Cui

    2009-10-15

    The effects of enzymes on organic material degradation and microbial communities metabolic profiles during composting process were studied using Biolog method, and together with cluster analysis and PCA. The results showed that, adding the enzyme solution in the composting could increase the degradation rate of organic material by 4.90%. The microbial community metabolic results of cluster analysis showed that when the enzyme solution was added into the compost, the carbon metabolic capability of intermediate metabolite was improved. The results of PCA indicated that when the enzyme solution was added, microbial communities enhanced the metabolic capability of miscellaneous, polymers, amino acids and amides carbon substrates, which results in the efficient degradation of organic substance. In addition, cluster analysis of each composting phase showed that the effects of the enzymes solution on microbial community metabolism were mainly observed on 6 d and 30 d, which promoted the composting process.

  2. Profiling metabolic networks to study cancer metabolism.

    PubMed

    Hiller, Karsten; Metallo, Christian M

    2013-02-01

    Cancer is a disease of unregulated cell growth and survival, and tumors reprogram biochemical pathways to aid these processes. New capabilities in the computational and bioanalytical characterization of metabolism have now emerged, facilitating the identification of unique metabolic dependencies that arise in specific cancers. By understanding the metabolic phenotype of cancers as a function of their oncogenic profiles, metabolic engineering may be applied to design synthetically lethal therapies for some tumors. This process begins with accurate measurement of metabolic fluxes. Here we review advanced methods of quantifying pathway activity and highlight specific examples where these approaches have uncovered potential opportunities for therapeutic intervention.

  3. The development and validation of a fast and robust dried blood spot based lipid profiling method to study infant metabolism.

    PubMed

    Koulman, Albert; Prentice, Philippa; Wong, Max C Y; Matthews, Lee; Bond, Nicholas J; Eiden, Michael; Griffin, Julian L; Dunger, David B

    2014-01-01

    Early life exposures and metabolic programming are associated with later disease risk. In particular lipid metabolism is thought to play a key role in the development of the metabolic syndrome and insulin resistance in later life. Investigative studies of metabolic programming are limited by the ethics and practicalities of sample collection in small infants. Dried blood spots on filter paper, derived from heel pricks are considered as the most suitable option for this age group. We validated a novel lipid profiling method, based on high resolution mass spectrometry to successfully determine the lipid composition of infants using dried blood spots. The spotting and air drying of blood on paper has noticeable effects on many of the lipids, leading to lipid oxidation and hydrolysis, which demand careful interpretation of the obtained data. We compared the lipid profiles from plasma or whole blood samples and the results from dried blood spots to determine if these revealed the same inter-subject differences. The results from dried blood spots were no less reproducible than other lipid profiling methods which required comparatively larger sample volumes. Therefore, lipid profiles obtained from dried blood spots can be successfully used to monitor infancy lipid metabolism and we show significant differences in the lipid metabolism of infants at age 3 versus 12 months.

  4. HPLC method for amino acids profile in biological fluids and inborn metabolic disorders of aminoacidopathies.

    PubMed

    Babu, S V Suresh; Shareef, M M; Shetty, A Pavan Kumar; Shetty, K Taranath

    2002-07-01

    Quantification of total and individual amino acids in biological fluids such as plasma, urine and cerebrospinal fluid has an important diagnostic implication in laboratory medicine. The present paper describes protocols for the assay of total amino acids by modified method based on dinitrophenyl and HPLC profile involving pre-column derivatization with o-pthalaldehyde (OPA) derivatization, respectively. The method, based on the alkylation of-SH groups prior to OPA derivatization of amino acids followed by reverse phase high performance liquid chromatography, provide a comprehensive profile of more than twenty amino acids (including-SH group containing) in a single run lasting about 45 minutes. The present study, apart from establishing the normal profile of amino acids in plasma of Indian sub population, also presents HPLC profile for some of the rare amino acidopathies.

  5. Metabolic profiling of praziquantel enantiomers.

    PubMed

    Wang, Haina; Fang, Zhong-Ze; Zheng, Yang; Zhou, Kun; Hu, Changyan; Krausz, Kristopher W; Sun, Dequn; Idle, Jeffrey R; Gonzalez, Frank J

    2014-07-15

    Praziquantel (PZQ), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. In the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based metabolomics was employed to decipher the metabolic pathways and enantioselective metabolic differences of PZQ. Many phase I and four new phase II metabolites were found in urine and feces samples of mice 24h after dosing, indicating that the major metabolic reactions encompassed oxidation, dehydrogenation, and glucuronidation. Differences in the formation of all these metabolites were observed between (R)-PZQ and (S)-PZQ. In an in vitro phase I incubation system, the major involvement of CYP3A, CYP2C9, and CYP2C19 in the metabolism of PZQ, and CYP3A, CYP2C9, and CYP2C19 exhibited different catalytic activity toward the PZQ enantiomers. Apparent Km and Vmax differences were observed in the catalytic formation of three mono-oxidized metabolites by CYP2C9 and CYP3A4 further supporting the metabolic differences for PZQ enantiomers. Molecular docking showed that chirality resulted in differences in substrate location and conformation, which likely accounts for the metabolic differences. In conclusion, in silico, in vitro, and in vivo methods revealed the enantioselective metabolic profile of praziquantel.

  6. Metabolic profiling of Klebsiella oxytoca: evaluation of methods for extraction of intracellular metabolites using UPLC/Q-TOF-MS.

    PubMed

    Park, Changhun; Yun, Seokhun; Lee, Sang Yup; Park, Kyungmoon; Lee, Jinwon

    2012-06-01

    The global pool of intracellular metabolites is a reflection of all the metabolic functions of an organism. In the absence of in situ methods capable of directly measuring metabolite pools, intracellular metabolite measurements need to be performed after an extraction procedure. In this study, we evaluated the optimization of technologies for generation of a global metabolomics profile for intracellular metabolites in Klebsiella oxytoca. Intracellular metabolites of K. oxytoca were extracted at the early stationary phase using six different common extraction procedures, including cold methanol, boiling ethanol, methanol/chloroform combinations, hot water, potassium hydroxide, and perchloric acid. The metabolites were subsequently collected for further analysis, and intracellular metabolite concentration profiles were generated using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. During analysis, the stability of metabolites extracted using cold methanol was clearly higher than that obtained by other extraction methods. For the majority of metabolites, extracts generated in this manner exhibited the greatest recovery, with high reproducibility. Therefore, the use of cold ethanol was the best extraction method for attaining a metabolic profile. However, in another parallel extraction method, perchloric acid may also be required to maximize the range of metabolites recovered, particularly to extract glucose 1-phosphate and NADPH.

  7. Gas chromatography-mass spectrometric method for metabolic profiling of tobacco leaves.

    PubMed

    Li, Yong; Pang, Tao; Li, Yanli; Wang, Xiaolin; Li, Qinghua; Lu, Xin; Xu, Guowang

    2011-06-01

    A gas chromatography-mass spectrometric method was developed for profiling of tobacco leaves. The differentiation among tobacco leaves planted in two different regions was investigated. Prior to analysis, the extraction solvent formulation was optimized and a combination of water, methanol and acetonitrile with a volume ratio of 3:1:1 was found to be optimal. The reproducibility of the method was satisfactory. Kendall tau-b rank correlation coefficients were equal to 1 (p<0.05) for 82% of the resolved peaks (up to 95% of the overall peak areas), indicating the good response correlation. Forty-four compounds including 9 saccharides, 9 alcohols, 9 amino acids, 16 organic acids and phosphoric acid were identified based on standard compounds. The method was successfully applied for profiling of tobacco leaves from Zimbabwe and Yunnan of China. Our result revealed that levels of saccharides and their derivatives including xylose, ribose, fructose, glucose, turanose, xylitol and glyceric acid were more abundant while sucrose, glucitol and D-gluconic acid were less abundant in tobacco leaves from Yunnan as compared to those from Zimbabwe. Amino acids such as L-alanine, L-tyrosine and L-threonine were found to be richer in Zimbabwe tobacco than in Yunnan tobacco.

  8. Metabolic profiling reveals key metabolic features of renal cell carcinoma.

    PubMed

    Catchpole, Gareth; Platzer, Alexander; Weikert, Cornelia; Kempkensteffen, Carsten; Johannsen, Manfred; Krause, Hans; Jung, Klaus; Miller, Kurt; Willmitzer, Lothar; Selbig, Joachim; Weikert, Steffen

    2011-01-01

    Recent evidence suggests that metabolic changes play a pivotal role in the biology of cancer and in particular renal cell carcinoma (RCC). Here, a global metabolite profiling approach was applied to characterize the metabolite pool of RCC and normal renal tissue. Advanced decision tree models were applied to characterize the metabolic signature of RCC and to explore features of metastasized tumours. The findings were validated in a second independent dataset. Vitamin E derivates and metabolites of glucose, fatty acid, and inositol phosphate metabolism determined the metabolic profile of RCC. α-tocopherol, hippuric acid, myoinositol, fructose-1-phosphate and glucose-1-phosphate contributed most to the tumour/normal discrimination and all showed pronounced concentration changes in RCC. The identified metabolic profile was characterized by a low recognition error of only 5% for tumour versus normal samples. Data on metastasized tumours suggested a key role for metabolic pathways involving arachidonic acid, free fatty acids, proline, uracil and the tricarboxylic acid cycle. These results illustrate the potential of mass spectroscopy based metabolomics in conjunction with sophisticated data analysis methods to uncover the metabolic phenotype of cancer. Differentially regulated metabolites, such as vitamin E compounds, hippuric acid and myoinositol, provide leads for the characterization of novel pathways in RCC.

  9. Capillary electrophoresis with UV detection and mass spectrometry in method development for profiling metabolites of steroid hormone metabolism.

    PubMed

    Sirén, Heli; Seppänen-Laakso, Tuulikki; Oresic, Matej

    2008-08-15

    The aim of this study was to develop a method for comprehensive profiling of metabolites involved in mammalian steroid metabolism. The study was performed using the partial filling micellar electrokinetic chromatography (PF-MEKC) technique for determination of endogenous low-hydrophilic steroids. The detection techniques in capillary electrophoresis were UV absorption and electrospray mass spectrometry (ESI-MS). Thirteen steroids were included in the method development, and the selected were metabolites involved in major pathways of steroid biosynthesis. Although only eight of them could be separated and detected with UV, they could be identified by ESI-MS using selected ion monitoring (SIM) technique. Tandem MS spectra were also collected. UV detection was more sensitive than MS due to better separation of compounds and the selective signal sensitivity. The lowest limits of detection were 10-100 ng/mL for cortisone, corticosterone, hydrocortisone and testosterone. The other steroids could be detected at 500-1000 ng/mL. The identification of cortisone, corticosterone, hydrocortisone, estrogen and testosterone were made in patient urine samples and their concentrations were 1-40 microg/L.

  10. A rapid, simple method for the genetic discrimination of intact Arabidopsis thaliana mutant seeds using metabolic profiling by direct analysis in real-time mass spectrometry

    PubMed Central

    2011-01-01

    Background Efficient high throughput screening systems of useful mutants are prerequisite for study of plant functional genomics and lots of application fields. Advance in such screening tools, thanks to the development of analytic instruments. Direct analysis in real-time (DART)-mass spectrometry (MS) by ionization of complex materials at atmospheric pressure is a rapid, simple, high-resolution analytical technique. Here we describe a rapid, simple method for the genetic discrimination of intact Arabidopsis thaliana mutant seeds using metabolic profiling by DART-MS. Results To determine whether this DART-MS combined by multivariate analysis can perform genetic discrimination based on global metabolic profiling, intact Arabidopsis thaliana mutant seeds were subjected to DART-MS without any sample preparation. Partial least squares-discriminant analysis (PLS-DA) of DART-MS spectral data from intact seeds classified 14 different lines of seeds into two distinct groups: Columbia (Col-0) and Landsberg erecta (Ler) ecotype backgrounds. A hierarchical dendrogram based on partial least squares-discriminant analysis (PLS-DA) subdivided the Col-0 ecotype into two groups: mutant lines harboring defects in the phenylpropanoid biosynthetic pathway and mutants without these defects. These results indicated that metabolic profiling with DART-MS could discriminate intact Arabidopsis seeds at least ecotype level and metabolic pathway level within same ecotype. Conclusion The described DART-MS combined by multivariate analysis allows for rapid screening and metabolic characterization of lots of Arabidopsis mutant seeds without complex metabolic preparation steps. Moreover, potential novel metabolic markers can be detected and used to clarify the genetic relationship between Arabidopsis cultivars. Furthermore this technique can be applied to predict the novel gene function of metabolic mutants regardless of morphological phenotypes. PMID:21658279

  11. Sample-directed pseudotargeted method for the metabolic profiling analysis of rice seeds based on liquid chromatography with mass spectrometry.

    PubMed

    Zhang, Junjie; Zhao, Chunxia; Zeng, Zhongda; Luo, Ping; Zhao, Yanni; Zhao, Jieyu; Li, Lili; Lu, Xin; Xu, Guowang

    2016-01-01

    Rice is one of the most important food crops in the world. Metabolite composition in rice seeds varies significantly depending on genetic variety, climatic alternation and agricultural practice. Metabolomics is a powerful tool to reveal the metabolic response of rice to various conditions. In this work, a rice seed sample-directed pseudotargeted metabolomics method was first established and validated based on ultra high performance liquid chromatography with triple quadrupole mass spectrometry in the multiple reaction monitoring mode. A total of 749 and 617 ion pairs in positive and negative modes were achieved, respectively. Among them, about 200 metabolites were identified or tentatively identified. The developed method showed better linearity and repeatability than those of non-targeted metabolomics method. Good intra-day and inter-day precisions, recoveries and wide linear range were also obtained. Furthermore, the method was applied for the investigation of metabolic variation of rice seeds with two wild cultivars and their transgenic lines that were grown in two locations. Principal component analysis indicated that the effects of cultivar and location on metabolic variations were far more than those of gene modification. The nonparametric Mann-Whitney U test revealed that most metabolites were influenced by cultivar, location and gene modifications together.

  12. Metabolic Profiling of Alpine and Ecuadorian Lichens.

    PubMed

    Mittermeier, Verena K; Schmitt, Nicola; Volk, Lukas P M; Suárez, Juan Pablo; Beck, Andreas; Eisenreich, Wolfgang

    2015-10-01

    Non-targeted ¹H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The deviations in the overall metabolite fingerprints were low when analyzing S. alpinum collections from different locations or during different annual and seasonal periods. In contrast, metabolite profiles observed from extracts of different Alpine and Ecuadorian lichens clearly revealed genus- and species-specific profiles. The discriminating functions determining cluster formation in principle component analysis (PCA) were due to differences in the amounts of genus-specific compounds such as sticticin from the Sticta species, but also in the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose. However, varying concentrations of these metabolites from the same lichen species e.g., due to different environmental conditions appeared of minor relevance for the overall cluster formation in PCA. The metabolic clusters matched phylogenetic analyses using nuclear ribosomal DNA (nrDNA) internal transcribed spacer (ITS) sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be concluded that NMR-based non-targeted metabolic profiling is a useful tool in the chemo-taxonomy of lichens. The same approach could also facilitate the discovery of novel lichen metabolites on a rapid and systematical basis.

  13. Chemical fingerprint and metabolic profile analysis of Citrus reticulate 'Chachi' decoction by HPLC-PDA-IT-MS(n) and HPLC-Quadrupole-Orbitrap-MS method.

    PubMed

    Ye, Xiaolan; Cao, Di; Zhao, Xin; Song, Fenyun; Huang, Qinghua; Fan, Guorong; Wu, Fuhai

    2014-11-01

    A method incorporating HPLC-PDA-IT-MS(n) with HPLC-Quadrupole-Orbitrap-MS was developed for the investigation of chemical fingerprint of Citrus reticulate 'Chachi' decoction (CRCD) and metabolic profile of SD rat plasma sample after oral administration of CRCD (1.5 g herb/kg). A total of 27 chemical constituents of CRCD were identified from their MW, UV spectra, MS(n) data and retention behavior by comparing the results with those of the reference standards or literature. And 43 compounds were detected in dosed SD rat plasma samples, including 9 prototypes which were identified as hesperetin, isosinensetin, sinensetin, tetramethyl-O-isoscutellarein, nobiletin, tetramethyl-O-scutellarein, HMF (3,5,6,7,8,3',4'-heptamethoxyflavone), tangeretin and 5-demethylnobiletin and 34 metabolites underwent metabolic process of demethylation, glucuronide conjugation, sulfate conjugation or mixed modes. This is the first research for the metabolic profile of CRCD in SD rats, which could lay a foundation for the further studies of CRC or its formulation.

  14. Sheathless capillary electrophoresis‐mass spectrometry for anionic metabolic profiling

    PubMed Central

    Gulersonmez, Mehmet Can; Lock, Stephen; Hankemeier, Thomas

    2015-01-01

    The performance of CE coupled on‐line to MS via a sheathless porous tip sprayer was evaluated for anionic metabolic profiling. A representative metabolite mixture and biological samples were used for the evaluation of various analytical parameters, such as peak efficiency (plate numbers), migration time and peak area repeatability, and LODs. The BGE, i.e. 10% acetic acid (pH 2.2), previously used for cationic metabolic profiling was now assessed for anionic metabolic profiling by using MS detection in negative ion mode. For test compounds, RSDs for migration times and peak areas were below 2 and 11%, respectively, and plate numbers ranged from 60 000 to 40 0000 demonstrating a high separation efficiency. Critical metabolites with low or no retention on reversed‐phase LC could be efficiently separated and selectively analyzed by the sheathless CE‐MS method. An injection volume of only circa 20 nL resulted in LODs between 10 and 200 nM (corresponding to an amount of 0.4–4 fmol), which was an at least tenfold improvement as compared to LODs obtained by conventional CE‐MS approaches for these analytes. The methodology was applied to anionic metabolic profiling of glioblastoma cell line extracts. Overall, a sheathless CE‐MS method has been developed for highly efficient and sensitive anionic metabolic profiling studies, which can also be used for cationic metabolic profiling studies by only switching the MS detection and separation voltage polarity. PMID:26593113

  15. A novel approach to transforming a non-targeted metabolic profiling method to a pseudo-targeted method using the retention time locking gas chromatography/mass spectrometry-selected ions monitoring.

    PubMed

    Li, Yong; Ruan, Qiang; Li, Yanli; Ye, Guozhu; Lu, Xin; Lin, Xiaohui; Xu, Guowang

    2012-09-14

    Non-targeted metabolic profiling is the most widely used method for metabolomics. In this paper, a novel approach was established to transform a non-targeted metabolic profiling method to a pseudo-targeted method using the retention time locking gas chromatography/mass spectrometry-selected ion monitoring (RTL-GC/MS-SIM). To achieve this transformation, an algorithm based on the automated mass spectral deconvolution and identification system (AMDIS), GC/MS raw data and a bi-Gaussian chromatographic peak model was developed. The established GC/MS-SIM method was compared with GC/MS-full scan (the total ion current and extracted ion current, TIC and EIC) methods, it was found that for a typical tobacco leaf extract, 93% components had their relative standard deviations (RSDs) of relative peak areas less than 20% by the SIM method, while 88% by the EIC method and 81% by the TIC method. 47.3% components had their linear correlation coefficient higher than 0.99, compared with 5.0% by the EIC and 6.2% by TIC methods. Multivariate analysis showed the pooled quality control samples clustered more tightly using the developed method than using GC/MS-full scan methods, indicating a better data quality. With the analysis of the variance of the tobacco samples from three different planting regions, 167 differential components (p<0.05) were screened out using the RTL-GC/MS-SIM method, but 151 and 131 by the EIC and TIC methods, respectively. The results show that the developed method not only has a higher sensitivity, better linearity and data quality, but also does not need complicated peak alignment among different samples. It is especially suitable for the screening of differential components in the metabolic profiling investigation.

  16. Sample preparation optimization in fecal metabolic profiling.

    PubMed

    Deda, Olga; Chatziioannou, Anastasia Chrysovalantou; Fasoula, Stella; Palachanis, Dimitris; Raikos, Νicolaos; Theodoridis, Georgios A; Gika, Helen G

    2017-03-15

    Metabolomic analysis of feces can provide useful insight on the metabolic status, the health/disease state of the human/animal and the symbiosis with the gut microbiome. As a result, recently there is increased interest on the application of holistic analysis of feces for biomarker discovery. For metabolomics applications, the sample preparation process used prior to the analysis of fecal samples is of high importance, as it greatly affects the obtained metabolic profile, especially since feces, as matrix are diversifying in their physicochemical characteristics and molecular content. However there is still little information in the literature and lack of a universal approach on sample treatment for fecal metabolic profiling. The scope of the present work was to study the conditions for sample preparation of rat feces with the ultimate goal of the acquisition of comprehensive metabolic profiles either untargeted by NMR spectroscopy and GC-MS or targeted by HILIC-MS/MS. A fecal sample pooled from male and female Wistar rats was extracted under various conditions by modifying the pH value, the nature of the organic solvent and the sample weight to solvent volume ratio. It was found that the 1/2 (wf/vs) ratio provided the highest number of metabolites under neutral and basic conditions in both untargeted profiling techniques. Concerning LC-MS profiles, neutral acetonitrile and propanol provided higher signals and wide metabolite coverage, though extraction efficiency is metabolite dependent. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Slow Magic Angle Sample Spinning: A Non- or Minimally Invasive Method for High- Resolution 1H Nuclear Magnetic Resonance (NMR) Metabolic Profiling

    SciTech Connect

    Hu, Jian Z.

    2011-05-01

    High resolution 1H magic angle spinning nuclear magnetic resonance (NMR), using a sample spinning rate of several kHz or more (i.e., high resolution-magic angle spinning (hr-MAS)), is a well established method for metabolic profiling in intact tissues without the need for sample extraction. The only shortcoming with hr-MAS is that it is invasive and is thus unusable for non-destructive detections. Recently, a method called slow-MAS, using the concept of two dimensional NMR spectroscopy, has emerged as an alternative method for non- or minimal invasive metabolomics in intact tissues, including live animals, due to the slow or ultra-slow-sample spinning used. Although slow-MAS is a powerful method, its applications are hindered by experimental challenges. Correctly designing the experiment and choosing the appropriate slow-MAS method both require a fundamental understanding of the operation principles, in particular the details of line narrowing due to the presence of molecular diffusion. However, these fundamental principles have not yet been fully disclosed in previous publications. The goal of this chapter is to provide an in depth evaluation of the principles associated with slow-MAS techniques by emphasizing the challenges associated with a phantom sample consisting of glass beads and H2O, where an unusually large magnetic susceptibility field gradient is obtained.

  18. Slow magic angle sample spinning: a non- or minimally invasive method for high-resolution 1H nuclear magnetic resonance (NMR) metabolic profiling.

    PubMed

    Hu, Jian Zhi

    2011-01-01

    High-resolution (1)H magic angle spinning nuclear magnetic resonance (NMR), using a sample spinning rate of several kilohertz or more (i.e., high-resolution magic angle spinning (hr-MAS)), is a well-established method for metabolic profiling in intact tissues without the need for sample extraction. The only shortcoming with hr-MAS is that it is invasive and is thus unusable for non-destructive detections. Recently, a method called slow MAS, using the concept of two-dimensional NMR spectroscopy, has emerged as an alternative method for non- or minimally invasive metabolomics in intact tissues, including live animals, due to the slow or ultra-slow sample spinning used. Although slow MAS is a powerful method, its applications are hindered by experimental challenges. Correctly designing the experiment and choosing the appropriate slow MAS method both require a fundamental understanding of the operation principles, in particular the details of line narrowing due to the presence of molecular diffusion. However, these fundamental principles have not yet been fully disclosed in previous publications. The goal of this chapter is to provide an in-depth evaluation of the principles associated with slow MAS techniques by emphasizing the challenges associated with a phantom sample consisting of glass beads and H(2)O, where an unusually large magnetic susceptibility field gradient is obtained.

  19. The evolution of metabolic profiling in parasitology.

    PubMed

    Holmes, E

    2010-08-01

    The uses of metabolic profiling technologies such as mass spectrometry and nuclear magnetic resonance spectroscopy in parasitology have been multi-faceted. Traditional uses of spectroscopic platforms focused on determining the chemical composition of drugs or natural products used for treatment of parasitic infection. A natural progression of the use of these tools led to the generation of chemical profiles of the parasite in in vitro systems, monitoring the response of the parasite to chemotherapeutics, profiling metabolic consequences in the host organism and to deriving host-parasite interactions. With the dawn of the post-genomic era the paradigm in many research areas shifted towards Systems Biology and the integration of biomolecular interactions at the level of the gene, protein and metabolite. Although these technologies have yet to deliver their full potential, metabolic profiling has a key role to play in defining diagnostic or even prognostic metabolic signatures of parasitic infection and in deciphering the molecular mechanisms underpinning the development of parasite-induced pathologies. The strengths and weaknesses of the various spectroscopic technologies and analytical strategies are summarized here with respect to achieving these goals.

  20. An overview of fecal sample preparation for global metabolic profiling.

    PubMed

    Deda, Olga; Gika, Helen G; Wilson, Ian D; Theodoridis, Georgios A

    2015-09-10

    The global metabolic profiling of feces represents a challenge for both analytical chemistry and biochemistry standpoints. As a specimen, feces is complex, not homogenous and rich in macromolecules and particulate, non-digested, matter that can present problems for analytical systems. Further to this, the composition of feces is highly dependent on short-term dietary factors whilst also representing the primary specimen where co-metabolism of the host organism and the gut-microbiota is expressed. Thus the presence and the content of metabolites can be a result of host metabolism, gut microbiota metabolism or co-metabolism. Successful sample preparation and metabolite analysis require that the methodology applied for sample preparation is adequate to compensate for the highly variable nature of the sample in order to generate useful data and provide insight to ongoing biochemical processes, thereby generating hypotheses. The current practices for processing fecal samples for global metabolic profiling are described with emphasis on critical aspects in sample preparation: e.g., homogenization, filtration, centrifugation, solvent extraction and so forth and also conditions/parameter selection are discussed. The different methods applied for feces processing prior to metabolite analysis are summarized and illustrated using selected examples to highlight the effect of sample preparation on the metabolic profile obtained. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Sheathless capillary electrophoresis-mass spectrometry for anionic metabolic profiling.

    PubMed

    Gulersonmez, Mehmet Can; Lock, Stephen; Hankemeier, Thomas; Ramautar, Rawi

    2016-04-01

    The performance of CE coupled on-line to MS via a sheathless porous tip sprayer was evaluated for anionic metabolic profiling. A representative metabolite mixture and biological samples were used for the evaluation of various analytical parameters, such as peak efficiency (plate numbers), migration time and peak area repeatability, and LODs. The BGE, i.e. 10% acetic acid (pH 2.2), previously used for cationic metabolic profiling was now assessed for anionic metabolic profiling by using MS detection in negative ion mode. For test compounds, RSDs for migration times and peak areas were below 2 and 11%, respectively, and plate numbers ranged from 60 000 to 40 0000 demonstrating a high separation efficiency. Critical metabolites with low or no retention on reversed-phase LC could be efficiently separated and selectively analyzed by the sheathless CE-MS method. An injection volume of only circa 20 nL resulted in LODs between 10 and 200 nM (corresponding to an amount of 0.4-4 fmol), which was an at least tenfold improvement as compared to LODs obtained by conventional CE-MS approaches for these analytes. The methodology was applied to anionic metabolic profiling of glioblastoma cell line extracts. Overall, a sheathless CE-MS method has been developed for highly efficient and sensitive anionic metabolic profiling studies, which can also be used for cationic metabolic profiling studies by only switching the MS detection and separation voltage polarity. © 2015 The Authors ELECTROPHORESIS Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  2. Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes

    PubMed Central

    Wopereis, Suzan; Rubingh, Carina M.; van Erk, Marjan J.; Verheij, Elwin R.; van Vliet, Trinette; Cnubben, Nicole H. P.; Smilde, Age K.; van der Greef, Jan; van Ommen, Ben; Hendriks, Henk F. J.

    2009-01-01

    Background The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. Methodology To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. Conclusions Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men. PMID:19242536

  3. Effect of acupuncture on rats with acute gouty arthritis inflammation: a metabonomic method for profiling of both urine and plasma metabolic perturbation.

    PubMed

    Wen, Si-Lan; Liu, Yu-Jie; Yin, Hai-Lin; Zhang, Liu; Xiao, Jin; Zhu, Hong-Yuan; Xue, Jin-Tao; Ye, Li-Ming

    2011-01-01

    Acute gouty arthritis is a common inflammation model with multiple pathogenic mechanisms seen in clinical practice, for which acupuncture may potentially be an alternative therapy. To investigate the effect of acupuncture on acute gouty arthritis and search for its mechanism, a metabonomic method was developed in this investigation. Acute gouty arthritis model rats were induced by monosodium urate (MSU) crystals. The urine and plasma samples were collected at several time points and the endogenous metabolites were analyzed by an ultra-performance liquid chromatography coupled with a mass spectrometry (UPLC-MS). Data were analyzed using principal components analysis (PCA) and partial least squares (PLS) analysis to compare metabolic profiles of MSU crystal-induced acute gouty arthritis rats with MSU crystal-induced acute gouty arthritis, treated with acupuncture rats. The results showed that acupuncture could restore the metabolite network that disturbed by MSU administration. Our study indicates that UPLC-MS-based metabonomics can be used as a potential tool for the investigation of biological effect of acupuncture on acute gouty arthritis.

  4. The metabolic network of Clostridium acetobutylicum: Comparison of the approximate Bayesian computation via sequential Monte Carlo (ABC-SMC) and profile likelihood estimation (PLE) methods for determinability analysis.

    PubMed

    Thorn, Graeme J; King, John R

    2016-01-01

    The Gram-positive bacterium Clostridium acetobutylicum is an anaerobic endospore-forming species which produces acetone, butanol and ethanol via the acetone-butanol (AB) fermentation process, leading to biofuels including butanol. In previous work we looked to estimate the parameters in an ordinary differential equation model of the glucose metabolism network using data from pH-controlled continuous culture experiments. Here we combine two approaches, namely the approximate Bayesian computation via an existing sequential Monte Carlo (ABC-SMC) method (to compute credible intervals for the parameters), and the profile likelihood estimation (PLE) (to improve the calculation of confidence intervals for the same parameters), the parameters in both cases being derived from experimental data from forward shift experiments. We also apply the ABC-SMC method to investigate which of the models introduced previously (one non-sporulation and four sporulation models) have the greatest strength of evidence. We find that the joint approximate posterior distribution of the parameters determines the same parameters as previously, including all of the basal and increased enzyme production rates and enzyme reaction activity parameters, as well as the Michaelis-Menten kinetic parameters for glucose ingestion, while other parameters are not as well-determined, particularly those connected with the internal metabolites acetyl-CoA, acetoacetyl-CoA and butyryl-CoA. We also find that the approximate posterior is strongly non-Gaussian, indicating that our previous assumption of elliptical contours of the distribution is not valid, which has the effect of reducing the numbers of pairs of parameters that are (linearly) correlated with each other. Calculations of confidence intervals using the PLE method back this up. Finally, we find that all five of our models are equally likely, given the data available at present. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Metabolic Risk Profile and Cancer in Korean Men and Women

    PubMed Central

    Kim, A-Rim; Kim, Eun-Jung; Seo, Hye-Young

    2016-01-01

    Objectives: Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. Methods: We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. Results: A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. Conclusions: The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women. PMID:27255073

  6. Metabolic connectivity: methods and applications.

    PubMed

    Yakushev, Igor; Drzezga, Alexander; Habeck, Christian

    2017-09-13

    Metabolic connectivity modelling aims to detect functionally interacting brain regions based on PET recordings with the glucose analogue [F]fluorodeoxyglucose (FDG). Here, we outline the most popular metabolic connectivity methods and summarize recent applications in clinical and basic neuroscience. Metabolic connectivity is modelled by various methods including a seed correlation, sparse inverse covariance estimation, independent component analysis and graph theory. Given its multivariate nature, metabolic connectivity possess added value relative to conventional univariate analyses of FDG-PET data. As such, metabolic connectivity provides valuable insights into pathophysiology and diagnosis of dementing, movement disorders, and epilepsy. Metabolic connectivity can also identify resting state networks resembling patterns of functional connectivity as derived from functional MRI data. Metabolic connectivity is a valuable concept in the fast-developing field of brain connectivity, at least as reasonable as functional connectivity of functional MRI. So far, the value of metabolic connectivity is best established in neurodegenerative disorders, but studies in other brain diseases as well as in the healthy state are emerging. Growing evidence indicates that metabolic connectivity may serve a marker of normal and pathological cognitive function. A relationship of metabolic connectivity with structural and functional connectivity is yet to be established.

  7. Indicators of dairy cow transition risks: Metabolic profiling revisited.

    PubMed

    Van Saun, R J

    2016-01-01

    Periparturient disease conditions affecting transition dairy cows have been recognized as a critical contributor to impaired dairy performance and have become a focal point of herd diagnostic investigations. Over the past 40 years use of blood sampling in the form of metabolic profiling has been applied to herd diagnostics with mixed impressions of diagnostic robustness. Research has greatly increased our understanding of underpinning mechanisms related to cow biology, management, environment and their interactions responsible for peripartum diseases. Elevated β-hydroxybutyrate (BHB) concentration (> 1.2 mmol/l) within 7-10 days following calving identifies high risk cows for therapeutic intervention. Herd evaluations with 15-25% of first week fresh cows with elevated BHB indicates significant disease risk and productive losses. Elevated peripartal serum nonesterified fatty acids (NEFA) also indicate increased disease risk. This review discusses documented (BHB, NEFA) and other potential analytes using individual or pooled samples useful for disease risk assessment or nutritional status and their application in risk-based or herd screening methods of herd metabolic profiling diagnostics. A pooled sample approach modified from the original Compton Metabolic Profile allows for more economic assessment of multiple analytes, though interpretation and herd-size application may be limited. Pooled samples between 5 and 10 individuals accurately represent arithmetic means of individuals. Most importantly metabolic profiles must be used in concert with other diagnostic metrics of animal and facility evaluations, body condition scoring and ration evaluation to be fully useful in herd evaluations.

  8. OVCAR-3 Spheroid-Derived Cells Display Distinct Metabolic Profiles

    PubMed Central

    Vermeersch, Kathleen A.; Wang, Lijuan; Mezencev, Roman; McDonald, John F.; Styczynski, Mark P.

    2015-01-01

    Introduction Recently, multicellular spheroids were isolated from a well-established epithelial ovarian cancer cell line, OVCAR-3, and were propagated in vitro. These spheroid-derived cells displayed numerous hallmarks of cancer stem cells, which are chemo- and radioresistant cells thought to be a significant cause of cancer recurrence and resultant mortality. Gene set enrichment analysis of expression data from the OVCAR-3 cells and the spheroid-derived putative cancer stem cells identified several metabolic pathways enriched in differentially expressed genes. Before this, there had been little previous knowledge or investigation of systems-scale metabolic differences between cancer cells and cancer stem cells, and no knowledge of such differences in ovarian cancer stem cells. Methods To determine if there were substantial metabolic changes corresponding with these transcriptional differences, we used two-dimensional gas chromatography coupled to mass spectrometry to measure the metabolite profiles of the two cell lines. Results These two cell lines exhibited significant metabolic differences in both intracellular and extracellular metabolite measurements. Principal components analysis, an unsupervised dimensional reduction technique, showed complete separation between the two cell types based on their metabolite profiles. Pathway analysis of intracellular metabolomics data revealed close overlap with metabolic pathways identified from gene expression data, with four out of six pathways found enriched in gene-level analysis also enriched in metabolite-level analysis. Some of those pathways contained multiple metabolites that were individually statistically significantly different between the two cell lines, with one of the most broadly and consistently different pathways, arginine and proline metabolism, suggesting an interesting hypothesis about cancerous and stem-like metabolic phenotypes in this pair of cell lines. Conclusions Overall, we demonstrate for the

  9. Noninvasive metabolic profiling for painless diagnosis of human diseases and disorders.

    PubMed

    Mal, Mainak

    2016-06-01

    Metabolic profiling provides a powerful diagnostic tool complementary to genomics and proteomics. The pain, discomfort and probable iatrogenic injury associated with invasive or minimally invasive diagnostic methods, render them unsuitable in terms of patient compliance and participation. Metabolic profiling of biomatrices like urine, breath, saliva, sweat and feces, which can be collected in a painless manner, could be used for noninvasive diagnosis. This review article covers the noninvasive metabolic profiling studies that have exhibited diagnostic potential for diseases and disorders. Their potential applications are evident in different forms of cancer, metabolic disorders, infectious diseases, neurodegenerative disorders, rheumatic diseases and pulmonary diseases. Large scale clinical validation of such diagnostic methods is necessary in future.

  10. Metabolic profiling of Alzheimer's disease brains

    NASA Astrophysics Data System (ADS)

    Inoue, Koichi; Tsutsui, Haruhito; Akatsu, Hiroyasu; Hashizume, Yoshio; Matsukawa, Noriyuki; Yamamoto, Takayuki; Toyo'Oka, Toshimasa

    2013-08-01

    Alzheimer's disease (AD) is an irreversible, progressive brain disease and can be definitively diagnosed after death through an examination of senile plaques and neurofibrillary tangles in several brain regions. It is to be expected that changes in the concentration and/or localization of low-molecular-weight molecules are linked to the pathological changes that occur in AD, and determining their identity would provide valuable information regarding AD processes. Here, we propose definitive brain metabolic profiling using ultra-performance liquid chromatography coupled with electrospray time-of-flight mass spectrometry analysis. The acquired data were subjected to principal components analysis to differentiate the frontal and parietal lobes of the AD/Control groups. Significant differences in the levels of spermine and spermidine were identified using S-plot, mass spectra, databases and standards. Based on the investigation of the polyamine metabolite pathway, these data establish that the downstream metabolites of ornithine are increased, potentially implicating ornithine decarboxylase activity in AD pathology.

  11. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling.

    PubMed

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R; Jijakli, Kenan; Salehi-Ashtiani, Kourosh

    2014-01-01

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates.

  12. Microalgal Metabolic Network Model Refinement through High-Throughput Functional Metabolic Profiling

    PubMed Central

    Chaiboonchoe, Amphun; Dohai, Bushra Saeed; Cai, Hong; Nelson, David R.; Jijakli, Kenan; Salehi-Ashtiani, Kourosh

    2014-01-01

    Metabolic modeling provides the means to define metabolic processes at a systems level; however, genome-scale metabolic models often remain incomplete in their description of metabolic networks and may include reactions that are experimentally unverified. This shortcoming is exacerbated in reconstructed models of newly isolated algal species, as there may be little to no biochemical evidence available for the metabolism of such isolates. The phenotype microarray (PM) technology (Biolog, Hayward, CA, USA) provides an efficient, high-throughput method to functionally define cellular metabolic activities in response to a large array of entry metabolites. The platform can experimentally verify many of the unverified reactions in a network model as well as identify missing or new reactions in the reconstructed metabolic model. The PM technology has been used for metabolic phenotyping of non-photosynthetic bacteria and fungi, but it has not been reported for the phenotyping of microalgae. Here, we introduce the use of PM assays in a systematic way to the study of microalgae, applying it specifically to the green microalgal model species Chlamydomonas reinhardtii. The results obtained in this study validate a number of existing annotated metabolic reactions and identify a number of novel and unexpected metabolites. The obtained information was used to expand and refine the existing COBRA-based C. reinhardtii metabolic network model iRC1080. Over 254 reactions were added to the network, and the effects of these additions on flux distribution within the network are described. The novel reactions include the support of metabolism by a number of d-amino acids, l-dipeptides, and l-tripeptides as nitrogen sources, as well as support of cellular respiration by cysteamine-S-phosphate as a phosphorus source. The protocol developed here can be used as a foundation to functionally profile other microalgae such as known microalgae mutants and novel isolates. PMID:25540776

  13. A fully validated GC-TOF-MS method for the quantification of fatty acids revealed alterations in the metabolic profile of fatty acids after smoking cessation.

    PubMed

    Goettel, Michael; Niessner, Reinhard; Pluym, Nikola; Scherer, Gerhard; Scherer, Max

    2017-01-15

    We developed and validated an efficient and robust method for the simultaneous quantification of 44 fatty acid species in human plasma via GC-TOF-MS. The method is characterized by its robustness, accuracy and precision covering a wide range of fatty acid species with various saturation degrees including short chain fatty acids (beginning with FA 4:0) and long chain fatty acids (up to FA 32:0). The fatty acids were methylated prior to analyses and subsequently detected as fatty acid methyl esters by means of GC-TOF-MS. A highly substituted polar column allowed the separation of geometrical and positional isomers of fatty acid species. The method was applied to plasma samples of a strictly diet controlled clinical smoking cessation study including 39 smokers followed over the course of three months after having quit. Statistical significant alterations within the fatty acid profile were observed when comparing the baseline (subjects still smoking) with one week, one month and three months of smoking cessation. After 3 months of smoking cessation, a partial recovery of alterations in the fatty acid profile evoked by smoking was observed. In conclusion, the developed fatty acid profiling method using GC-TOF-MS has proven as a reliable tool for the quantitative determination of 44 individual fatty acid species within clinical studies.

  14. Ensemble Kinetic Modeling of Metabolic Networks from Dynamic Metabolic Profiles

    PubMed Central

    Jia, Gengjie; Stephanopoulos, Gregory; Gunawan, Rudiyanto

    2012-01-01

    Kinetic modeling of metabolic pathways has important applications in metabolic engineering, but significant challenges still remain. The difficulties faced vary from finding best-fit parameters in a highly multidimensional search space to incomplete parameter identifiability. To meet some of these challenges, an ensemble modeling method is developed for characterizing a subset of kinetic parameters that give statistically equivalent goodness-of-fit to time series concentration data. The method is based on the incremental identification approach, where the parameter estimation is done in a step-wise manner. Numerical efficacy is achieved by reducing the dimensionality of parameter space and using efficient random parameter exploration algorithms. The shift toward using model ensembles, instead of the traditional “best-fit” models, is necessary to directly account for model uncertainty during the application of such models. The performance of the ensemble modeling approach has been demonstrated in the modeling of a generic branched pathway and the trehalose pathway in Saccharomyces cerevisiae using generalized mass action (GMA) kinetics. PMID:24957767

  15. Human serum metabolic profiles are age dependent

    PubMed Central

    Yu, Zhonghao; Zhai, Guangju; Singmann, Paula; He, Ying; Xu, Tao; Prehn, Cornelia; Römisch-Margl, Werner; Lattka, Eva; Gieger, Christian; Soranzo, Nicole; Heinrich, Joachim; Standl, Marie; Thiering, Elisabeth; Mittelstraß, Kirstin; Wichmann, Heinz-Erich; Peters, Annette; Suhre, Karsten; Li, Yixue; Adamski, Jerzy; Spector, Tim D; Illig, Thomas; Wang-Sattler, Rui

    2012-01-01

    Understanding the complexity of aging is of utmost importance. This can now be addressed by the novel and powerful approach of metabolomics. However, to date, only a few metabolic studies based on large samples are available. Here, we provide novel and specific information on age-related metabolite concentration changes in human homeostasis. We report results from two population-based studies: the KORA F4 study from Germany as a discovery cohort, with 1038 female and 1124 male participants (32–81 years), and the TwinsUK study as replication, with 724 female participants. Targeted metabolomics of fasting serum samples quantified 131 metabolites by FIA-MS/MS. Among these, 71/34 metabolites were significantly associated with age in women/men (BMI adjusted). We further identified a set of 13 independent metabolites in women (with P values ranging from 4.6 × 10−04 to 7.8 × 10−42, αcorr = 0.004). Eleven of these 13 metabolites were replicated in the TwinsUK study, including seven metabolite concentrations that increased with age (C0, C10:1, C12:1, C18:1, SM C16:1, SM C18:1, and PC aa C28:1), while histidine decreased. These results indicate that metabolic profiles are age dependent and might reflect different aging processes, such as incomplete mitochondrial fatty acid oxidation. The use of metabolomics will increase our understanding of aging networks and may lead to discoveries that help enhance healthy aging. PMID:22834969

  16. Metabolic rate meter and method

    NASA Technical Reports Server (NTRS)

    Taylor, T. I.; Ruderman, I. W. (Inventor)

    1968-01-01

    A method is described for measuring the dynamic metabolic rate of a human or animal. The ratio of the exhaled carbon dioxide to a known amount of C(13)02 introduced into the exhalation is determined by mass spectrometry. This provides an instantaneous measurement of the carbon dioxide generated.

  17. Genetic Networks of Liver Metabolism Revealed by Integration of Metabolic and Transcriptional Profiling

    PubMed Central

    Ferrara, Christine T.; Wang, Ping; Neto, Elias Chaibub; Stevens, Robert D.; Bain, James R.; Wenner, Brett R.; Ilkayeva, Olga R.; Keller, Mark P.; Blasiole, Daniel A.; Kendziorski, Christina; Yandell, Brian S.; Newgard, Christopher B.; Attie, Alan D.

    2008-01-01

    Although numerous quantitative trait loci (QTL) influencing disease-related phenotypes have been detected through gene mapping and positional cloning, identification of the individual gene(s) and molecular pathways leading to those phenotypes is often elusive. One way to improve understanding of genetic architecture is to classify phenotypes in greater depth by including transcriptional and metabolic profiling. In the current study, we have generated and analyzed mRNA expression and metabolic profiles in liver samples obtained in an F2 intercross between the diabetes-resistant C57BL/6 leptinob/ob and the diabetes-susceptible BTBR leptinob/ob mouse strains. This cross, which segregates for genotype and physiological traits, was previously used to identify several diabetes-related QTL. Our current investigation includes microarray analysis of over 40,000 probe sets, plus quantitative mass spectrometry-based measurements of sixty-seven intermediary metabolites in three different classes (amino acids, organic acids, and acyl-carnitines). We show that liver metabolites map to distinct genetic regions, thereby indicating that tissue metabolites are heritable. We also demonstrate that genomic analysis can be integrated with liver mRNA expression and metabolite profiling data to construct causal networks for control of specific metabolic processes in liver. As a proof of principle of the practical significance of this integrative approach, we illustrate the construction of a specific causal network that links gene expression and metabolic changes in the context of glutamate metabolism, and demonstrate its validity by showing that genes in the network respond to changes in glutamine and glutamate availability. Thus, the methods described here have the potential to reveal regulatory networks that contribute to chronic, complex, and highly prevalent diseases and conditions such as obesity and diabetes. PMID:18369453

  18. Metabolism profiling of amino-noscapine.

    PubMed

    Qu, Hua-Jun; Qian, Yang

    2016-04-01

    Amino-noscapine is a promising noscapine derivative undergoing R&D as an efficient anti-tumor drug. In vitro phase I metabolism incubation system was employed. In vitro samples were analyzed using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry. In vitro recombinant CYP isoforms screening was used to identify the drug-metabolizing enzymes involved in the metabolism of amino-noscapine. Multiple metabolics were formed, including the formation of metabolite undergoing cleavage of methylenedioxy group, hydroxylated metabolites, demethylated metabolites, and metabolites undergoing C-C cleavage. Nearly, all the CYP isoforms were involved in the metabolism of metabolites II, III, VII, IX, and X. CYP1A1 was demonstrated to be the major CYP isoform for the formation of metabolites IV and V. CYP1A1 and CYP3A4 mainly catalyzed the formation of metabolite VI. The metabolic formation of VIII was mainly catalyzed by CYP2C19 and CYP3A4. CYP3A4 was the main enzyme for the formation of XI. CYP2C9 mainly catalyzed the generation of metabolite XII. In conclusion, the metabolic pathway of amino-noscapine was elucidated in the present study using in vitro phase I incubation experiment, including the structural elucidation of metabolites and involved phase I drug-metabolizing enzymes. This information was helpful for the R&D of amino-noscapine.

  19. Metabolic Profiles Predict Adverse Events Following Coronary Artery Bypass Grafting

    PubMed Central

    Shah, Asad A.; Craig, Damian M.; Sebek, Jacqueline K.; Haynes, Carol; Stevens, Robert C.; Muehlbauer, Michael J.; Granger, Christopher B.; Hauser, Elizabeth R.; Newby, L. Kristin; Newgard, Christopher B.; Kraus, William E.; Hughes, G. Chad; Shah, Svati H.

    2012-01-01

    Objectives Clinical models incompletely predict outcomes following coronary artery bypass grafting. Novel molecular technologies may identify biomarkers to improve risk stratification. We examined whether metabolic profiles can predict adverse events in patients undergoing coronary artery bypass grafting. Methods The study population comprised 478 subjects from the CATHGEN biorepository of patients referred for cardiac catheterization who underwent coronary artery bypass grafting after enrollment. Targeted mass spectrometry-based profiling of 69 metabolites was performed in frozen, fasting plasma samples collected prior to surgery. Principal-components analysis and Cox proportional hazards regression modeling were used to assess the relation between metabolite factor levels and a composite outcome of post-coronary artery bypass grafting myocardial infarction, need for percutaneous coronary intervention, repeat coronary artery bypass grafting, or death. Results Over a mean follow-up of 4.3 ± 2.4 years, 126 subjects (26.4%) suffered an adverse event. Three principal-components analysis-derived factors were significantly associated with adverse outcome in univariable analysis: short-chain dicarboxylacylcarnitines (factor 2, P=0.001); ketone-related metabolites (factor 5, P=0.02); and short-chain acylcarnitines (factor 6, P=0.004). These three factors remained independently predictive of adverse outcome after multivariable adjustment: factor 2 (adjusted hazard ratio 1.23; 95% confidence interval [1.10-1.38]; P<0.001), factor 5 (1.17 [1.01-1.37], P=0.04), and factor 6 (1.14 [1.02-1.27], P=0.03). Conclusions Metabolic profiles are independently associated with adverse outcomes following coronary artery bypass grafting. These profiles may represent novel biomarkers of risk that augment existing tools for risk stratification of coronary artery bypass grafting patients and may elucidate novel biochemical pathways that mediate risk. PMID:22306227

  20. Metabolite Profiling Identifies Pathways Associated with Metabolic Risk in Humans

    PubMed Central

    Cheng, Susan; Rhee, Eugene P.; Larson, Martin G.; Lewis, Gregory D.; McCabe, Elizabeth L.; Shen, Dongxiao; Palma, Melinda J.; Roberts, Lee D.; Dejam, Andre; Souza, Amanda L.; Deik, Amy A.; Magnusson, Martin; Fox, Caroline S.; O'Donnell, Christopher J.; Vasan, Ramachandran S.; Melander, Olle; Clish, Clary B.; Gerszten, Robert E.; Wang, Thomas J.

    2012-01-01

    Background Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes and cardiovascular disease, the underlying biological mechanisms remain poorly understood. Methods and Results To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; N=1015) and the Malmö Diet and Cancer Study (MDC; N=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, dyslipidemia) were associated with multiple metabolites including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients −0.04 to −0.22, per 1-SD change in log-glutamine, P<0.001), glutamate (0.05 to 0.14, P<0.001), and glutamine-glutamate ratio (−0.05 to −0.20, P<0.001) in the discovery sample (FHS); similar associations were observed in the replication sample (MDC). High glutamine-glutamate ratio was associated with lower risk of incident diabetes in FHS (OR 0.79; adjusted P=0.03), but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance (P=0.01) and to lower blood pressure (P<0.05). Conclusions Biochemical profiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice. PMID:22496159

  1. Global Profiling Strategies for Mapping Dysregulated Metabolic Pathways in Cancer

    PubMed Central

    Benjamin, Daniel I.; Cravatt, Benjamin F.; Nomura, Daniel K.

    2012-01-01

    Cancer cells possess fundamentally altered metabolism that provides a foundation to support tumorigenicity and malignancy. Our understanding of the biochemical underpinnings of cancer has benefited from the integrated utilization of large-scale profiling platforms (e.g. genomics, proteomics, and metabolomics), which, together, can provide a global assessment of how enzymes and their parent metabolic networks become altered in cancer to fuel tumor growth. This review presents several examples of how these integrated platforms have yielded fundamental insights into dysregulated metabolism in cancer. We will also discuss questions and challenges that must be addressed to more completely describe, and eventually control, the diverse metabolic pathways that support tumorigenesis. PMID:23063552

  2. Large-scale profiling of metabolic dysregulation in ovarian cancer.

    PubMed

    Ke, Chaofu; Hou, Yan; Zhang, Haiyu; Fan, Lijun; Ge, Tingting; Guo, Bing; Zhang, Fan; Yang, Kai; Wang, Jingtao; Lou, Ge; Li, Kang

    2015-02-01

    Ovarian cancer is the leading cause of death in gynecologic malignancies. Profiling of endogenous metabolites has potential to identify changes caused by cancer and provide inspiring insights into cancer metabolism. To systematically investigate ovarian cancer metabolism, we performed metabolic profiling of 448 plasma samples related to epithelial ovarian cancer (EOC) based on ultra-performance liquid chromatography mass spectrometry in both positive and negative modes. These unbiased metabolomic profiles could well distinguish EOC from benign ovarian tumor (BOT) and uterine fibroid (UF). Fifty-three metabolites were identified as specific biomarkers for EOC, and this is the first report of piperine, 3-indolepropionic acid, 5-hydroxyindoleacetaldehyde and hydroxyphenyllactate as metabolic biomarkers of EOC. The AUC values of these metabolites for discriminating EOC from BOT/UF and early-stage EOC from BOT/UF were 0.9100/0.9428 and 0.8385/0.8624, respectively. Meanwhile, our metabolites were able to distinguish early-stage EOC from late-stage EOC with an AUC of 0.8801. Importantly, analysis of dysregulated metabolic pathways extends our current understanding of EOC metabolism. Metabolic pathways in EOC patients are mainly characterized by abnormal phospholipid metabolism, altered l-tryptophan catabolism, aggressive fatty acid β-oxidation and aberrant metabolism of piperidine derivatives. Together, these metabolic pathways provide a foundation to support cancer development and progression. In conclusion, our large-scale plasma metabolomics study yielded fundamental insights into dysregulated metabolism in ovarian cancer, which could facilitate clinical diagnosis, therapy, prognosis and shed new lights on ovarian cancer pathogenesis.

  3. Antihypertensive Drugs Metabolism: An Update to Pharmacokinetic Profiles and Computational Approaches

    PubMed Central

    Zisaki, Aikaterini; Miskovic, Ljubisa; Hatzimanikatis, Vassily

    2015-01-01

    Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmetics and nutritional supplements. Antihypertensive drugs are used for the treatment of high blood pressure, which is one the most frequent symptoms of the patients that undergo cardiovascular diseases such as myocardial infraction and strokes. In current cardiovascular disease pharmacology, four drug clusters - Angiotensin Converting Enzyme Inhibitors, Beta-Blockers, Calcium Channel Blockers and Diuretics - cover the major therapeutic characteristics of the most antihypertensive drugs. The pharmacokinetic and specifically the metabolic profile of the antihypertensive agents are intensively studied because of the broad inter-individual variability on plasma concentrations and the diversity on the efficacy response especially due to the P450 dependent metabolic status they present. Several computational methods have been developed with the aim to: (i) model and better understand the human drug metabolism; and (ii) enhance the experimental investigation of the metabolism of small xenobiotic molecules. The main predictive tools these methods employ are rule-based approaches, quantitative structure metabolism/activity relationships and docking approaches. This review paper provides detailed metabolic profiles of the major clusters of antihypertensive agents, including their metabolites and their metabolizing enzymes, and it also provides specific information concerning the computational approaches that have been used to predict the metabolic profile of several antihypertensive drugs. PMID:25341854

  4. Noninvasive metabolic profiling for painless diagnosis of human diseases and disorders

    PubMed Central

    Mal, Mainak

    2016-01-01

    Metabolic profiling provides a powerful diagnostic tool complementary to genomics and proteomics. The pain, discomfort and probable iatrogenic injury associated with invasive or minimally invasive diagnostic methods, render them unsuitable in terms of patient compliance and participation. Metabolic profiling of biomatrices like urine, breath, saliva, sweat and feces, which can be collected in a painless manner, could be used for noninvasive diagnosis. This review article covers the noninvasive metabolic profiling studies that have exhibited diagnostic potential for diseases and disorders. Their potential applications are evident in different forms of cancer, metabolic disorders, infectious diseases, neurodegenerative disorders, rheumatic diseases and pulmonary diseases. Large scale clinical validation of such diagnostic methods is necessary in future. PMID:28031956

  5. Metabolic profile in Chilota lambs grazing Calafatal.

    PubMed

    Gallardo, María Asunción; Noro, Mirela; De la Barra, Rodrigo; Pulido, Rubén

    2014-04-01

    The aim of this study was to determine the productive and metabolic response in Chilota lambs grazing Calafatal or naturalized pasture. The experiment was conducted at the Experimental Station Butalcura (INIA, Chiloé) during October, November, and December 2011. Eight Chilota and six Suffolk Down 2-month-old lambs, uncastrated males, no twin, were located to graze a typical secondary succession of the Chiloé Archipelago, as a Calafatal (a secondary succession which derivates from human intervention on native forest in Chiloé Archipelago). Simultaneously, eight male 2-month-old Chilota lambs were located to graze a naturalized pasture, another secondary succession derived from human intervention on native forest in Chiloé Archipelago. Animals had free access to water sources. Measurements were performed one time a month, for three consecutive months for productive indicators: live weight, average daily gain and body condition score, and blood indicators of protein and energetic metabolism. Productive and metabolic response was similar between both types of pastures (P > 0.05). However, Chilota and Suffolk Down lambs grazing Calafatal showed higher plasma concentrations of βOH-butyrate, but lower non-esterified fatty acids (NEFA) than Chilota lambs grazing naturalized pasture (P < 0.05). Chilota lambs grazing naturalized pasture showed the highest plasma concentrations of NEFA and urea (P < 0.05). It was concluded that, under the conditions of the study, Chilota lambs grazing naturalized pasture, which had higher contents of crude protein and metabolizable energy, showed better metabolic balance, but not performance, than Chilota and Suffolk Down lambs grazing Calafatal.

  6. Association between Metabolite Profiles, Metabolic Syndrome and Obesity Status

    PubMed Central

    Allam-Ndoul, Bénédicte; Guénard, Frédéric; Garneau, Véronique; Cormier, Hubert; Barbier, Olivier; Pérusse, Louis; Vohl, Marie-Claude

    2016-01-01

    Underlying mechanisms associated with the development of abnormal metabolic phenotypes among obese individuals are not yet clear. Our aim is to investigate differences in plasma metabolomics profiles between normal weight (NW) and overweight/obese (Ov/Ob) individuals, with or without metabolic syndrome (MetS). Mass spectrometry-based metabolite profiling was used to compare metabolite levels between each group. Three main principal components factors explaining a maximum of variance were retained. Factor 1’s (long chain glycerophospholipids) metabolite profile score was higher among Ov/Ob with MetS than among Ov/Ob and NW participants without MetS. This factor was positively correlated to plasma total cholesterol (total-C) and triglyceride levels in the three groups, to high density lipoprotein -cholesterol (HDL-C) among participants without MetS. Factor 2 (amino acids and short to long chain acylcarnitine) was positively correlated to HDL-C and negatively correlated with insulin levels among NW participants. Factor 3’s (medium chain acylcarnitines) metabolite profile scores were higher among NW participants than among Ov/Ob with or without MetS. Factor 3 was negatively associated with glucose levels among the Ov/Ob with MetS. Factor 1 seems to be associated with a deteriorated metabolic profile that corresponds to obesity, whereas Factors 2 and 3 seem to be rather associated with a healthy metabolic profile. PMID:27240400

  7. Fragment recruitment on metabolic pathways: comparative metabolic profiling of metagenomes and metatranscriptomes.

    PubMed

    Desai, Dhwani K; Schunck, Harald; Löser, Johannes W; Laroche, Julie

    2013-03-15

    The sheer scale of the metagenomic and metatranscriptomic datasets that are now available warrants the development of automated protocols for organizing, annotating and comparing the samples in terms of their metabolic profiles. We describe a user-friendly java program FROMP (Fragment Recruitment on Metabolic Pathways) for mapping and visualizing enzyme annotations onto the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways or custom-made pathways and comparing the samples in terms of their Pathway Completeness Scores, their relative Activity Scores or enzyme enrichment odds ratios. This program along with our fully configurable PERL-based annotation organization pipeline Meta2Pro (METAbolic PROfiling of META-omic data) offers a quick and accurate standalone solution for metabolic profiling of environmental samples or cultures from different treatments. Apart from pictorial comparisons, FROMP can also generate score matrices for multiple meta-omics samples, which can be used directly by other statistical programs.

  8. Methods in DNA methylation profiling

    PubMed Central

    Zuo, Tao; Tycko, Benjamin; Liu, Ta-Ming; Lin, Huey-Jen L; Huang, Tim H-M

    2010-01-01

    Metastable and somatically heritable patterns of DNA methylation provide an important level of genomic regulation. In this article, we review methods for analyzing these genome-wide epigenetic patterns and offer a perspective on the ever-expanding literature, which we hope will be useful for investigators who are new to this area. The historical aspects that we cover will be helpful in interpreting this literature and we hope that our discussion of the newest analytical methods will stimulate future progress. We emphasize that no single approach can provide a complete view of the overall methylome, and that combinations of several modalities applied to the same sample set will give the clearest picture. Given the unexpected epigenomic patterns and new biological principles, as well as new disease markers, that have been uncovered in recent studies, it is likely that important discoveries will continue to be made using genome-wide DNA methylation profiling. PMID:20526417

  9. Methods in DNA methylation profiling.

    PubMed

    Zuo, Tao; Tycko, Benjamin; Liu, Ta-Ming; Lin, Juey-Jen L; Huang, Tim H-M

    2009-12-01

    Metastable and somatically heritable patterns of DNA methylation provide an important level of genomic regulation. In this article, we review methods for analyzing these genome-wide epigenetic patterns and offer a perspective on the ever-expanding literature, which we hope will be useful for investigators who are new to this area. The historical aspects that we cover will be helpful in interpreting this literature and we hope that our discussion of the newest analytical methods will stimulate future progress. We emphasize that no single approach can provide a complete view of the overall methylome, and that combinations of several modalities applied to the same sample set will give the clearest picture. Given the unexpected epigenomic patterns and new biological principles, as well as new disease markers, that have been uncovered in recent studies, it is likely that important discoveries will continue to be made using genome-wide DNA methylation profiling.

  10. Molecular Identification, Enzyme Assay, and Metabolic Profiling of Trichoderma spp.

    PubMed

    Bae, Soo-Jung; Park, Young-Hwan; Bae, Hyeun-Jong; Jeon, Junhyun; Bae, Hanhong

    2017-06-28

    The goal of this study was to identify and characterize selected Trichoderma isolates by metabolic profiling and enzyme assay for evaluation of their potential as biocontrol agents against plant pathogens. Trichoderma isolates were obtained from the Rural Development Administration Genebank Information Center (Wanju, Republic of Korea). Eleven Trichoderma isolates were re-identified using ribosomal DNA internal transcribed spacer (ITS) regions. ITS sequence results showed new identification of Trichoderma isolates. In addition, metabolic profiling of the ethyl acetate extracts of the liquid cultures of five Trichoderma isolates that showed the best anti-Phytophthora activities was conducted using gas chromatography-mass spectrometry. Metabolic profiling revealed that Trichoderma isolates shared common metabolites with well-known antifungal activities. Enzyme assays indicated strong cell walldegrading enzyme activities of Trichoderma isolates. Overall, our results indicated that the selected Trichoderma isolates have great potential for use as biocontrol agents against plant pathogens.

  11. Metabolic profile and safety of piperlongumine

    PubMed Central

    de Lima Moreira, Fernanda; Habenschus, Maísa D.; Barth, Thiago; Marques, Lucas M. M.; Pilon, Alan Cesar; da Silva Bolzani, Vanderlan; Vessecchi, Ricardo; Lopes, Norberto P.; de Oliveira, Anderson R. M.

    2016-01-01

    Piperlongumine (PPL), a natural plant product, has been extensively studied in cancer treatment going up on clinical trials. Since the first report related to its use on cancer research (in 2011) around 80 papers have been published in less than 10 years, but a gap still remaining. There are no metabolism studies of PPL in human organism. For the lack of a better view, here, the CYP450 in vitro oxidation of PPL was described for the first time. In addition, the enzymatic kinetic data, the predicted in vivo parameters, the produced metabolites, the phenotyping study and possible piperlongumine-drug interactions in vivo is presented. PMID:27681015

  12. Serum metabolic profiles of pregnant women with burdened obstetrical history.

    PubMed

    Khaustova, S A; Senyavina, N V; Tonevitsky, A G; Eremina, O V; Pavlovich, S V

    2013-11-01

    The content of low-molecular-weight components in blood serum was studied by tandem mass-spectrometry in pregnant women. Serum metabolic profiles of patients with a grave obstetrical history were detected. The most significant changes were observed for the concentrations of low-molecular-weight substances involved in glucogenesis and β-oxidation processes and in metabolic chains involving carbohydrates, carnitines, amino acids, and lipids.

  13. Plasma Metabolic Profiles in Women are Menopause Dependent.

    PubMed

    Ke, Chaofu; Hou, Yan; Zhang, Haiyu; Yang, Kai; Wang, Jingtao; Guo, Bing; Zhang, Fan; Li, Hailong; Zhou, Xiaohua; Li, Ying; Li, Kang

    2015-01-01

    Menopause is an endocrinological transition that greatly affects health and disease susceptibility in middle-aged and elderly women. To gain new insights into the metabolic process of menopause, plasma metabolic profiles in 115 pre- and post-menopausal women were systematically analyzed by ultra-performance liquid chromatography/mass spectrometry in conjunction with univariate and multivariate statistical analysis. Metabolic signatures revealed considerable differences between pre- and post-menopausal women, and clear separations were observed between the groups in partial least-squares discriminant analysis score plots. In total, 28 metabolites were identified as potential metabolite markers for menopause, including up-regulated acylcarnitines, fatty acids, lysophosphatidylcholines, lysophosphatidylethanolamines, and down-regulated pregnanediol-3-glucuronide, dehydroepiandrosterone sulfate, p-hydroxyphenylacetic acid and dihydrolipoic acid. These differences highlight that significant alterations occur in fatty acid β-oxidation, phospholipid metabolism, hormone metabolism and amino acid metabolism in post-menopausal women. In conclusion, our plasma metabolomics study provides novel understanding of the metabolic profiles related to menopause, and will be useful for investigating menopause-related diseases and assessing metabolomic confounding factors.

  14. Metabolic Risk Profile and Cancer in Korean Men and Women.

    PubMed

    Ko, Seulki; Yoon, Seok-Jun; Kim, Dongwoo; Kim, A-Rim; Kim, Eun-Jung; Seo, Hye-Young

    2016-05-01

    Metabolic syndrome is a cluster of risk factors for type 2 diabetes mellitus and cardiovascular disease. Associations between metabolic syndrome and several types of cancer have recently been documented. We analyzed the sample cohort data from the Korean National Health Insurance Service from 2002, with a follow-up period extending to 2013. The cohort data included 99 565 individuals who participated in the health examination program and whose data were therefore present in the cohort database. The metabolic risk profile of each participant was assessed based on obesity, high serum glucose and total cholesterol levels, and high blood pressure. The occurrence of cancer was identified using Korean National Health Insurance claims data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for age group, smoking status, alcohol intake, and regular exercise. A total of 5937 cases of cancer occurred during a mean follow-up period of 10.4 years. In men with a high-risk metabolic profile, the risk of colon cancer was elevated (HR, 1.40; 95% CI, 1.14 to 1.71). In women, a high-risk metabolic profile was associated with a significantly increased risk of gallbladder and biliary tract cancer (HR, 2.05; 95% CI, 1.24 to 3.42). Non-significantly increased risks were observed in men for pharynx, larynx, rectum, and kidney cancer, and in women for colon, liver, breast, and ovarian cancer. The findings of this study support the previously suggested association between metabolic syndrome and the risk of several cancers. A high-risk metabolic profile may be an important risk factor for colon cancer in Korean men and gallbladder and biliary tract cancer in Korean women.

  15. Evaluating metabolic response to light exposure in Lactobacillus species via targeted metabolic profiling.

    PubMed

    Xu, Mengyang; Zhong, Fanyi; Zhu, Jiangjiang

    2017-02-01

    This study reported metabolic profiles of three representative strains from Lactobacillus species, and explored their metabolic response to visible light exposure. We utilized strains from three Lactobacillus species, Lactobacillus acidophilus, Lactobacillus fermentum and Lactobacillus delbrueckii as our model bacteria and applied mass spectrometry base targeted metabolomics to specifically investigate 221 metabolites within multiple metabolic pathways. Similar and diverse metabolome from three tested strains were discovered. Furthermore, all three Lactobacillus strains demonstrated different metabolic profiles in comparison between light expose verse control. In all three strains, 12 metabolites were detected to have significant differences (p-value<0.01) in light exposure culture compared to the control samples (culture grown without light exposure). Principal components analysis using these significantly changed metabolites clearly separated the exposure and control groups in all three studied Lactobacillus strains. Additionally, metabolic pathway impact analysis indicated that several commonly impacted pathways can be observed.

  16. Pathway Activity Profiling (PAPi): from the metabolite profile to the metabolic pathway activity.

    PubMed

    Aggio, Raphael B M; Ruggiero, Katya; Villas-Bôas, Silas Granato

    2010-12-01

    Metabolomics is one of the most recent omics-technologies and uses robust analytical techniques to screen low molecular mass metabolites in biological samples. It has evolved very quickly during the last decade. However, metabolomics datasets are considered highly complex when used to relate metabolite levels to metabolic pathway activity. Despite recent developments in bioinformatics, which have improved the quality of metabolomics data, there is still no straightforward method capable of correlating metabolite level to the activity of different metabolic pathways operating within the cells. Thus, this kind of analysis still depends on extremely laborious and time-consuming processes. Here, we present a new algorithm Pathway Activity Profiling (PAPi) with which we are able to compare metabolic pathway activities from metabolite profiles. The applicability and potential of PAPi was demonstrated using a previously published data from the yeast Saccharomyces cerevisiae. PAPi was able to support the biological interpretations of the previously published observations and, in addition, generated new hypotheses in a straightforward manner. However, PAPi is time consuming to perform manually. Thus, we also present here a new R-software package (PAPi) which implements the PAPi algorithm and facilitates its usage to quickly compare metabolic pathways activities between different experimental conditions. Using the identified metabolites and their respective abundances as input, the PAPi package calculates pathways' Activity Scores, which represents the potential metabolic pathways activities and allows their comparison between conditions. PAPi also performs principal components analysis and analysis of variance or t-test to investigate differences in activity level between experimental conditions. In addition, PAPi generates comparative graphs highlighting up- and down-regulated pathway activity. These datasets are available in http://www.4shared

  17. Expression profiling and comparative sequence derived insights into lipid metabolism

    SciTech Connect

    Callow, Matthew J.; Rubin, Edward M.

    2001-12-19

    Expression profiling and genomic DNA sequence comparisons are increasingly being applied to the identification and analysis of the genes involved in lipid metabolism. Not only has genome-wide expression profiling aided in the identification of novel genes involved in important processes in lipid metabolism such as sterol efflux, but the utilization of information from these studies has added to our understanding of the regulation of pathways participating in the process. Coupled with these gene expression studies, cross species comparison, searching for sequences conserved through evolution, has proven to be a powerful tool to identify important non-coding regulatory sequences as well as the discovery of novel genes relevant to lipid biology. An example of the value of this approach was the recent chance discovery of a new apolipoprotein gene (apo AV) that has dramatic effects upon triglyceride metabolism in mice and humans.

  18. Metabolic routes along digestive system of licorice: multicomponent sequential metabolism method in rat.

    PubMed

    Zhang, Lei; Zhao, Haiyu; Liu, Yang; Dong, Honghuan; Lv, Beiran; Fang, Min; Zhao, Huihui

    2016-06-01

    This study was conducted to establish the multicomponent sequential metabolism (MSM) method based on comparative analysis along the digestive system following oral administration of licorice (Glycyrrhiza uralensis Fisch., leguminosae), a traditional Chinese medicine widely used for harmonizing other ingredients in a formulae. The licorice water extract (LWE) dissolved in Krebs-Ringer buffer solution (1 g/mL) was used to carry out the experiments and the comparative analysis was performed using HPLC and LC-MS/MS methods. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to measure the LWE metabolic profile along the digestive system. The incubation experiment showed that the LWE was basically stable in digestive juice. A comparative analysis presented the metabolic profile of each prototype and its corresponding metabolites then. Liver was the major metabolic organ for LWE, and the metabolism by the intestinal flora and gut wall was also an important part of the process. The MSM method was practical and could be a potential method to describe the metabolic routes of multiple components before absorption into the systemic blood stream. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  19. Optimized Sample Handling Strategy for Metabolic Profiling of Human Feces.

    PubMed

    Gratton, Jasmine; Phetcharaburanin, Jutarop; Mullish, Benjamin H; Williams, Horace R T; Thursz, Mark; Nicholson, Jeremy K; Holmes, Elaine; Marchesi, Julian R; Li, Jia V

    2016-05-03

    Fecal metabolites are being increasingly studied to unravel the host-gut microbial metabolic interactions. However, there are currently no guidelines for fecal sample collection and storage based on a systematic evaluation of the effect of time, storage temperature, storage duration, and sampling strategy. Here we derive an optimized protocol for fecal sample handling with the aim of maximizing metabolic stability and minimizing sample degradation. Samples obtained from five healthy individuals were analyzed to assess topographical homogeneity of feces and to evaluate storage duration-, temperature-, and freeze-thaw cycle-induced metabolic changes in crude stool and fecal water using a (1)H NMR spectroscopy-based metabolic profiling approach. Interindividual variation was much greater than that attributable to storage conditions. Individual stool samples were found to be heterogeneous and spot sampling resulted in a high degree of metabolic variation. Crude fecal samples were remarkably unstable over time and exhibited distinct metabolic profiles at different storage temperatures. Microbial fermentation was the dominant driver in time-related changes observed in fecal samples stored at room temperature and this fermentative process was reduced when stored at 4 °C. Crude fecal samples frozen at -20 °C manifested elevated amino acids and nicotinate and depleted short chain fatty acids compared to crude fecal control samples. The relative concentrations of branched-chain and aromatic amino acids significantly increased in the freeze-thawed crude fecal samples, suggesting a release of microbial intracellular contents. The metabolic profiles of fecal water samples were more stable compared to crude samples. Our recommendation is that intact fecal samples should be collected, kept at 4 °C or on ice during transportation, and extracted ideally within 1 h of collection, or a maximum of 24 h. Fecal water samples should be extracted from a representative amount (∼15 g

  20. Supplementation of zilpaterol hydrochloride does not significantly alter the serum metabolic profile and metabolic enzyme profile of finishing heifers

    USDA-ARS?s Scientific Manuscript database

    Supplementation of zilpaterol hydrochloride (ZH; Zilmax®) to cattle has been implicated as having a negative impact on the well-being of cattle. However, there is no data to support or refute these claims. This study was designed to determine if differences exist in the serum metabolic profile and m...

  1. Metabolic engineering of Saccharomyces cerevisiae to improve succinic acid production based on metabolic profiling.

    PubMed

    Ito, Yuma; Hirasawa, Takashi; Shimizu, Hiroshi

    2014-01-01

    We performed metabolic engineering on the budding yeast Saccharomyces cerevisiae for enhanced production of succinic acid. Aerobic succinic acid production in S. cerevisiae was achieved by disrupting the SDH1 and SDH2 genes, which encode the catalytic subunits of succinic acid dehydrogenase. Increased succinic acid production was achieved by eliminating the ethanol biosynthesis pathways. Metabolic profiling analysis revealed that succinic acid accumulated intracellularly following disruption of the SDH1 and SDH2 genes, which suggests that enhancing the export of intracellular succinic acid outside of cells increases succinic acid production in S. cerevisiae. The mae1 gene encoding the Schizosaccharomyces pombe malic acid transporter was introduced into S. cerevisiae, and as a result, succinic acid production was successfully improved. Metabolic profiling analysis is useful in producing chemicals for metabolic engineering of microorganisms.

  2. Global urinary metabolic profiling procedures using gas chromatography-mass spectrometry.

    PubMed

    Chan, Eric Chun Yong; Pasikanti, Kishore Kumar; Nicholson, Jeremy K

    2011-09-08

    The role of urinary metabolic profiling in systems biology research is expanding. This is because of the use of this technology for clinical diagnostic and mechanistic studies and for the development of new personalized health care and molecular epidemiology (population) studies. The methodologies commonly used for metabolic profiling are NMR spectroscopy, liquid chromatography mass spectrometry (LC/MS) and gas chromatography-mass spectrometry (GC/MS). In this protocol, we describe urine collection and storage, GC/MS and data preprocessing methods, chemometric data analysis and urinary marker metabolite identification. Results obtained using GC/MS are complementary to NMR and LC/MS. Sample preparation for GC/MS analysis involves the depletion of urea via treatment with urease, protein precipitation with methanol, and trimethylsilyl derivatization. The protocol described here facilitates the metabolic profiling of ∼400-600 metabolites in 120 urine samples per week.

  3. Profiling of plasma metabolites in postmenopausal women with metabolic syndrome

    PubMed Central

    Iida, Miho; Harada, Sei; Kurihara, Ayako; Fukai, Kota; Kuwabara, Kazuyo; Sugiyama, Daisuke; Takeuchi, Ayano; Okamura, Tomonori; Akiyama, Miki; Nishiwaki, Yuji; Suzuki, Asako; Hirayama, Akiyoshi; Sugimoto, Masahiro; Soga, Tomoyoshi; Tomita, Masaru; Banno, Kouji; Aoki, Daisuke; Takebayashi, Toru

    2016-01-01

    Abstract Objective: The aim of the study was to investigate the associations of amino acids and other polar metabolites with metabolic syndrome (MetS) in postmenopausal women in a lean Asian population. Methods: The participants were 1,422 female residents enrolled in a cohort study from April to August 2012. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III modified for Japanese women. Associations were examined between MetS and 78 metabolites assayed in fasting plasma samples using capillary electrophoresis-mass spectrometry. Replication analysis was performed to confirm the robustness of the results in a separate population created by random allocation. Results: Analysis was performed for 877 naturally postmenopausal women, including 594 in the original population and 283 in the replication population. The average age, body mass index, and levels of high- and low-density lipoprotein cholesterol of the entire population were 64.6 years, 23.0 kg/m2, 72.1 mg/dL, and 126.1 mg/dL, respectively. There was no significant difference in low-density lipoprotein cholesterol levels between women with and without MetS. Thirteen metabolites were significantly related to MetS: multiple plasma amino acids were elevated in women with MetS, including branched-chain amino acids, alanine, glutamate, and proline; and alpha-aminoadipate, which is generated by lysine degradation, was also significantly increased. Conclusions: Our large-scale metabolomic profiling indicates that Japanese postmenopausal women with MetS have abnormal polar metabolites, suggesting altered catabolic pathways. These results may help to understand metabolic disturbance, including in persons with normal body mass index and relatively high levels of high-density lipoprotein cholesterol, and may have clinical utility based on further studies. PMID:27070805

  4. Metabolic profile at first-time schizophrenia diagnosis: a population-based cross-sectional study

    PubMed Central

    Horsdal, Henriette Thisted; Benros, Michael Eriksen; Köhler-Forsberg, Ole; Krogh, Jesper; Gasse, Christiane

    2017-01-01

    Objective Schizophrenia and/or antipsychotic drug use are associated with metabolic abnormalities; however, knowledge regarding metabolic status and physician’s monitoring of metabolic status at first schizophrenia diagnosis is sparse. We assessed the prevalence of monitoring for metabolic blood abnormalities and characterized the metabolic profiles in people with a first-time schizophrenia diagnosis. Methods This is a population-based cross-sectional study including all adults born in Denmark after January 1, 1955, with their first schizophrenia diagnosis between 2000 and 2012 in the Central Denmark Region. Information on metabolic parameters was obtained from a clinical laboratory information system. Associations were calculated using Wilcoxon rank-sum tests, chi-square tests, logistic regression, and Spearman’s correlation coefficients. Results A total of 2,452 people with a first-time schizophrenia diagnosis were identified, of whom 1,040 (42.4%) were monitored for metabolic abnormalities. Among those monitored, 58.4% had an abnormal lipid profile and 13.8% had an abnormal glucose profile. People who had previously filled prescription(s) for antipsychotic drugs were more likely to present an abnormal lipid measure (65.7% vs 46.8%, P<0.001) and abnormal glucose profile (16.4% vs 10.1%, P=0.01). Conclusion Metabolic abnormalities are common at first schizophrenia diagnosis, particularly among those with previous antipsychotic prescription(s). Increased metabolic abnormalities already present in the early phase of schizophrenia emphasize the need for increased monitoring and management. PMID:28280344

  5. Metabolic profiling of pregnancy: cross-sectional and longitudinal evidence.

    PubMed

    Wang, Qin; Würtz, Peter; Auro, Kirsi; Mäkinen, Ville-Petteri; Kangas, Antti J; Soininen, Pasi; Tiainen, Mika; Tynkkynen, Tuulia; Jokelainen, Jari; Santalahti, Kristiina; Salmi, Marko; Blankenberg, Stefan; Zeller, Tanja; Viikari, Jorma; Kähönen, Mika; Lehtimäki, Terho; Salomaa, Veikko; Perola, Markus; Jalkanen, Sirpa; Järvelin, Marjo-Riitta; Raitakari, Olli T; Kettunen, Johannes; Lawlor, Debbie A; Ala-Korpela, Mika

    2016-12-13

    Pregnancy triggers well-known alterations in maternal glucose and lipid balance but its overall effects on systemic metabolism remain incompletely understood. Detailed molecular profiles (87 metabolic measures and 37 cytokines) were measured for up to 4260 women (24-49 years, 322 pregnant) from three population-based cohorts in Finland. Circulating molecular concentrations in pregnant women were compared to those in non-pregnant women. Metabolic profiles were also reassessed for 583 women 6 years later to uncover the longitudinal metabolic changes in response to change in the pregnancy status. Compared to non-pregnant women, all lipoprotein subclasses and lipids were markedly increased in pregnant women. The most pronounced differences were observed for the intermediate-density, low-density and high-density lipoprotein triglyceride concentrations. Large differences were also seen for many fatty acids and amino acids. Pregnant women also had higher concentrations of low-grade inflammatory marker glycoprotein acetyls, higher concentrations of interleukin-18 and lower concentrations of interleukin-12p70. The changes in metabolic concentrations for women who were not pregnant at baseline but pregnant 6 years later (or vice versa) matched (or were mirror-images of) the cross-sectional association pattern. Cross-sectional results were consistent across the three cohorts and similar longitudinal changes were seen for 653 women in 4-year and 497 women in 10-year follow-up. For multiple metabolic measures, the changes increased in magnitude across the three trimesters. Pregnancy initiates substantial metabolic and inflammatory changes in the mothers. Comprehensive characterisation of normal pregnancy is important for gaining understanding of the key nutrients for fetal growth and development. These findings also provide a valuable molecular reference in relation to studies of adverse pregnancy outcomes.

  6. Effect of Genome and Environment on Metabolic and Inflammatory Profiles

    PubMed Central

    Sundar, Purnima; Pitts, Steven J.; Potluri, Shobha; Prifti, Edi; Kennedy, Sean; Ehrlich, S. Dusko; Neuteboom, Jacoline; Kluft, Cornelis; Malone, Karen E.; Cox, David R.; de Geus, Eco J. C.; Boomsma, Dorret I.

    2015-01-01

    Twin and family studies have established the contribution of genetic factors to variation in metabolic, hematologic and immunological parameters. The majority of these studies analyzed single or combined traits into pre-defined syndromes. In the present study, we explore an alternative multivariate approach in which a broad range of metabolic, hematologic, and immunological traits are analyzed simultaneously to determine the resemblance of monozygotic (MZ) twin pairs, twin-spouse pairs and unrelated, non-cohabiting individuals. A total of 517 participants from the Netherlands Twin Register, including 210 MZ twin pairs and 64 twin-spouse pairs, took part in the study. Data were collected on body composition, blood pressure, heart rate, and multiple biomarkers assessed in fasting blood samples, including lipid levels, glucose, insulin, liver enzymes, hematological measurements and cytokine levels. For all 51 measured traits, pair-wise Pearson correlations, correcting for family relatedness, were calculated across all the individuals in the cohort. Hierarchical clustering techniques were applied to group the measured traits into sub-clusters based on similarity. Sub-clusters were observed among metabolic traits and among inflammatory markers. We defined a phenotypic profile as the collection of all the traits measured for a given individual. Average within-pair similarity of phenotypic profiles was determined for the groups of MZ twin pairs, spouse pairs and pairs of unrelated individuals. The average similarity across the full phenotypic profile was higher for MZ twin pairs than for spouse pairs, and lowest for pairs of unrelated individuals. Cohabiting MZ twins were more similar in their phenotypic profile compared to MZ twins who no longer lived together. The correspondence in the phenotypic profile is therefore determined to a large degree by familial, mostly genetic, factors, while household factors contribute to a lesser degree to profile similarity. PMID

  7. Review of methods to probe single cell metabolism and bioenergetics

    PubMed Central

    Vasdekis, Andreas E.; Stephanopoulos, Gregory

    2015-01-01

    Single cell investigations have enabled unexpected discoveries, such as the existence of biological noise and phenotypic switching in infection, metabolism and treatment. Herein, we review methods that enable such single cell investigations specific to metabolism and bioenergetics. Firstly, we discuss how to isolate and immobilize individuals from a cell suspension, including both permanent and reversible approaches. We also highlight specific advances in microbiology for its implications in metabolic engineering. Methods for probing single cell physiology and metabolism are subsequently reviewed. The primary focus therein is on dynamic and high-content profiling strategies based on label-free and fluorescence microspectroscopy and microscopy. Non-dynamic approaches, such as mass spectrometry and nuclear magnetic resonance, are also briefly discussed. PMID:25448400

  8. Metabolic Model-Based Integration of Microbiome Taxonomic and Metabolomic Profiles Elucidates Mechanistic Links between Ecological and Metabolic Variation

    SciTech Connect

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

    2015-12-22

    ABSTRACT

    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-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 contributing to the shifts. Focusing on two independent vaginal microbiome data sets, 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 contribute significantly to these predictions. Interestingly, our analysis also detects metabolites for which the predicted variation negatively correlates with the measured variation, suggesting environmental control points of community metabolism. Applying this framework to gut microbiome data sets reveals similar trends, including prediction of bile acid metabolite shifts. This framework is an important first step toward a system-level multi-omic integration and an improved mechanistic understanding of the microbiome activity and dynamics in

  9. Metabolic Model-Based Integration of Microbiome Taxonomic and Metabolomic Profiles Elucidates Mechanistic Links between Ecological and Metabolic Variation

    PubMed Central

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

    2016-01-01

    ABSTRACT 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-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 contributing to the shifts. Focusing on two independent vaginal microbiome data sets, 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 contribute significantly to these predictions. Interestingly, our analysis also detects metabolites for which the predicted variation negatively correlates with the measured variation, suggesting environmental control points of community metabolism. Applying this framework to gut microbiome data sets reveals similar trends, including prediction of bile acid metabolite shifts. This framework is an important first step toward a system-level multi-omic integration and an improved mechanistic understanding of the microbiome activity and dynamics in health and disease

  10. Metabolic profiling distinguishes three subtypes of Alzheimer's disease

    PubMed Central

    Bredesen, Dale E.

    2015-01-01

    The cause of Alzheimer's disease is incompletely defined, and no truly effective therapy exists. However, multiple studies have implicated metabolic abnormalities such as insulin resistance, hormonal deficiencies, and hyperhomocysteinemia. Optimizing metabolic parameters in a comprehensive way has yielded cognitive improvement, both in symptomatic and asymptomatic individuals. Therefore, expanding the standard laboratory evaluation in patients with dementia may be revealing. Here I report that metabolic profiling reveals three Alzheimer's disease subtypes. The first is inflammatory, in which markers such as hs-CRP and globulin:albumin ratio are increased. The second type is non-inflammatory, in which these markers are not increased, but other metabolic abnormalities are present. The third type is a very distinctive clinical entity that affects relatively young individuals, extends beyond the typical Alzheimer's disease initial distribution to affect the cortex widely, is characterized by early non-amnestic features such as dyscalculia and aphasia, is often misdiagnosed or labeled atypical Alzheimer's disease, typically affects ApoE4-negative individuals, and is associated with striking zinc deficiency. Given the involvement of zinc in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling, this syndrome of Alzheimer's-plus with low zinc (APLZ) warrants further metabolic, genetic, and epigenetic characterization. PMID:26343025

  11. Integrated intracellular metabolic profiling and pathway analysis approaches reveal complex metabolic regulation by Clostridium acetobutylicum.

    PubMed

    Liu, Huanhuan; Huang, Di; Wen, Jianping

    2016-02-15

    Clostridium acetobutylicum is one of the most important butanol producing strains. However, environmental stress in the fermentation process usually leads to a lower yield, seriously hampering its industrialization. In order to systematically investigate the key intracellular metabolites that influence the strain growth and butanol production, and find out the critical regulation nodes, an integrated analysis approach has been carried out in this study. Based on the gas chromatography-mass spectrometry technology, the partial least square discriminant analysis and the pathway analysis, 40 metabolic pathways linked with 43 key metabolic nodes were identified. In-depth analysis showed that lots of amino acids metabolism promoted cell growth but exerted slight influence on butanol production, while sugar metabolism was favorable for cell growth but unfavorable for butanol synthesis. Besides, both lysine and succinic acid metabolism generated a complex effect on the whole metabolic network. Dicarboxylate metabolism exerted an indispensable role on cell growth and butanol production. Subsequently, rational feeding strategies were proposed to verify these conclusions and facilitate the butanol biosynthesis. Feeding amino acids, especially glycine and serine, could obviously improve cell growth while yeast extract, citric acid and ethylene glycol could significantly enhance both growth and butanol production. The feeding experiment confirmed that metabolic profiling combined with pathway analysis provided an accurate, reasonable and practical approach to explore the cellular metabolic activity and supplied a basis for improving butanol production. These strategies can also be extended for the production of other important bio-chemical compounds.

  12. [Metabolic profile according to leptin levels in obese patients].

    PubMed

    Feitosa, Alina C R; Mancini, Márcio C; Cercato, Cíntia; Villares, Sandra M; Halpern, Alfredo

    2007-02-01

    Increased body mass index and waist circumference are related to cardiovascular risk factors. Leptin is an adipocyte-produced hormone and regulates body weight. Leptin is directly related to body fat. To evaluate the relationship between leptin and metabolic profile in obese subjects, we studied 119 patients. Anthropometric, laboratory, body composition (by bioelectrical impedance) and co-morbidity data were collected. The analysis was performed in the female population (86.6%): average age: 42 +/- 13 years; hypertension, type 2 diabetes and grade III obesity were present in 61.9%, 20.2% and 58.3%, respectively. Leptin levels were positively related to insulin resistance (IR). HOMA-IR was related to metabolic abnormalities of IR. No differences were demonstrated between lipid profile, glycemia, body composition and tertiles of leptin corrected by fat weight. A significant difference in HOMA-IR was present when the 2nd and 3rd tertiles of leptin corrected by fat weight [3.4 (2.8-4.1) vs. 5.3 (4.1-6.5), p=0.011] were compared. In conclusion, leptin corrected by fat weight did not influence lipid profile and glycemia in moderate to severe obese women with similar percent body fat. Leptin should not be considered an independent factor affecting lipid metabolism.

  13. Functional and regulatory profiling of energy metabolism in fission yeast.

    PubMed

    Malecki, Michal; Bitton, Danny A; Rodríguez-López, Maria; Rallis, Charalampos; Calavia, Noelia Garcia; Smith, Graeme C; Bähler, Jürg

    2016-11-25

    The control of energy metabolism is fundamental for cell growth and function and anomalies in it are implicated in complex diseases and ageing. Metabolism in yeast cells can be manipulated by supplying different carbon sources: yeast grown on glucose rapidly proliferates by fermentation, analogous to tumour cells growing by aerobic glycolysis, whereas on non-fermentable carbon sources metabolism shifts towards respiration. We screened deletion libraries of fission yeast to identify over 200 genes required for respiratory growth. Growth media and auxotrophic mutants strongly influenced respiratory metabolism. Most genes uncovered in the mutant screens have not been implicated in respiration in budding yeast. We applied gene-expression profiling approaches to compare steady-state fermentative and respiratory growth and to analyse the dynamic adaptation to respiratory growth. The transcript levels of most genes functioning in energy metabolism pathways are coherently tuned, reflecting anticipated differences in metabolic flows between fermenting and respiring cells. We show that acetyl-CoA synthase, rather than citrate lyase, is essential for acetyl-CoA synthesis in fission yeast. We also investigated the transcriptional response to mitochondrial damage by genetic or chemical perturbations, defining a retrograde response that involves the concerted regulation of distinct groups of nuclear genes that may avert harm from mitochondrial malfunction. This study provides a rich framework of the genetic and regulatory basis of energy metabolism in fission yeast and beyond, and it pinpoints weaknesses of commonly used auxotroph mutants for investigating metabolism. As a model for cellular energy regulation, fission yeast provides an attractive and complementary system to budding yeast.

  14. Liver Adiposity and Metabolic Profile in Individuals with Chronic Spinal Cord Injury

    PubMed Central

    Rankin, Kathleen C.; O'Brien, Laura C.; Segal, Liron; Khan, M. Rehan

    2017-01-01

    Purpose To quantify liver adiposity using magnetic resonance imaging (MRI) and to determine its association with metabolic profile in men with spinal cord injury (SCI). Materials and Methods MRI analysis of liver adiposity by fat signal fraction (FSF) and visceral adipose tissue (VAT) was completed on twenty participants. Intravenous glucose tolerance test was conducted to measure glucose effectiveness (Sg) and insulin sensitivity (Si). Lipid panel, fasting glucose, glycated hemoglobin (HbA1c), and inflammatory cytokines were also analyzed. Results Average hepatic FSF was 3.7% ± 2.1. FSF was positively related to TG, non-HDL-C, fasting glucose, HbA1c, VAT, and tumor necrosis factor alpha (TNF-α). FSF was negatively related to Si and testosterone. FSF was positively related to VAT (r = 0.48, p = 0.032) and TNF-α (r = 0.51, p = 0.016) independent of age, level of injury (LOI), and time since injury (TSI). The associations between FSF and metabolic profile were independent of VAT. Conclusions MRI noninvasively estimated hepatic adiposity in men with chronic SCI. FSF was associated with dysfunction in metabolic profile, central adiposity, and inflammation. Importantly, liver adiposity influenced metabolic profile independently of VAT. These findings highlight the significance of quantifying liver adiposity after SCI to attenuate the development of metabolic disorders. PMID:28948164

  15. Staphylococcus aureus methicillin resistance detected by HPLC-MS/MS targeted metabolic profiling.

    PubMed

    Schelli, Katie; Rutowski, Joshua; Roubidoux, Julia; Zhu, Jiangjiang

    2017-03-15

    Recently, novel bioanalytical methods, such as NMR and mass spectrometry based metabolomics approaches, have started to show promise in providing rapid, sensitive and reproducible detection of Staphylococcus aureus antibiotic resistance. Here we performed a proof-of-concept study focused on the application of HPLC-MS/MS based targeted metabolic profiling for detecting and monitoring the bacterial metabolic profile changes in response to sub-lethal levels of methicillin exposure. One hundred seventy-seven targeted metabolites from over 20 metabolic pathways were specifically screened and one hundred and thirty metabolites from in vitro bacterial tests were confidently detected from both methicillin susceptible and methicillin resistant Staphylococcus aureus (MSSA and MRSA, respectively). The metabolic profiles can be used to distinguish the isogenic pairs of MSSA strains from MRSA strains, without or with sub-lethal levels of methicillin exposure. In addition, better separation between MSSA and MRSA strains can be achieved in the latter case using principal component analysis (PCA). Metabolite data from isogenic pairs of MSSA and MRSA strains were further compared without and with sub-lethal levels of methicillin exposure, with metabolic pathway analyses additionally performed. Both analyses suggested that the metabolic activities of MSSA strains were more susceptible to the perturbation of the sub-lethal levels of methicillin exposure compared to the MRSA strains.

  16. Metabolic profiling of livers and blood from obese Zucker rats.

    PubMed

    Serkova, Natalie J; Jackman, Matthew; Brown, Jaimi L; Liu, Tao; Hirose, Ryutaro; Roberts, John P; Maher, Jacquelyn J; Niemann, Claus U

    2006-05-01

    Obesity frequently leads to changes in fatty acid metabolism with subsequent fatty infiltration in the liver. In this study, metabolic profile of the livers and blood from lean and obese Zucker rats was established based on quantitative nuclear magnetic resonance spectroscopy (NMR) analysis. (1)H NMR on liver lipid extracts indicated significantly increased concentrations of total fatty acids and triglycerides. (31)P NMR on liver extracts revealed that obese livers have a compromised energy balance (low [ATP/ADP]) with decreased mitochondrial activity. Simultaneously, increased glycolytic activity was detected. The most pronounced differences were highly increased methionine and decreased betaine concentrations in obese animals. This suggests a significant alteration in methionine metabolism, which may be in part responsible for the development of steatosis, induction of mitochondrial dysfunction, and increased vulnerability of fatty livers to ischemia/reperfusion injury. A trend towards decreased hepatic glutathione concentrations as well as a reduced [PUFA/MUFA] ratio were present in the obese group, indicating increased oxidative stress and lipid peroxidation. In conclusion, NMR analysis on blood and liver tissue from obese Zucker rats reveals specific metabolic abnormalities in mitochondrial function and methionine metabolism, which result in a decreased hepatic energy state.

  17. Colorectal cancer detection using targeted serum metabolic profiling.

    PubMed

    Zhu, Jiangjiang; Djukovic, Danijel; Deng, Lingli; Gu, Haiwei; Himmati, Farhan; Chiorean, E Gabriela; Raftery, Daniel

    2014-09-05

    Colorectal cancer (CRC) is one of the most prevalent and deadly cancers in the world. Despite an expanding knowledge of its molecular pathogenesis during the past two decades, robust biomarkers to enable screening, surveillance, and therapy monitoring of CRC are still lacking. In this study, we present a targeted liquid chromatography-tandem mass spectrometry-based metabolic profiling approach for identifying biomarker candidates that could enable highly sensitive and specific CRC detection using human serum samples. In this targeted approach, 158 metabolites from 25 metabolic pathways of potential significance were monitored in 234 serum samples from three groups of patients (66 CRC patients, 76 polyp patients, and 92 healthy controls). Partial least-squares-discriminant analysis (PLS-DA) models were established, which proved to be powerful for distinguishing CRC patients from both healthy controls and polyp patients. Receiver operating characteristic curves generated based on these PLS-DA models showed high sensitivities (0.96 and 0.89, respectively, for differentiating CRC patients from healthy controls or polyp patients), good specificities (0.80 and 0.88), and excellent areas under the curve (0.93 and 0.95). Monte Carlo cross validation was also applied, demonstrating the robust diagnostic power of this metabolic profiling approach.

  18. Untargeted metabolic profiling of Vitis vinifera during fungal degradation.

    PubMed

    Karpe, Avinash V; Beale, David J; Morrison, Paul D; Harding, Ian H; Palombo, Enzo A

    2015-05-01

    This paper illustrates the application of an untargeted metabolic profiling analysis of winery-derived biomass degraded using four filamentous fungi (Trichoderma harzianum, Aspergillus niger, Penicillium chrysogenum and P. citrinum) and a yeast (Saccharomyces cerevisiae). Analysis of the metabolome resulted in the identification of 233 significant peak features [P < 0.05; fold change (FC) > 2 and signal-to-noise ratio >50] using gas chromatography-mass spectrometry followed by statistical chemometric analysis. Furthermore, A. niger and P. chrysogenum produced higher biomass degradation due to considerable β-glucosidase and xylanase activities. The major metabolites generated during fungal degradation which differentiated the metabolic profiles of fungi included sugars, sugar acids, organic acids and fatty acids. Although, P. chrysogenum could degrade hemicelluloses due to its high β-glucosidase and xylanase activities, it could not utilize the resultant pentoses, which A. niger and P. citrinum could do efficiently, thus indicating a need of mixed fungal culture to improve the biomass degradation. Saccharomyces cerevisiae, a non-cellulose degrader, exhibited sugar accumulation during the fermentation. Penicillium chrysogenum was observed to degrade about 2% lignin, a property not observed in other fungi. This study emphasized the differential fungal metabolic behavior and demonstrated the potential of metabolomics in optimizing degradation or manipulating pathways to increase yields of products of interest.

  19. Metabolic sequences of anaerobic fermentation on glucose-based feeding substrates based on correlation analyses of microbial and metabolite profiling.

    PubMed

    Date, Yasuhiro; Iikura, Tomohiro; Yamazawa, Akira; Moriya, Shigeharu; Kikuchi, Jun

    2012-12-07

    Degradation processes in various biomasses are managed by complex metabolic dynamics created by diverse and extensive interactions and competition in microbial communities and their environments. It is important to develop visualization methods to provide a bird's-eye view when characterizing the entire sequential metabolic process in an environmental ecosystem. Here, we describe an approach for the visualization of the metabolic sequences in anaerobic fermentation ecosystems, characterizing the entire metabolic dynamics using a combination of microbial community profiles and metabolic profiles. By evaluating their time-dependent variation, we found that microbial community profiles and metabolite production processes were characteristically affected by the feeding of different glucose-based substrates (glucose, starch, cellulose), although the compositions of the major microbial community and the metabolites detected were likely to be similar in all experiments. This combinatorial approach to variation in microbial communities and metabolic profiles was used successfully to visualize metabolic sequences in anaerobic fermentation ecosystems, in addition to mining candidate microbiota for cellulose degradation. Thus, this approach provides a powerful tool for visualizing and evaluating metabolic sequences within the biomass degradation process in an environmental ecosystem. This is the first report to visualize the entire metabolic dynamic in an anaerobic fermentation ecosystem as metabolic sequences.

  20. Metabolic profiling in colorectal cancer reveals signature metabolic shifts during tumorigenesis.

    PubMed

    Ong, Eng Shi; Zou, Li; Li, Shaoxia; Cheah, Peh Yean; Eu, Kong Weng; Ong, Choon Nam

    2010-02-10

    Colorectal cancer (CRC) arises as the consequence of progressive changes from normal epithelial cells through polyp to tumor, and thus is an useful model for studying metabolic shift. In the present study, we studied the metabolomic profiles using high analyte specific gas chromatography/mass spectrometry (GC/MS) and liquid chromatography tandem mass spectrometry (LC/MS/MS) to attain a systems-level view of the shift in metabolism in cells progressing along the path to CRC. Colonic tissues including tumor, polyps and adjacent matched normal mucosa from 26 patients with sporadic CRC from freshly isolated resections were used for this study. The metabolic profiles were obtained using GC/MS and LC/MS/MS. Our data suggest there was a distinct profile change of a wide range of metabolites from mucosa to tumor tissues. Various amino acids and lipids in the polyps and tumors were elevated, suggesting higher energy needs for increased cellular proliferation. In contrast, significant depletion of glucose and inositol in polyps revealed that glycolysis may be critical in early tumorigenesis. In addition, the accumulation of hypoxanthine and xanthine, and the decrease of uric acid concentration, suggest that the purine biosynthesis pathway could have been substituted by the salvage pathway in CRC. Further, there was a step-wise reduction of deoxycholic acid concentration from mucosa to tumors. It appears that to gain a growth advantage, cancer cells may adopt alternate metabolic pathways in tumorigenesis and this flexibility allows them to adapt and thrive in harsh environment.

  1. Application of Metabolic Profiling to Abdominal Aortic Aneurysm Research.

    PubMed

    Qureshi, Mahim I; Greco, Michele; Vorkas, Panagiotis A; Holmes, Elaine; Davies, Alun H

    2017-07-07

    Abdominal aortic aneurysm (AAA) is a complex disease posing diagnostic and therapeutic challenges. Metabonomics may aid in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis. A systematic review of the diversity and outcomes of existing AAA metabonomic research has been performed. Original research studies applying metabonomics to human aneurysmal disease are included. Seven relevant articles were identified: four studies were based on plasma/serum metabolite profiling, and three studies examined aneurysmal tissue. Aminomalonic acid, guanidinosuccinic acid, and glycerol emerge as potential plasma biomarkers of large aneurysm. Lipid profiling improves predictive models of aneurysm presence. Patterns of metabolite variation associated with AAA relate to carbohydrate and lipid metabolism. Perioperative perturbations in metabolites suggest differential systemic inflammatory responses to surgery, generating hypotheses for adjunctive perioperative therapy. Significant limitations include small study sizes, lack of correction for multiple testing false discovery rates, and single time-point sampling. Metabolic profiling carries the potential to identify biomarkers of AAA and elucidate pathways underlying aneurysmal disease. Statistically and methodologically robust studies are required for validation, addressing the hiatus in understanding mechanisms of aneurysm growth and developing effective treatment strategies.

  2. A Computational Model for the Analysis of Lipoprotein Distributions in the Mouse: Translating FPLC Profiles to Lipoprotein Metabolism

    PubMed Central

    Sips, Fianne L. P.; Tiemann, Christian A.; Oosterveer, Maaike H.; Groen, Albert K.; Hilbers, Peter A. J.; van Riel, Natal A. W.

    2014-01-01

    Disturbances of lipoprotein metabolism are recognized as indicators of cardiometabolic disease risk. Lipoprotein size and composition, measured in a lipoprotein profile, are considered to be disease risk markers. However, the measured profile is a collective result of complex metabolic interactions, which complicates the identification of changes in metabolism. In this study we aim to develop a method which quantitatively relates murine lipoprotein size, composition and concentration to the molecular mechanisms underlying lipoprotein metabolism. We introduce a computational framework which incorporates a novel kinetic model of murine lipoprotein metabolism. The model is applied to compute a distribution of plasma lipoproteins, which is then related to experimental lipoprotein profiles through the generation of an in silico lipoprotein profile. The model was first applied to profiles obtained from wild-type C57Bl/6J mice. The results provided insight into the interplay of lipoprotein production, remodelling and catabolism. Moreover, the concentration and metabolism of unmeasured lipoprotein components could be determined. The model was validated through the prediction of lipoprotein profiles of several transgenic mouse models commonly used in cardiovascular research. Finally, the framework was employed for longitudinal analysis of the profiles of C57Bl/6J mice following a pharmaceutical intervention with a liver X receptor (LXR) agonist. The multifaceted regulatory response to the administration of the compound is incompletely understood. The results explain the characteristic changes of the observed lipoprotein profile in terms of the underlying metabolic perturbation and resultant modifications of lipid fluxes in the body. The Murine Lipoprotein Profiler (MuLiP) presented here is thus a valuable tool to assess the metabolic origin of altered murine lipoprotein profiles and can be applied in preclinical research performed in mice for analysis of lipid fluxes and

  3. A computational model for the analysis of lipoprotein distributions in the mouse: translating FPLC profiles to lipoprotein metabolism.

    PubMed

    Sips, Fianne L P; Tiemann, Christian A; Oosterveer, Maaike H; Groen, Albert K; Hilbers, Peter A J; van Riel, Natal A W

    2014-05-01

    Disturbances of lipoprotein metabolism are recognized as indicators of cardiometabolic disease risk. Lipoprotein size and composition, measured in a lipoprotein profile, are considered to be disease risk markers. However, the measured profile is a collective result of complex metabolic interactions, which complicates the identification of changes in metabolism. In this study we aim to develop a method which quantitatively relates murine lipoprotein size, composition and concentration to the molecular mechanisms underlying lipoprotein metabolism. We introduce a computational framework which incorporates a novel kinetic model of murine lipoprotein metabolism. The model is applied to compute a distribution of plasma lipoproteins, which is then related to experimental lipoprotein profiles through the generation of an in silico lipoprotein profile. The model was first applied to profiles obtained from wild-type C57Bl/6J mice. The results provided insight into the interplay of lipoprotein production, remodelling and catabolism. Moreover, the concentration and metabolism of unmeasured lipoprotein components could be determined. The model was validated through the prediction of lipoprotein profiles of several transgenic mouse models commonly used in cardiovascular research. Finally, the framework was employed for longitudinal analysis of the profiles of C57Bl/6J mice following a pharmaceutical intervention with a liver X receptor (LXR) agonist. The multifaceted regulatory response to the administration of the compound is incompletely understood. The results explain the characteristic changes of the observed lipoprotein profile in terms of the underlying metabolic perturbation and resultant modifications of lipid fluxes in the body. The Murine Lipoprotein Profiler (MuLiP) presented here is thus a valuable tool to assess the metabolic origin of altered murine lipoprotein profiles and can be applied in preclinical research performed in mice for analysis of lipid fluxes and

  4. Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics.

    PubMed

    Austdal, Marie; Thomsen, Liv Cecilie Vestrheim; Tangerås, Line Haugstad; Skei, Bente; Mathew, Seema; Bjørge, Line; Austgulen, Rigmor; Bathen, Tone Frost; Iversen, Ann-Charlotte

    2015-12-01

    Preeclampsia is a heterogeneous gestational disease characterized by maternal hypertension and proteinuria, affecting 2-7% of pregnancies. The disorder is initiated by insufficient placental development, but studies characterizing the placental disease components are lacking. Our aim was to phenotype the preeclamptic placenta using high-resolution magic angle spinning nuclear magnetic resonance spectroscopy (HR-MAS MRS). Placental samples collected after delivery from women with preeclampsia (n = 19) and normotensive pregnancies (n = 15) were analyzed for metabolic biomarkers including amino acids, osmolytes, and components of the energy and phospholipid metabolism. The metabolic biomarkers were correlated to clinical characteristics and inflammatory biomarkers in the maternal sera. Principal component analysis showed inherent differences in placental metabolic profiles between preeclamptic and normotensive pregnancies. Significant differences in metabolic profiles were found between placentas from severe and non-severe preeclampsia, but not between preeclamptic pregnancies with fetal growth restricted versus normal weight neonates. The placental metabolites correlated with the placental stress marker sFlt-1 and triglycerides in maternal serum, suggesting variation in placental stress signaling between different placental phenotypes. HR-MAS MRS is a sensitive method for defining the placental disease component of preeclampsia, identifying several altered metabolic pathways. Placental HR-MAS MRS analysis may improve insight into processes affected in the preeclamptic placenta, and represents a novel long-required tool for a sensitive placental phenotyping of this heterogeneous disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Metabolic Model-Based Integration of Microbiome Taxonomic and Metabolomic Profiles Elucidates Mechanistic Links between Ecological and Metabolic Variation.

    PubMed

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

    2016-01-01

    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-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 contributing to the shifts. Focusing on two independent vaginal microbiome data sets, 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 contribute significantly to these predictions. Interestingly, our analysis also detects metabolites for which the predicted variation negatively correlates with the measured variation, suggesting environmental control points of community metabolism. Applying this framework to gut microbiome data sets reveals similar trends, including prediction of bile acid metabolite shifts. This framework is an important first step toward a system-level multi-omic integration and an improved mechanistic understanding of the microbiome activity and dynamics in health and disease.

  6. Gut microbiota composition modifies fecal metabolic profiles in mice.

    PubMed

    Zhao, Ying; Wu, Junfang; Li, Jia V; Zhou, Ning-Yi; Tang, Huiru; Wang, Yulan

    2013-06-07

    The gut microbiome is known to be extensively involved in human health and disease. In order to reveal the metabolic relationship between host and microbiome, we monitored recovery of the gut microbiota composition and fecal profiles of mice after gentamicin and/or ceftriaxone treatments. This was performed by employing (1)H nuclear magnetic resonance (NMR)-based metabonomics and denaturing gradient gel electrophoresis (DGGE) fingerprint of gut microbiota. The common features of fecal metabolites postantibiotic treatment include decreased levels of short chain fatty acids (SCFAs), amino acids and primary bile acids and increased oligosaccharides, d-pinitol, choline and secondary bile acids (deoxycholic acid). This suggests suppressed bacterial fermentation, protein degradation and enhanced gut microbial modification of bile acids. Barnesiella, Prevotella, and Alistipes levels were shown to decrease as a result of the antibiotic treatment, whereas levels of Bacteroides, Enterococcus and Erysipelotrichaceae incertae sedis, and Mycoplasma increased after gentamicin and ceftriaxone treatment. In addition, there was a strong correlation between fecal profiles and levels of Bacteroides, Barnesiella, Alistipes and Prevotella. The integration of metabonomics and gut microbiota profiling provides important information on the changes of gut microbiota and their impact on fecal profiles during the recovery after antibiotic treatment. The correlation between gut microbiota and fecal metabolites provides important information on the function of bacteria, which in turn could be important in optimizing therapeutic strategies, and developing potential microbiota-based disease preventions and therapeutic interventions.

  7. Metabolite profiling identifies pathways associated with metabolic risk in humans.

    PubMed

    Cheng, Susan; Rhee, Eugene P; Larson, Martin G; Lewis, Gregory D; McCabe, Elizabeth L; Shen, Dongxiao; Palma, Melinda J; Roberts, Lee D; Dejam, Andre; Souza, Amanda L; Deik, Amy A; Magnusson, Martin; Fox, Caroline S; O'Donnell, Christopher J; Vasan, Ramachandran S; Melander, Olle; Clish, Clary B; Gerszten, Robert E; Wang, Thomas J

    2012-05-08

    Although metabolic risk factors are known to cluster in individuals who are prone to developing diabetes mellitus and cardiovascular disease, the underlying biological mechanisms remain poorly understood. To identify pathways associated with cardiometabolic risk, we used liquid chromatography/mass spectrometry to determine the plasma concentrations of 45 distinct metabolites and to examine their relation to cardiometabolic risk in the Framingham Heart Study (FHS; n=1015) and the Malmö Diet and Cancer Study (MDC; n=746). We then interrogated significant findings in experimental models of cardiovascular and metabolic disease. We observed that metabolic risk factors (obesity, insulin resistance, high blood pressure, and dyslipidemia) were associated with multiple metabolites, including branched-chain amino acids, other hydrophobic amino acids, tryptophan breakdown products, and nucleotide metabolites. We observed strong associations of insulin resistance traits with glutamine (standardized regression coefficients, -0.04 to -0.22 per 1-SD change in log-glutamine; P<0.001), glutamate (0.05 to 0.14; P<0.001), and the glutamine-to-glutamate ratio (-0.05 to -0.20; P<0.001) in the discovery sample (FHS); similar associations were observed in the replication sample (MDC). High glutamine-to-glutamate ratio was associated with lower risk of incident diabetes mellitus in FHS (odds ratio, 0.79; adjusted P=0.03) but not in MDC. In experimental models, administration of glutamine in mice led to both increased glucose tolerance (P=0.01) and decreased blood pressure (P<0.05). Biochemical profiling identified circulating metabolites not previously associated with metabolic traits. Experimentally interrogating one of these pathways demonstrated that excess glutamine relative to glutamate, resulting from exogenous administration, is associated with reduced metabolic risk in mice.

  8. Measuring velocity profiles by the LDA method

    NASA Astrophysics Data System (ADS)

    Kamil, Šimeček; Katarína, Ratkovská

    2017-09-01

    This article describes in details an experiment, which was done by the method Laser Doppler Anemometry (LDA). The experiment used the wind tunnel in the laboratory at the Department of Power System Engineering, Faculty of Mechanical Engineering. The result of measuring was air velocity profiles in the wind tunnel in cases with or without an obstacle in the airflow. The measurements take place in three planes perpendicular to the axis of the wind tunnel in the middle of the height of the tunnel end. Because the LDA method measures the velocity only in separated points, it is necessary to use traverse systems in the direction of measuring lines to make the velocity profiles. The results of this experiment are histograms (diagrams which show numbers of particulars values of velocity) and velocity profiles (for whole lines). These velocity profiles are compared with the results of the same experiment, which was measured by the method Particle Image Velocimetry (PIV).

  9. Functional profiling methods in cancer.

    PubMed

    Dopazo, Joaquín

    2010-01-01

    The introduction of new high-throughput methodologies such as DNA microarrays constitutes a major breakthrough in cancer research. The unprecedented amount of data produced by such technologies has opened new avenues for interrogating living systems although, at the same time, it has demanded of the development of new data analytical methods as well as new strategies for testing hypotheses. A history of early successful applications in cancer boosted the use of microarrays and fostered further applications in other fields. Keeping the pace with these technologies, bioinformatics offers new solutions for data analysis and, what is more important, permits the formulation of a new class of hypotheses inspired in systems biology, more oriented to pathways or, in general, to modules of functionally related genes. Although these analytical methodologies are new, some options are already available and are discussed in this chapter.

  10. GRMD cardiac and skeletal muscle metabolism gene profiles are distinct.

    PubMed

    Markham, Larry W; Brinkmeyer-Langford, Candice L; Soslow, Jonathan H; Gupte, Manisha; Sawyer, Douglas B; Kornegay, Joe N; Galindo, Cristi L

    2017-04-08

    Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, which codes for the dystrophin protein. While progress has been made in defining the molecular basis and pathogenesis of DMD, major gaps remain in understanding mechanisms that contribute to the marked delay in cardiac compared to skeletal muscle dysfunction. To address this question, we analyzed cardiac and skeletal muscle tissue microarrays from golden retriever muscular dystrophy (GRMD) dogs, a genetically and clinically homologous model for DMD. A total of 15 dogs, 3 each GRMD and controls at 6 and 12 months plus 3 older (47-93 months) GRMD dogs, were assessed. GRMD dogs exhibited tissue- and age-specific transcriptional profiles and enriched functions in skeletal but not cardiac muscle, consistent with a "metabolic crisis" seen with DMD microarray studies. Most notably, dozens of energy production-associated molecules, including all of the TCA cycle enzymes and multiple electron transport components, were down regulated. Glycolytic and glycolysis shunt pathway-associated enzymes, such as those of the anabolic pentose phosphate pathway, were also altered, in keeping with gene expression in other forms of muscle atrophy. On the other hand, GRMD cardiac muscle genes were enriched in nucleotide metabolism and pathways that are critical for neuromuscular junction maintenance, synaptic function and conduction. These findings suggest differential metabolic dysfunction may contribute to distinct pathological phenotypes in skeletal and cardiac muscle.

  11. Metabolism as means for hypoxia adaptation: metabolic profiling and flux balance analysis

    PubMed Central

    Feala, Jacob D; Coquin, Laurence; Zhou, Dan; Haddad, Gabriel G; Paternostro, Giovanni; McCulloch, Andrew D

    2009-01-01

    Background Cellular hypoxia is a component of many diseases, but mechanisms of global hypoxic adaptation and resistance are not completely understood. Previously, a population of Drosophila flies was experimentally selected over several generations to survive a chronically hypoxic environment. NMR-based metabolomics, combined with flux-balance simulations of genome-scale metabolic networks, can generate specific hypotheses for global reaction fluxes within the cell. We applied these techniques to compare metabolic activity during acute hypoxia in muscle tissue of adapted versus "naïve" control flies. Results Metabolic profiles were gathered for adapted and control flies after exposure to acute hypoxia using 1H NMR spectroscopy. Principal Component Analysis suggested that the adapted flies are tuned to survive a specific oxygen level. Adapted flies better tolerate acute hypoxic stress, and we explored the mechanisms of this tolerance using a flux-balance model of central metabolism. In the model, adapted flies produced more ATP per glucose and created fewer protons than control flies, had lower pyruvate carboxylase flux, and had greater usage of Complex I over Complex II. Conclusion We suggest a network-level hypothesis of metabolic regulation in hypoxia-adapted flies, in which lower baseline rates of biosynthesis in adapted flies draws less anaplerotic flux, resulting in lower rates of glycolysis, less acidosis, and more efficient use of substrate during acute hypoxic stress. In addition we suggest new specific hypothesis, which were found to be consistent with existing data. PMID:19740440

  12. Surface Profiling Using the Photothermal Displacement Method

    NASA Astrophysics Data System (ADS)

    Umeda, Norihiro; Itoh, Ken-ichi

    1990-07-01

    This paper describes a surface profile measurement by the photothermal displacement method. This technique is based on the thermal expansion of a sample absorbing a pumping beam and on the change in the deflection of a reflected probe beam due to the slope of displacement. A vertical resolution of about 0.1 μm is experimentally obtained. The surface profile measurement of a Mn-Zn ferrite magnetic head is demonstrated.

  13. Earwax metabolomics: An innovative pilot metabolic profiling study for assessing metabolic changes in ewes during periparturition period.

    PubMed

    Shokry, Engy; Pereira, Julião; Marques Júnior, Jair Gonzalez; da Cunha, Paulo Henrique Jorge; Noronha Filho, Antônio Dionísio Feitosa; da Silva, Jessica Alves; Fioravanti, Maria Clorinda Soares; de Oliveira, Anselmo Elcana; Antoniosi Filho, Nelson Roberto

    2017-01-01

    Important metabolic changes occur during transition period of late pregnancy and early lactation to meet increasing energy demands of the growing fetus and for milk production. The aim of this investigation is to present an innovative and non-invasive tool using ewe earwax sample analysis to assess the metabolic profile in ewes during late pregnancy and early lactation. In this work, earwax samples were collected from 28 healthy Brazilian Santa Inês ewes divided into 3 sub-groups: 9 non-pregnant ewes, 6 pregnant ewes in the last 30 days of gestation, and 13 lactating ewes ≤ 30 days postpartum. Then, a range of metabolites including volatile organic compounds (VOC), amino acids (AA), and minerals were profiled and quantified in the samples by applying headspace gas chromatography/mass spectrometry, high performance liquid chromatography/tandem mass spectrometry, and inductively coupled plasma-optical emission spectrometry, respectively. As evident in our results, significant changes were observed in the metabolite profile of earwax between the studied groups where a remarkable elevation was detected in the levels of non-esterified fatty acids, alcohols, ketones, and hydroxy urea in the VOC profile of samples obtained from pregnant and lactating ewes. Meanwhile, a significant decrease was detected in the levels of 9 minerals and 14 AA including essential AA (leucine, phenyl alanine, lysine, isoleucine, threonine, valine), conditionally essential AA (arginine, glycine, tyrosine, proline, serine), and a non-essential AA (alanine). Multivariate analysis using robust principal component analysis and hierarchical cluster analysis was successfully applied to discriminate the three study groups using the variations of metabolites in the two stress states (pregnancy and lactation) from the healthy non-stress condition. The innovative developed method was successful in evaluating pre- and post-parturient metabolic changes using earwax and can in the future be applied to

  14. Automated method for study of drug metabolism

    NASA Technical Reports Server (NTRS)

    Furner, R. L.; Feller, D. D.

    1973-01-01

    Commercially available equipment can be modified to provide automated system for assaying drug metabolism by continuous flow-through. System includes steps and devices for mixing drug with enzyme and cofactor in the presence of pure oxygen, dialyzing resulting metabolite against buffer, and determining amount of metabolite by colorimetric method.

  15. Tandem mass spectrometry newborn screening for inborn errors of intermediary metabolism: abnormal profile interpretation.

    PubMed

    Fernández-Lainez, C; Aguilar-Lemus, J J; Vela-Amieva, M; Ibarra-González, I

    2012-01-01

    Expanded newborn screening for inherited metabolic disorders using tandem mass spectrometry was introduced in 1990's and is widely used around the world. In contrast to conventional screening methods, tandem mass spectrometry does not measure single analytes but identifies and quantifies metabolite profiles; one single blood spot analyzed provides information of about 60 metabolites including amino acids, acylcarnitines and related ratios that enable the diagnosis of approximately 50 different diseases. However, the interpretation of these profiles can become quite complex. The aim of this work is to present in an easy and practical manner a comprehensive compilation of information needed for tandem mass neonatal screening profile interpretation, and basic actions for immediate follow up of abnormal results, including the tests that are required for confirmatory purposes. Other conditions not attributable to metabolic disorders which can lead to an abnormal profile of these markers are also described as well as a series of general recommendations which would be useful for health professionals who are beginning newborn screening for inborn errors of intermediary metabolism using tandem mass spectrometry.

  16. METHOD AND APPARATUS FOR METABOLIC ASSAY

    DOEpatents

    Tolbert, B.M.; Kirk, M.R.; Baker, E.M.

    1961-09-19

    A method and instrumentation are described for producing an instuntuneous and continuous curve of the rate at which any selected carbon- containing substance is metabolized by a living subject. The substance is prepared with a known proportion of C/sup 14/ and, after administration, the C/ sup 14/ content of the subject's exhalations is continuously monitored along with the total C0/sub 2/ content thereof. The resulting data are continuously compared and displayed in graphical form to give the desired metabolic information. The invention includes specialized radiation counting means as well as means for assuring exact synchronization of the C/sup 14/ and C0/sub 2/ signals.

  17. Pathway analysis of kidney cancer using proteomics and metabolic profiling

    PubMed Central

    Perroud, Bertrand; Lee, Jinoo; Valkova, Nelly; Dhirapong, Amy; Lin, Pei-Yin; Fiehn, Oliver; Kültz, Dietmar; Weiss, Robert H

    2006-01-01

    Background Renal cell carcinoma (RCC) is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC). We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values < 2.0 E-05) in glycolysis, propanoate metabolism, pyruvate metabolism, urea cycle and arginine/proline metabolism, as well as in the non-metabolic p53 and FAS pathways. In a pilot study using random urine samples from both ccRCC and control patients, we performed metabolic profiling and found that only sorbitol, a component of an alternative glycolysis pathway, is significantly elevated at 5.4-fold in RCC patients as compared to controls. Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids

  18. Comparative metabolic profiling reveals secondary metabolites correlated with soybean salt tolerance.

    PubMed

    Wu, Wei; Zhang, Qing; Zhu, Yanming; Lam, Hon-Ming; Cai, Zongwei; Guo, Dianjing

    2008-12-10

    High-performance liquid chromatography-ultraviolet-electrospray ionization mass spectrometry (HPLC-UV-ESI-MS) and HPLC-ESI-MS(n) analysis methods were used for metabolic profiling and simultaneous identification of isoflavonoids and saponins in soybean seeds. Comparative targeted metabolic profiling revealed marked differences in the metabolite composition between salt-sensitive and salt-tolerant soybean varieties. Principle component analysis clearly demonstrated that it is possible to use secondary metabolites, for example, isoflavones and saponins, to discriminate between closely related soybean genotypes. Genistin and group B saponins were identified as the key secondary metabolites correlated with salt tolerance. These individual metabolites may provide additional insight into the salt tolerance and adaptation of plants.

  19. Olive phenolic compounds: metabolic and transcriptional profiling during fruit development

    PubMed Central

    2012-01-01

    Background Olive (Olea europaea L.) fruits contain numerous secondary metabolites, primarily phenolics, terpenes and sterols, some of which are particularly interesting for their nutraceutical properties. This study will attempt to provide further insight into the profile of olive phenolic compounds during fruit development and to identify the major genetic determinants of phenolic metabolism. Results The concentration of the major phenolic compounds, such as oleuropein, demethyloleuropein, 3–4 DHPEA-EDA, ligstroside, tyrosol, hydroxytyrosol, verbascoside and lignans, were measured in the developing fruits of 12 olive cultivars. The content of these compounds varied significantly among the cultivars and decreased during fruit development and maturation, with some compounds showing specificity for certain cultivars. Thirty-five olive transcripts homologous to genes involved in the pathways of the main secondary metabolites were identified from the massive sequencing data of the olive fruit transcriptome or from cDNA-AFLP analysis. Their mRNA levels were determined using RT-qPCR analysis on fruits of high- and low-phenolic varieties (Coratina and Dolce d’Andria, respectively) during three different fruit developmental stages. A strong correlation was observed between phenolic compound concentrations and transcripts putatively involved in their biosynthesis, suggesting a transcriptional regulation of the corresponding pathways. OeDXS, OeGES, OeGE10H and OeADH, encoding putative 1-deoxy-D-xylulose-5-P synthase, geraniol synthase, geraniol 10-hydroxylase and arogenate dehydrogenase, respectively, were almost exclusively present at 45 days after flowering (DAF), suggesting that these compounds might play a key role in regulating secoiridoid accumulation during fruit development. Conclusions Metabolic and transcriptional profiling led to the identification of some major players putatively involved in biosynthesis of secondary compounds in the olive tree. Our data

  20. Multidimensional Profiling Platforms Reveal Metabolic Dysregulation caused by Organophosphorus Pesticides

    PubMed Central

    Medina-Cleghorn, Daniel; Heslin, Ann; Morris, Patrick J.; Mulvihill, Melinda M.; Nomura, Daniel K.

    2014-01-01

    We are environmentally exposed to countless synthetic chemicals on a daily basis with an increasing number of these chemical exposures linked to adverse health effects. However, our understanding of the (patho)physiological effects of these chemicals remains poorly understood, due in-part to a general lack of effort to systematically and comprehensively identify the direct interactions of environmental chemicals with biological macromolecules in mammalian systems in vivo. Here, we have used functional chemoproteomic and metabolomic platforms to broadly identify direct enzyme targets that are inhibited by widely used organophosphorus (OP) pesticides in vivo in mice and to determine metabolic alterations that are caused by these chemicals. We find that these pesticides directly inhibit over 20 serine hydrolases in vivo leading to widespread disruptions in lipid metabolism. Through identifying direct biological targets of OP pesticides, we show heretofore unrecognized modes of toxicity that may be associated with these agents and underscore the utility of utilizing multidimensional profiling approaches to obtain a more complete understanding of toxicities associated with environmental chemicals. PMID:24205821

  1. Cardiac Autonomic Nervous System Activation and Metabolic Profile in Young Children: The ABCD Study

    PubMed Central

    Vrijkotte, Tanja G. M.; van den Born, Bert-Jan H.; Hoekstra, Christine M. C. A.; Gademan, Maaike G. J.; van Eijsden, Manon; de Rooij, Susanne R.; Twickler, Marcel T. B.

    2015-01-01

    Background In adults, increased sympathetic and decreased parasympathetic nervous system activity are associated with a less favorable metabolic profile. Whether this is already determined at early age is unknown. Therefore, we aimed to assess the association between autonomic nervous system activation and metabolic profile and its components in children at age of 5–6 years. Methods Cross-sectional data from an apparently healthy population (within the ABCD study) were collected at age 5–6 years in 1540 children. Heart rate (HR), respiratory sinus arrhythmia (RSA; parasympathetic activity) and pre-ejection period (PEP; sympathetic activity) were assessed during rest. Metabolic components were waist-height ratio (WHtR), systolic blood pressure (SBP), fasting triglycerides, glucose and HDL-cholesterol. Individual components, as well as a cumulative metabolic score, were analyzed. Results In analysis adjusted for child’s physical activity, sleep, anxiety score and other potential confounders, increased HR and decreased RSA were associated with higher WHtR (P< 0.01), higher SBP (p<0.001) and a higher cumulative metabolic score (HR: p < 0.001; RSA: p < 0.01). Lower PEP was only associated with higher SBP (p <0.05). Of all children, 5.6% had 3 or more (out of 5) adverse metabolic components; only higher HR was associated with this risk (per 10 bpm increase: OR = 1.56; p < 0.001). Conclusions This study shows that decreased parasympathetic activity is associated with central adiposity and higher SBP, indicative of increased metabolic risk, already at age 5–6 years. PMID:26394362

  2. Effects of Valproic Acid on Organic Acid Metabolism in Children: A Metabolic Profiling Study

    PubMed Central

    Price, K.E.; Pearce, R.E.; Garg, U.C.; Heese, B.A.; Smith, L.D.; Sullivan, J.E.; Kennedy, M.J.; Bale, J.F.; Ward, R.M.; Chang, T.K.H.; Abbott, Frank S.; Leeder, J.S.

    2013-01-01

    Young children are at increased risk for valproic acid (VPA) hepatotoxicity. Urinary organic acid profiles, as a measure of mitochondrial function, were obtained in children 3.5 to 17.3 years old treated for seizure disorders with valproic acid (VPA; n=52). Age-matched patients treated with carbamazepine (CBZ; n=50) and untreated healthy children (n=22) served as controls. Age-related changes in organic acid profiles were observed in all three groups. Although untreated and CBZ control subjects were not distinguished by the principal component analysis (PCA) scores plot, a distinct boundary was apparent between the VPA and control/CBZ groups. Inter-individual variability in VPA-induced alterations in endogenous pathways reflecting branched chain amino acid metabolism and oxidative stress was observed. The data suggest that more detailed metabolomic analysis may provide novel insights into biological mechanisms and predictive biomarkers for children at highest risk for serious toxicity. PMID:21544075

  3. Assessing microbial communities for a metabolic profile similar to activated sludge.

    PubMed

    Paixão, S M; Sàágua, M C; Tenreiro, R; Anselmo, A M

    2007-05-01

    To search for reliable testing inocula alternatives to activated sludge cultures, several model microbial consortia were compared with activated sludge populations for their functional diversity. The evaluation of the metabolic potential of these mixed inocula was performed using the Biolog EcoPlates and GN and GP MicroPlates (Biolog, Inc., Hayward, California). The community-level physiological profiles (CLPPs) obtained for model communities and activated sludge samples were analyzed by principal component analysis and hierarchic clustering methods, to evaluate the ability of Biolog plates to distinguish among the different microbial communities. The effect of different inocula preparation methodologies on the community structure was also studied. The CLPPs obtained with EcoPlates and GN MicroPlates showed that EcoPlates are suitable to screen communities with a metabolic profile similar to activated sludge. New, well-defined, standardized, and safe inocula presenting the same metabolic community profile as activated sludge were selected and can be tested as surrogate cultures in activated-sludge-based bioassays.

  4. Intraspecific variability in allelopathy of Heracleum mantegazzianum is linked to the metabolic profile of root exudates

    PubMed Central

    Jandová, Kateřina; Dostál, Petr; Cajthaml, Tomáš; Kameník, Zdeněk

    2015-01-01

    Background and Aims Allelopathy may drive invasions of some exotic plants, although empirical evidence for this theory remains largely inconclusive. This could be related to the large intraspecific variability of chemically mediated plant–plant interactions, which is poorly studied. This study addressed intraspecific variability in allelopathy of Heracleum mantegazzianum (giant hogweed), an invasive species with a considerable negative impact on native communities and ecosystems. Methods Bioassays were carried out to test the alleopathic effects of H. mantegazzianum root exudates on germination of Arabidopsis thaliana and Plantago lanceolata. Populations of H. mantegazzianum from the Czech Republic were sampled and variation in the phytotoxic effects of the exudates was partitioned between areas, populations within areas, and maternal lines. The composition of the root exudates was determined by metabolic profiling using ultra-high-performance liquid chromatography with time-of-flight mass spectrometry, and the relationships between the metabolic profiles and the effects observed in the bioassays were tested using orthogonal partial least-squares analysis. Key Results Variance partitioning indicated that the highest variance in phytotoxic effects was within populations. The inhibition of germination observed in the bioassay for the co-occurring native species P. lanceolata could be predicted by the metabolic profiles of the root exudates of particular maternal lines. Fifteen compounds associated with this inhibition were tentatively identified. Conclusions The results present strong evidence that intraspecific variability needs to be considered in research on allelopathy, and suggest that metabolic profiling provides an efficient tool for studying chemically mediated plant–plant interactions whenever unknown metabolites are involved. PMID:25714817

  5. Profiling human gut bacterial metabolism and its kinetics using [U-13C]glucose and NMR.

    PubMed

    de Graaf, Albert A; Maathuis, Annet; de Waard, Pieter; Deutz, Nicolaas E P; Dijkema, Cor; de Vos, Willem M; Venema, Koen

    2010-01-01

    This study introduces a stable-isotope metabolic approach employing [U-(13)C]glucose that, as a novelty, allows selective profiling of the human intestinal microbial metabolic products of carbohydrate food components, as well as the measurement of the kinetics of their formation pathways, in a single experiment. A well-established, validated in vitro model of human intestinal fermentation was inoculated with standardized gastrointestinal microbiota from volunteers. After culture stabilization, [U-(13)C]glucose was added as an isotopically labeled metabolic precursor. System lumen and dialysate samples were taken at regular intervals. Metabolite concentrations and isotopic labeling were determined by NMR, GC, and enzymatic methods. The main microbial metabolites were lactate, acetate, butyrate, formate, ethanol, and glycerol. They together accounted for a (13)C recovery rate as high as 91.2%. Using an NMR chemical shift prediction approach, several minor products that showed (13)C incorporation were identified as organic acids, amino acids, and various alcohols. Using computer modeling of the (12)C contents and (13)C labeling kinetics, the metabolic fluxes in the gut microbial pathways for synthesis of lactate, formate, acetate, and butyrate were determined separately for glucose and unlabeled background substrates. This novel approach enables the study of the modulation of human intestinal function by single nutrients, providing a new rational basis for achieving control of the short-chain fatty acids profile by manipulating substrate and microbiota composition in a purposeful manner.

  6. Metabolic Profile of Breast Cancer in a Population of Women in Southern Spain

    PubMed Central

    Lopez-Saez, Juan-Bosco; Martinez-Rubio, Jose Antonio; Alvarez, Maria Montes; Carrera, Carmen Gonzalez; Dominguez Villar, Margarita; de Lomas Mier, Antonio Garcia; Doménech, Charo; Senra-Varela, Avelino

    2008-01-01

    Background: There are indications that mortality in breast cancer is related with dietary factors, but no study has been large enough to characterise reliably how, this risk is influenced. To establish a logistic regression equation that would predict breast cancer from factors in the endocrinological and metabolic profile, we studied endocrinological and metabolic risk factors that are modified by the diet, in a population of women with breast cancer in southern Spain. Patients and Methods: We carried out a simple a case-control study comparing 204 women with breast cancer (96 premenopausal and 108 postmenopausal women) and 250 healthy control subjects. The predictive variables were basal glycaemia, insulin, glycosylated haemoglobin (HbA1c), C-peptide, insulin-like growth factor-I (IGF-I), total cholesterol, triglycerides, high density lipoprotein-c (HDL-C), low density lipoprotein-c (LDL-C), selenium and Quetelet index (BMI). Results: The metabolic profile differed between pre- and postmenopausal patients, and metabolic alterations were greater in postmenopausal than in premenopausal women. The differences between healthy subjects and breast cancer patients were clearly significant. Conclusions: Our findings have several potential practical applications in the early detection of breast cancer, especially in premenopausal women; in primary prevention; and in the development of a mathematical model of breast carcinogenesis. PMID:18665244

  7. Effect of alprazolam on rat serum metabolic profiles.

    PubMed

    Li, Yan; Lin, Gaotong; Chen, Bingbao; Zhang, Jing; Wang, Lingtian; Li, Zixia; Cao, Yungang; Wen, Congcong; Yang, Xuezhi; Cao, Gaozhong; Wang, Xianqin; Cao, Guoquan

    2017-02-10

    We developed a serum metabolomic method by gas chromatography-mass spectrometry (GC-MS) to evaluate the effect of alprazolam in rats. The GC-MS with HP-5MS (0.25 µm × 30 m × 0.25 mm), mass was conducted in EI mode with electron energy of 70 eV, full-scan mode with m/z 50-550. The rats were randomly divided to four group, three alprazolam treated group and control group. The alprazolam treated group rats were given 5, 10, 20 mg/kg (Low, Medium, High) of alprazolam by intragastric administration each day for 14 days, the serum samples were corrected on the seventh and fourteenth day for metabolomic study. The blood was collected for biochemical tests. Then liver and brain were rapidly isolated and immersed for pathological study. Compared to the control group on seventh and fourteen days, the level of d-glucose, 9,12-octadecadienoic acid, butanoic acid, L-proline, d-mannose and malic acid changed, indicating that alprazolam treated rats induced energy metabolism, fatty acid metabolism, amino acid metabolism perturbations in rats. There is no significant difference for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and uric acid (UA) between control and alprazolam group. According to the pathological results, alprazolam is not hepatotoxic. Metabolomics could distinguish different alprazolam dose in rats.

  8. A GC-MS metabolic profiling study of plasma samples from mice on low- and high-fat diets.

    PubMed

    Spagou, Konstantina; Theodoridis, Georgios; Wilson, Ian; Raikos, Nikolaos; Greaves, Peter; Edwards, Richard; Nolan, Barbara; Klapa, Maria I

    2011-05-15

    Metabolic profiling of biofluids, based on the quantitative analysis of the concentration profile of their free low molecular mass metabolites, has been playing increasing role employed as a means to gain understanding of the progression of metabolic disorders, including obesity. Chromatographic methods coupled with mass spectrometry have been established as a strategy for metabolic profiling. Among these, GC-MS, targeting mainly the primary metabolism intermediates, offers high sensitivity, good peak resolution and extensive databases. However, the derivatization step required for many involatile metabolites necessitates specific data validation, normalization and analysis protocols to ensure accurate and reproducible performance. In this study, the GC-MS metabolic profiles of plasma samples from mice maintained on 12- or 15-month long low (10 kcal%) or high (60 kcal%) fat diets were obtained. The profiles of the trimethylsilyl(TMS)-methoxime(MeOx) derivatives of the free polar metabolites were acquired through GC-(ion trap)MS, using [U-(13)C]-glucose as the internal standard. After the application of a recently developed data correction and normalization/filtering protocol for GC-MS metabolomic datasets, the profiles of 48 out of the 77 detected metabolites were used in multivariate statistical analysis. Data mining suggested a decrease in the activity of the energy metabolism with age. In addition, the metabolic profiles indicated the presence of subpopulations with different physiology within the high- and low-fat diet mice, which correlated well with the difference in body weight among the animals and current knowledge about hyperglycemic conditions. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Distributed Method to Optimal Profile Descent

    NASA Astrophysics Data System (ADS)

    Kim, Geun I.

    Current ground automation tools for Optimal Profile Descent (OPD) procedures utilize path stretching and speed profile change to maintain proper merging and spacing requirements at high traffic terminal area. However, low predictability of aircraft's vertical profile and path deviation during decent add uncertainty to computing estimated time of arrival, a key information that enables the ground control center to manage airspace traffic effectively. This paper uses an OPD procedure that is based on a constant flight path angle to increase the predictability of the vertical profile and defines an OPD optimization problem that uses both path stretching and speed profile change while largely maintaining the original OPD procedure. This problem minimizes the cumulative cost of performing OPD procedures for a group of aircraft by assigning a time cost function to each aircraft and a separation cost function to a pair of aircraft. The OPD optimization problem is then solved in a decentralized manner using dual decomposition techniques under inter-aircraft ADS-B mechanism. This method divides the optimization problem into more manageable sub-problems which are then distributed to the group of aircraft. Each aircraft solves its assigned sub-problem and communicate the solutions to other aircraft in an iterative process until an optimal solution is achieved thus decentralizing the computation of the optimization problem.

  10. Molecular subtyping of metastatic melanoma based on cell ganglioside metabolism profiles.

    PubMed

    Tringali, Cristina; Silvestri, Ilaria; Testa, Francesca; Baldassari, Paola; Anastasia, Luigi; Mortarini, Roberta; Anichini, Andrea; López-Requena, Alejandro; Tettamanti, Guido; Venerando, Bruno

    2014-08-01

    In addition to alterations concerning the expression of oncogenes and onco-suppressors, melanoma is characterized by the presence of distinctive gangliosides (sialic acid carrying glycosphingolipids). Gangliosides strongly control cell surface dynamics and signaling; therefore, it could be assumed that these alterations are linked to modifications of cell behavior acquired by the tumor. On these bases, this work investigated the correlations between melanoma cell ganglioside metabolism profiles and the biological features of the tumor and the survival of patients. Melanoma cell lines were established from surgical specimens of AJCC stage III and IV melanoma patients. Sphingolipid analysis was carried out on melanoma cell lines and melanocytes through cell metabolic labeling employing [3-3H]sphingosine and by FACS. N-glycolyl GM3 was identified employing the 14 F7 antibody. Gene expression was assayed by Real Time PCR. Cell invasiveness was assayed through a Matrigel invasion assay; cell proliferation was determined through the soft agar assay, MTT, and [3H] thymidine incorporation. Statistical analysis was performed using XLSTAT software for melanoma hierarchical clustering based on ganglioside profile, the Kaplan-Meier method, the log-rank (Mantel-Cox) test, and the Mantel-Haenszel test for survival analysis. Based on the ganglioside profiles, through a hierarchical clustering, we classified melanoma cells isolated from patients into three clusters: 1) cluster 1, characterized by high content of GM3, mainly in the form of N-glycolyl GM3, and GD3; 2) cluster 2, characterized by the appearance of complex gangliosides and by a low content of GM3; 3) cluster 3, which showed an intermediate phenotype between cluster 1 and cluster 3. Moreover, our data demonstrated that: a) a correlation could be traced between patients' survival and clusters based on ganglioside profiles, with cluster 1 showing the worst survival; b) the expression of several enzymes (sialidase NEU3

  11. Optimised protocols for the metabolic profiling of S. cerevisiae by 1H-NMR and HRMAS spectroscopy.

    PubMed

    Palomino-Schätzlein, Martina; Molina-Navarro, Maria Micaela; Tormos-Pérez, Marta; Rodríguez-Navarro, Susana; Pineda-Lucena, Antonio

    2013-10-01

    An optimised extraction protocol for the analysis of Saccharomyces cerevisiae aqueous and organic metabolites by nuclear magnetic resonance spectroscopy that allows the identification and quantification of up to 50 different compounds is presented. The method was compared with other metabolic profiling protocols for S. cerevisiae, where generally different analytical techniques are applied for metabolite quantification. In addition, the analysis of intact S. cerevisiae cells by HRMAS was implemented for the first time as a complementary method. The optimised protocols were applied to study the metabolic effect of glucose and galactose on S. cerevisiae growth. Furthermore, the metabolic reaction of S. cerevisiae to osmotic stress has been studied.

  12. Metabolic profiling reveals ethylene mediated metabolic changes and a coordinated adaptive mechanism of 'Jonagold' apple to low oxygen stress.

    PubMed

    Bekele, Elias A; Beshir, Wasiye F; Hertog, Maarten L A T M; Nicolai, Bart M; Geeraerd, Annemie H

    2015-11-01

    Apples are predominantly stored in controlled atmosphere (CA) storage to delay ripening and prolong their storage life. Profiling the dynamics of metabolic changes during ripening and CA storage is vital for understanding the governing molecular mechanism. In this study, the dynamics of the primary metabolism of 'Jonagold' apples during ripening in regular air (RA) storage and initiation of CA storage was profiled. 1-Methylcyclopropene (1-MCP) was exploited to block ethylene receptors and to get insight into ethylene mediated metabolic changes during ripening of the fruit and in response to hypoxic stress. Metabolic changes were quantified in glycolysis, the tricarboxylic acid (TCA) cycle, the Yang cycle and synthesis of the main amino acids branching from these metabolic pathways. Partial least square discriminant analysis of the metabolic profiles of 1-MCP treated and control apples revealed a metabolic divergence in ethylene, organic acid, sugar and amino acid metabolism. During RA storage at 18°C, most amino acids were higher in 1-MCP treated apples, whereas 1-aminocyclopropane-1-carboxylic acid (ACC) was higher in the control apples. The initial response of the fruit to CA initiation was accompanied by an increase of alanine, succinate and glutamate, but a decline in aspartate. Furthermore, alanine and succinate accumulated to higher levels in control apples than 1-MCP treated apples. The observed metabolic changes in these interlinked metabolites may indicate a coordinated adaptive strategy to maximize energy production.

  13. Metabolic syndrome and metabolic risk profile according to polycystic ovary syndrome phenotype.

    PubMed

    Bil, Enes; Dilbaz, Berna; Cirik, Derya Akdag; Ozelci, Runa; Ozkaya, Enis; Dilbaz, Serdar

    2016-07-01

    It is unknown which phenotype of polycystic ovary syndrome (PCOS) has a greater metabolic risk and how to detect this risk. The aim of this study was therefore to compare the incidence of metabolic syndrome (MetS) and metabolic risk profile (MRP) for different phenotypes. A total of 100 consecutive newly diagnosed PCOS women in a tertiary referral hospital were recruited. Patients were classified into four phenotypes according to the Rotterdam criteria, on the presence of at least two of the three criteria hyperandrogenism (H), oligo/anovulation (O) and PCO appearance (P): phenotype A, H + O + P; phenotype B, H + O; phenotype C, H + P; phenotype D, O + P. Prevalence of MetS and MRP were compared among the four groups. Based on Natural Cholesterol Education Program Adult Treatment Panel III diagnostic criteria, MetS prevalence was higher in phenotypes A and B (29.6% and 34.5%) compared with the other phenotypes (10.0% and 8.3%; P < 0.001). Although the prevalence of obesity was similar, the number of patients with homeostatic model assessment insulin resistance index (HOMA-IR) >3.8 was significantly higher in androgenic PCOS phenotypes. After logistic regression analysis, visceral adiposity index (VAI) was the only independent predictor of MetS in PCOS (P = 0.002). VAI was also significantly higher in phenotype B, when compared with the others (P < 0.01). Phenotypes A and B had the highest risk of MetS among the four phenotypes, and VAI may be a predictor of metabolic risk in PCOS women. © 2016 Japan Society of Obstetrics and Gynecology.

  14. Impact of early fructose intake on metabolic profile and aerobic capacity of rats

    PubMed Central

    2011-01-01

    Background Metabolic syndrome is a disease that today affects millions of people around the world. Therefore, it is of great interest to implement more effective procedures for preventing and treating this disease. In search of a suitable experimental model to study the role of exercise in prevention and treatment of metabolic syndrome, this study examined the metabolic profile and the aerobic capacity of rats kept early in life on a fructose-rich diet, a substrate that has been associated with metabolic syndrome. Methods We used adult female Wistar rats fed during pregnancy and lactation with two diets: balanced or fructose-rich 60%. During breastfeeding, the pups were distributed in small (4/mother) or adequate (8/mother) litters. At 90 days of age, they were analyzed with respect to: glucose tolerance, peripheral insulin sensitivity, aerobic capacity and serum glucose, insulin, triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol concentrations as well as measures of glycogen synthesis and glucose oxidation by the soleus muscle. Results It was found that the fructose rich diet led the animals to insulin resistance. The fructose fed rats kept in small litters also showed dyslipidemia, with increased serum concentrations of total cholesterol and triglycerides. Conclusion Neither the aerobic capacity nor the glucose oxidation rates by the skeletal muscle were altered by fructose-rich diet, indicating that the animal model evaluated is potentially interesting for the study of the role of exercise in metabolic syndrome. PMID:21223589

  15. Genetic dissection of scent metabolic profiles in diploid rose populations.

    PubMed

    Spiller, M; Berger, R G; Debener, Thomas

    2010-05-01

    The scent of flowers is a very important trait in ornamental roses in terms of both quantity and quality. In cut roses, scented varieties are a rare exception. Although metabolic profiling has identified more than 500 scent volatiles from rose flowers so far, nothing is known about the inheritance of scent in roses. Therefore, we analysed scent volatiles and molecular markers in diploid segregating populations. We resolved the patterns of inheritance of three volatiles (nerol, neryl acetate and geranyl acetate) into single Mendelian traits, and we mapped these as single or oligogenic traits in the rose genome. Three other volatiles (geraniol, beta-citronellol and 2-phenylethanol) displayed quantitative variation in the progeny, and we mapped a total of six QTLs influencing the amounts of these volatiles onto the rose marker map. Because we included known scent related genes and newly generated ESTs for scent volatiles as markers, we were able to link scent related QTLs with putative candidate genes. Our results serve as a starting point for both more detailed analyses of complex scent biosynthetic pathways and the development of markers for marker-assisted breeding of scented rose varieties.

  16. Metabolic and biological profile of autochthonous Vitis vinifera L. ecotypes.

    PubMed

    Impei, Stefania; Gismondi, Angelo; Canuti, Lorena; Canini, Antonella

    2015-05-01

    Vitis vinifera L. is a plant species rich in phenolic compounds that are usually associated with the health benefits of wine and grape consumption in the diet. Anthocyanins, catechins, flavonol, phenolic acids and stilbenes are key molecular constituents of the Vitis berries, affecting the quality of grape products. The purpose of this work was to identify the metabolic profiles of 37 genetically certified V. vinifera Latial accessions. In particular, qualitative and quantitative analyses of specific secondary metabolites and total phenolic and tannin contents were performed by LC-MS and spectrophotometric analysis. In addition, since plant molecules are well-known for their free radical scavenging properties, the antioxidant effects of the sample extracts were evaluated through two different antiradical assays: DPPH and FRAP tests. Finally, a preliminary screening of the antiproliferative activity of each specimen on HCT-116 human colorectal cancer cells was conducted. All the results showed a great variety and amount of phenolic compounds in all accessions; moreover, we observed a significant correlation in the extracts between the metabolite concentration and bioactivity. Besides, some samples presented extraordinary biological effects, such as reduction of tumor cell growth not associated with cytotoxicity, supporting their use as possible future adjuvants for cancer therapy. In conclusion, the present research increased the scientific knowledge about Italian autochthonous vine ecotypes in order to valorize them and support their reintroduction in the local economic system.

  17. Remote motor system metabolic profile and surgery outcome in cervical spondylotic myelopathy.

    PubMed

    Craciunas, Sorin C; Gorgan, Mircea R; Ianosi, Bogdan; Lee, Phil; Burris, Joseph; Cirstea, Carmen M

    2017-03-17

    OBJECTIVE In patients with cervical spondylotic myelopathy (CSM), the motor system may undergo progressive functional/structural changes rostral to the lesion, and these changes may be associated with clinical disability. The extent to which these changes have a prognostic value in the clinical recovery after surgical treatment is not yet known. In this study, magnetic resonance spectroscopy (MRS) was used to test 2 primary hypotheses. 1) Based on evidence of corticospinal and spinocerebellar, rubro-, or reticulospinal tract degeneration/dysfunction during chronic spinal cord compression, the authors hypothesized that the metabolic profile of the primary motor cortices (M1s) and cerebellum, respectively, would be altered in patients with CSM, and these alterations would be associated with the extent of the neurological disabilities. 2) Considering that damage and/or plasticity in the remote motor system may contribute to clinical recovery, they hypothesized that M1 and cerebellar metabolic profiles would predict, at least in part, surgical outcome. METHODS The metabolic profile, consisting of N-acetylaspartate (NAA; marker of neuronal integrity), myoinositol (glial marker), choline (cell membrane synthesis and turnover), and glutamate-glutamine (glutamatergic system), of the M1 hand/arm territory in each hemisphere and the cerebellum vermis was investigated prior to surgery in 21 patients exhibiting weakness of the upper extremities and/or gait abnormalities. Age- and sex-matched controls (n = 16) were also evaluated to estimate the pre-CSM metabolic profile of these areas. Correlation and regression analyses were performed between preoperative metabolite levels and clinical status 6 months after surgery. RESULTS Relative to controls, patients exhibited significantly higher levels of choline but no difference in the levels of other metabolites across M1s. Cerebellar metabolite levels were indistinguishable from control levels. Certain metabolites-myo-inositol and

  18. Inferring Carbon Sources from Gene Expression Profiles Using Metabolic Flux Models

    PubMed Central

    Ip, Kuhn; Zucker, Jeremy; Colijn, Caroline; Weiner, Brian; Galagan, James E.

    2012-01-01

    Background Bacteria have evolved the ability to efficiently and resourcefully adapt to changing environments. A key means by which they optimize their use of available nutrients is through adjustments in gene expression with consequent changes in enzyme activity. We report a new method for drawing environmental inferences from gene expression data. Our method prioritizes a list of candidate carbon sources for their compatibility with a gene expression profile using the framework of flux balance analysis to model the organism’s metabolic network. Principal Findings For each of six gene expression profiles for Escherichia coli grown under differing nutrient conditions, we applied our method to prioritize a set of eighteen different candidate carbon sources. Our method ranked the correct carbon source as one of the top three candidates for five of the six expression sets when used with a genome-scale model. The correct candidate ranked fifth in the remaining case. Additional analyses show that these rankings are robust with respect to biological and measurement variation, and depend on specific gene expression, rather than general expression level. The gene expression profiles are highly adaptive: simulated production of biomass averaged 94.84% of maximum when the in silico carbon source matched the in vitro source of the expression profile, and 65.97% when it did not. Conclusions Inferences about a microorganism’s nutrient environment can be made by integrating gene expression data into a metabolic framework. This work demonstrates that reaction flux limits for a model can be computed which are realistic in the sense that they affect in silico growth in a manner analogous to that in which a microorganism’s alteration of gene expression is adaptive to its nutrient environment. PMID:22606312

  19. Genomic and Metabolomic Profile Associated to Clustering of Cardio-Metabolic Risk Factors

    PubMed Central

    Marrachelli, Vannina G.; Rentero, Pilar; Mansego, María L.; Morales, Jose Manuel; Galan, Inma; Pardo-Tendero, Mercedes; Martinez, Fernando; Martin-Escudero, Juan Carlos; Briongos, Laisa; Chaves, Felipe Javier; Redon, Josep; Monleon, Daniel

    2016-01-01

    Background To identify metabolomic and genomic markers associated with the presence of clustering of cardiometabolic risk factors (CMRFs) from a general population. Methods and Findings One thousand five hundred and two subjects, Caucasian, > 18 years, representative of the general population, were included. Blood pressure measurement, anthropometric parameters and metabolic markers were measured. Subjects were grouped according the number of CMRFs (Group 1: <2; Group 2: 2; Group 3: 3 or more CMRFs). Using SNPlex, 1251 SNPs potentially associated to clustering of three or more CMRFs were analyzed. Serum metabolomic profile was assessed by 1H NMR spectra using a Brucker Advance DRX 600 spectrometer. From the total population, 1217 (mean age 54±19, 50.6% men) with high genotyping call rate were analysed. A differential metabolomic profile, which included products from mitochondrial metabolism, extra mitochondrial metabolism, branched amino acids and fatty acid signals were observed among the three groups. The comparison of metabolomic patterns between subjects of Groups 1 to 3 for each of the genotypes associated to those subjects with three or more CMRFs revealed two SNPs, the rs174577_AA of FADS2 gene and the rs3803_TT of GATA2 transcription factor gene, with minimal or no statistically significant differences. Subjects with and without three or more CMRFs who shared the same genotype and metabolomic profile differed in the pattern of CMRFS cluster. Subjects of Group 3 and the AA genotype of the rs174577 had a lower prevalence of hypertension compared to the CC and CT genotype. In contrast, subjects of Group 3 and the TT genotype of the rs3803 polymorphism had a lower prevalence of T2DM, although they were predominantly males and had higher values of plasma creatinine. Conclusions The results of the present study add information to the metabolomics profile and to the potential impact of genetic factors on the variants of clustering of cardiometabolic risk factors

  20. Metabolic and inflammatory profiles of biomarkers in obesity, metabolic syndrome, and diabetes in a Mediterranean population. DARIOS Inflammatory study.

    PubMed

    Fernández-Bergés, Daniel; Consuegra-Sánchez, Luciano; Peñafiel, Judith; Cabrera de León, Antonio; Vila, Joan; Félix-Redondo, Francisco Javier; Segura-Fragoso, Antonio; Lapetra, José; Guembe, María Jesús; Vega, Tomás; Fitó, Montse; Elosua, Roberto; Díaz, Oscar; Marrugat, Jaume

    2014-08-01

    There is a paucity of data regarding the differences in the biomarker profiles of patients with obesity, metabolic syndrome, and diabetes mellitus as compared to a healthy, normal weight population. We aimed to study the biomarker profile of the metabolic risk continuum defined by the transition from normal weight to obesity, metabolic syndrome, and diabetes mellitus. We performed a pooled analysis of data from 7 cross-sectional Spanish population-based surveys. An extensive panel comprising 20 biomarkers related to carbohydrate metabolism, lipids, inflammation, coagulation, oxidation, hemodynamics, and myocardial damage was analyzed. We employed age- and sex-adjusted multinomial logistic regression models for the identification of those biomarkers associated with the metabolic risk continuum phenotypes: obesity, metabolic syndrome, and diabetes mellitus. A total of 2851 subjects were included for analyses. The mean age was 57.4 (8.8) years, 1269 were men (44.5%), and 464 participants were obese, 443 had metabolic syndrome, 473 had diabetes mellitus, and 1471 had a normal weight (healthy individuals). High-sensitivity C-reactive protein, apolipoprotein B100, leptin, and insulin were positively associated with at least one of the phenotypes of interest. Apolipoprotein A1 and adiponectin were negatively associated. There are differences between the population with normal weight and that having metabolic syndrome or diabetes with respect to certain biomarkers related to the metabolic, inflammatory, and lipid profiles. The results of this study support the relevance of these mechanisms in the metabolic risk continuum. When metabolic syndrome and diabetes mellitus are compared, these differences are less marked. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  1. Rational medium optimization based on comparative metabolic profiling analysis to improve fumaric acid production.

    PubMed

    Wang, Guanyi; Huang, Di; Qi, Haishan; Wen, Jianping; Jia, Xiaoqiang; Chen, Yunlin

    2013-06-01

    To rationally guide fumaric acid production improvement, metabolic profiling approach was performed to analyze metabolite changes of Rhizopus oryzae FM19 under different fermentation conditions. A correlation between the metabolic profiling and fumaric acid production was revealed by principal component analysis as well as partial least squares. Citric acid, oxaloacetic acid, 2-oxoglutarate, lactic acid, proline, alanine, valine, leucine were identified to be mainly responsible for the metabolism difference, which were involved in the Embden-Meyerhof-Parnas, tricarboxylic acid cycle, amino acid metabolism and fatty acid metabolism. Through the further analysis of metabolites changes together with the above pathways, exogenous addition strategies were developed, which resulted in 14% increase of fumaric acid (up to 56.5 g/L) and less by-products. These results demonstrated that metabolic profiling analysis could be successfully applied to the rational guidance of medium optimization and the productivity improvement of value-added compounds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Effects of valproic acid on organic acid metabolism in children: a metabolic profiling study.

    PubMed

    Price, K E; Pearce, R E; Garg, U C; Heese, B A; Smith, L D; Sullivan, J E; Kennedy, M J; Bale, J F; Ward, R M; Chang, T K H; Abbott, F S; Leeder, J S

    2011-06-01

    Young children are at increased risk for valproic acid (VPA) hepatotoxicity. Urinary organic acid profiles, as a surrogate of mitochondrial function, were obtained in children 1.9 to 17.3 years of age (n = 52) who were undergoing treatment with VPA for seizure disorders. Age-matched patients receiving treatment with carbamazepine (CBZ; n = 50) and healthy children not undergoing treatment (n = 22) served as controls. Age-related changes in organic acid profiles were observed in all three groups. Although the untreated and CBZ control groups were indistinguishable from each other with respect to the principal-component analysis (PCA) score plots of the subjects, a distinct boundary was apparent between the VPA and each of the control groups. Interindividual variability was observed in the VPA-induced alterations in endogenous pathways corresponding to branched-chain amino acid metabolism and oxidative stress. The data suggest that more detailed metabolomic analysis may provide novel insights into biological mechanisms and predictive biomarkers for children at highest risk for serious toxicity.

  3. Metabolic study of enrofloxacin and metabolic profile modifications in broiler chicken tissues after drug administration.

    PubMed

    Morales-Gutiérrez, F J; Barbosa, J; Barrón, D

    2015-04-01

    In this work, the identification and distribution of the metabolites from enrofloxacin (ENR) in liver, kidney and muscle tissues from broiler chickens subjected to a pharmacological treatment was studied. In addition, qualitative analyses of changes in the metabolic profile in those tissues after drug administration were also investigated. As a result, a total of 31 different metabolites from ENR were identified, which ciprofloxacin (CIP) and desethylene-ENR were the major metabolites. After four days of withdrawal period, most of the metabolites were excreted, but residues of ENR and CIP still persisted in tissues at a concentration under the permitted maximum residue limit (MRL). Non-medicated, medicated and post-treatment samples of chicken tissues were clearly clustered according to their metabolite profile by principal component analysis and partial least squares discriminant analysis, which indicates that endogenous metabolites have not returned to their original levels after the withdrawal period. A total of 22 relevant mass features contributing to this separation as potential markers of chicken samples were tentatively identified.

  4. 1H NMR-based profiling reveals differential immune-metabolic networks during influenza virus infection in obese mice.

    PubMed

    Milner, J Justin; Wang, Jue; Sheridan, Patricia A; Ebbels, Tim; Beck, Melinda A; Saric, Jasmina

    2014-01-01

    Obese individuals are at greater risk for death from influenza virus infection. Paralleling human evidence, obese mice are also more susceptible to influenza infection mortality. However, the underlying mechanisms driving greater influenza severity in the obese remain unclear. Metabolic profiling has been utilized in infectious disease models to enhance prognostic or diagnostic methods, and to gain insight into disease pathogenesis by providing a more global picture of dynamic infection responses. Herein, metabolic profiling was used to develop a deeper understanding of the complex processes contributing to impaired influenza protection in obese mice and to facilitate generation of new explanatory hypotheses. Diet-induced obese and lean mice were infected with influenza A/Puerto Rico/8/34. 1H nuclear magnetic resonance-based metabolic profiling of urine, feces, lung, liver, mesenteric white adipose tissue, bronchoalveolar lavage fluid and serum revealed distinct metabolic signatures in infected obese mice, including perturbations in nucleotide, vitamin, ketone body, amino acid, carbohydrate, choline and lipid metabolic pathways. Further, metabolic data was integrated with immune analyses to obtain a more comprehensive understanding of potential immune-metabolic interactions. Of interest, uncovered metabolic signatures in urine and feces allowed for discrimination of infection status in both lean and obese mice at an early influenza time point, which holds prognostic and diagnostic implications for this methodology. These results confirm that obesity causes distinct metabolic perturbations during influenza infection and provide a basis for generation of new hypotheses and use of this methodology in detection of putative biomarkers and metabolic patterns to predict influenza infection outcome.

  5. Development of a Pipeline for Exploratory Metabolic Profiling of Infant Urine.

    PubMed

    Jackson, Frances; Georgakopoulou, Nancy; Kaluarachchi, Manuja; Kyriakides, Michael; Andreas, Nicholas; Przysiezna, Natalia; Hyde, Matthew J; Modi, Neena; Nicholson, Jeremy K; Wijeyesekera, Anisha; Holmes, Elaine

    2016-09-02

    Numerous metabolic profiling pipelines have been developed to characterize the composition of human biofluids and tissues, the vast majority of these being for studies in adults. To accommodate limited sample volume and to take into account the compositional differences between adult and infant biofluids, we developed and optimized sample handling and analytical procedures for studying urine from newborns. A robust pipeline for metabolic profiling using NMR spectroscopy was established, encompassing sample collection, preparation, spectroscopic measurement, and computational analysis. Longitudinal samples were collected from five infants from birth until 14 months of age. Methods of extraction and effects of freezing and sample dilution were assessed, and urinary contaminants from breakdown of polymers in a range of diapers and cotton wool balls were identified and compared, including propylene glycol, acrylic acid, and tert-butanol. Finally, assessment of urinary profiles obtained over the first few weeks of life revealed a dramatic change in composition, with concentrations of phenols, amino acids, and betaine altering systematically over the first few months of life. Therefore, neonatal samples require more stringent standardization of experimental design, sample handling, and analysis compared to that of adult samples to accommodate the variability and limited sample volume.

  6. Evaluation of 1H NMR metabolic profiling using biofluid mixture design.

    PubMed

    Athersuch, Toby J; Malik, Shahid; Weljie, Aalim; Newton, Jack; Keun, Hector C

    2013-07-16

    A strategy for evaluating the performance of quantitative spectral analysis tools in conditions that better approximate background variation in a metabonomics experiment is presented. Three different urine samples were mixed in known proportions according to a {3, 3} simplex lattice experimental design and analyzed in triplicate by 1D (1)H NMR spectroscopy. Fifty-four urinary metabolites were subsequently quantified from the sample spectra using two methods common in metabolic profiling studies: (1) targeted spectral fitting and (2) targeted spectral integration. Multivariate analysis using partial least-squares (PLS) regression showed the latent structure of the spectral set recapitulated the experimental mixture design. The goodness-of-prediction statistic (Q(2)) of each metabolite variable in a PLS model was calculated as a metric for the reliability of measurement, across the sample compositional space. Several metabolites were observed to have low Q(2) values, largely as a consequence of their spectral resonances having low s/n or strong overlap with other sample components. This strategy has the potential to allow evaluation of spectral features obtained from metabolic profiling platforms in the context of the compositional background found in real biological sample sets, which may be subject to considerable variation. We suggest that it be incorporated into metabolic profiling studies to improve the estimation of matrix effects that confound accurate metabolite measurement. This novel method provides a rational basis for exploiting information from several samples in an efficient manner and avoids the use of multiple spike-in authentic standards, which may be difficult to obtain.

  7. Methods of identification employing antibody profiles

    DOEpatents

    Francoeur, Ann-Michele

    1993-12-14

    An identification method, applicable to the identification of animals or inanimate objects, is described. The method takes advantage of the set of individual-specific antibodies that are part of the unique antibody repertoire present in animals, by reacting an effective amount of such antibodies with a particular panel, of n-dimensional array (where n is typically one or two) consisting of an effective amount of many different antigens (typically greater than one thousand), to give antibody-antigen complexes. The profile or pattern formed by the antigen-antibody complexes, termed an antibody fingerprint, when revealed by an effective amount of an appropriate detector molecule, is uniquely representative of a particular individual. The method can similarly be used to distinguish genetically, or otherwise similar individuals, or their body parts containing individual-specific antibodies.

  8. Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments

    PubMed Central

    Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe

    2016-01-01

    Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment. PMID:26883691

  9. Serum Metabolic Profiling Reveals Altered Metabolic Pathways in Patients with Post-traumatic Cognitive Impairments.

    PubMed

    Yi, Lunzhao; Shi, Shuting; Wang, Yang; Huang, Wei; Xia, Zi-an; Xing, Zhihua; Peng, Weijun; Wang, Zhe

    2016-02-17

    Cognitive impairment, the leading cause of traumatic brain injury (TBI)-related disability, adversely affects the quality of life of TBI patients, and exacts a personal and economic cost that is difficult to quantify. The underlying pathophysiological mechanism is currently unknown, and an effective treatment of the disease has not yet been identified. This study aimed to advance our understanding of the mechanism of disease pathogenesis; thus, metabolomics based on gas chromatography/mass spectrometry (GC-MS), coupled with multivariate and univariate statistical methods were used to identify potential biomarkers and the associated metabolic pathways of post-TBI cognitive impairment. A biomarker panel consisting of nine serum metabolites (serine, pyroglutamic acid, phenylalanine, galactose, palmitic acid, arachidonic acid, linoleic acid, citric acid, and 2,3,4-trihydroxybutyrate) was identified to be able to discriminate between TBI patients with cognitive impairment, TBI patients without cognitive impairment and healthy controls. Furthermore, associations between these metabolite markers and the metabolism of amino acids, lipids and carbohydrates were identified. In conclusion, our study is the first to identify several serum metabolite markers and investigate the altered metabolic pathway that is associated with post-TBI cognitive impairment. These markers appear to be suitable for further investigation of the disease mechanisms of post-TBI cognitive impairment.

  10. Probing genetic algorithms for feature selection in comprehensive metabolic profiling approach.

    PubMed

    Zou, Wei; Tolstikov, Vladimir V

    2008-04-01

    Six different clones of 1-year-old loblolly pine (Pinus taeda L.) seedlings grown under standardized conditions in a green house were used for sample preparation and further analysis. Three independent and complementary analytical techniques for metabolic profiling were applied in the present study: hydrophilic interaction chromatography (HILIC-LC/ESI-MS), reversed-phase liquid chromatography (RP-LC/ESI-MS), and gas chromatography all coupled to mass spectrometry (GC/TOF-MS). Unsupervised methods, such as principle component analysis (PCA) and clustering, and supervised methods, such as classification, were used for data mining. Genetic algorithms (GA), a multivariate approach, was probed for selection of the smallest subsets of potentially discriminative classifiers. From more than 2000 peaks found in total, small subsets were selected by GA as highly potential classifiers allowing discrimination among six investigated genotypes. Annotated GC/TOF-MS data allowed the generation of a small subset of identified metabolites. LC/ESI-MS data and small subsets require further annotation. The present study demonstrated that combination of comprehensive metabolic profiling and advanced data mining techniques provides a powerful metabolomic approach for biomarker discovery among small molecules. Utilizing GA for feature selection allowed the generation of small subsets of potent classifiers.

  11. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles

    PubMed Central

    Hauschild, Anne-Christin; Frisch, Tobias; Baumbach, Jörg Ingo; Baumbach, Jan

    2015-01-01

    Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs) in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD). While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD) and bronchial

  12. Carotta: Revealing Hidden Confounder Markers in Metabolic Breath Profiles.

    PubMed

    Hauschild, Anne-Christin; Frisch, Tobias; Baumbach, Jörg Ingo; Baumbach, Jan

    2015-06-10

    Computational breath analysis is a growing research area aiming at identifying volatile organic compounds (VOCs) in human breath to assist medical diagnostics of the next generation. While inexpensive and non-invasive bioanalytical technologies for metabolite detection in exhaled air and bacterial/fungal vapor exist and the first studies on the power of supervised machine learning methods for profiling of the resulting data were conducted, we lack methods to extract hidden data features emerging from confounding factors. Here, we present Carotta, a new cluster analysis framework dedicated to uncovering such hidden substructures by sophisticated unsupervised statistical learning methods. We study the power of transitivity clustering and hierarchical clustering to identify groups of VOCs with similar expression behavior over most patient breath samples and/or groups of patients with a similar VOC intensity pattern. This enables the discovery of dependencies between metabolites. On the one hand, this allows us to eliminate the effect of potential confounding factors hindering disease classification, such as smoking. On the other hand, we may also identify VOCs associated with disease subtypes or concomitant diseases. Carotta is an open source software with an intuitive graphical user interface promoting data handling, analysis and visualization. The back-end is designed to be modular, allowing for easy extensions with plugins in the future, such as new clustering methods and statistics. It does not require much prior knowledge or technical skills to operate. We demonstrate its power and applicability by means of one artificial dataset. We also apply Carotta exemplarily to a real-world example dataset on chronic obstructive pulmonary disease (COPD). While the artificial data are utilized as a proof of concept, we will demonstrate how Carotta finds candidate markers in our real dataset associated with confounders rather than the primary disease (COPD) and bronchial

  13. Effect of probiotics on metabolic profiles in type 2 diabetes mellitus

    PubMed Central

    Li, Caifeng; Li, Xin; Han, Hongqiu; Cui, Hailong; Peng, Min; Wang, Guolin; Wang, Zhiqiang

    2016-01-01

    Abstract Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease which is imposing heavy burden on global health and economy. Recent studies indicate gut microbiota play important role on the pathogenesis and metabolic disturbance of T2DM. As an effective mean of regulating gut microbiota, probiotics are live micro-organisms that are believed to provide a specific health benefit on the host. Whether probiotic supplementation could improve metabolic profiles by modifying gut microbiota in T2DM or not is still in controversy. The aim of the study is to assess the effect of probiotic supplementation on metabolic profiles in T2DM. We searched PubMed, EMBASE, and Cochrane Library up to 12 April 2016. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Data were pooled by using the random-effect model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was assessed and quantified (I2). A total of 12 randomized controlled trials (RCTs) were included. Lipid profiles (n = 508) and fasting blood glucose (FBG) (n = 520) were reported in 9 trials; the homeostasis model of assessment for insulin resistance index (HOMA-IR) (n = 368) and glycosylated hemoglobin (HbA1c) (n = 380) were reported in 6 trials. Probiotics could alleviate FBG (SMD –0.61 mmol/L, 95% CI [–0.92, –0.30], P = 0.0001). Probiotics could increase high-density lipoprotein-cholesterol (HDL-C) (SMD 0.42 mmol/L, 95% CI [0.08, 0.76], P = 0.01). There were no significant differences in low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), HbA1c and HOMA-IR between the treatment group and the control group. Probiotics may improve glycemic control and lipid metabolism in T2DM. Application of probiotic agents might become a new method for glucose management in T2DM. PMID:27368052

  14. Distinct Metabolic Profile of Inhaled Budesonide and Salbutamol in Asthmatic Children during Acute Exacerbation.

    PubMed

    Quan-Jun, Yang; Jian-Ping, Zhang; Jian-Hua, Zhang; Yong-Long, Han; Bo, Xin; Jing-Xian, Zhang; Bona, Dai; Yuan, Zhang; Cheng, Guo

    2017-03-01

    Inhaled budesonide and salbutamol represent the most important and frequently used drugs in asthmatic children during acute exacerbation. However, there is still no consensus about their resulting metabolic derangements; thus, this study was conducted to determine the distinct metabolic profiles of these two drugs. A total of 69 children with asthma during acute exacerbation were included, and their serum and urine were investigated using high-resolution nuclear magnetic resonance (NMR). A metabolomics analysis was performed using a principal component analysis and orthogonal signal correction-partial least squares using SIMCA-P. The different metabolites were identified, and the distinct metabolic profiles were analysed using MetPA. A high-resolution NMR-based serum and urine metabolomics approach was established to study the overall metabolic changes after inhaled budesonide and salbutamol in asthmatic children during acute exacerbation. The perturbed metabolites included 22 different metabolites in the serum and 21 metabolites in the urine. Based on an integrated analysis, the changed metabolites included the following: increased 4-hydroxybutyrate, lactate, cis-aconitate, 5-hydroxyindoleacetate, taurine, trans-4-hydroxy-l-proline, tiglylglycine, 3-hydroxybutyrate, 3-methylhistidine, glucose, cis-aconitate, 2-deoxyinosine and 2-aminoadipate; and decreased alanine, glycerol, arginine, glycylproline, 2-hydroxy-3-methylvalerate, creatine, citrulline, glutamate, asparagine, 2-hydroxyvalerate, citrate, homoserine, histamine, sn-glycero-3-phosphocholine, sarcosine, ornithine, creatinine, glycine, isoleucine and trimethylamine N-oxide. The MetPA analysis revealed seven involved metabolic pathways: arginine and proline metabolism; taurine and hypotaurine metabolism; glycine, serine and threonine metabolism; glyoxylate and dicarboxylate metabolism; methane metabolism; citrate cycle; and pyruvate metabolism. The perturbed metabolic profiles suggest potential metabolic

  15. Feeding fat from distillers dried grains with solubles to dairy heifers: II. Effect on metabolic profile

    USDA-ARS?s Scientific Manuscript database

    The objective of this study was to determine if increased dietary fat from dried distillers grains with solubles (DDGS) in diets of growing heifers affected metabolic profile, plasma fatty acid profile, and reproductive maturation. Thirty-three Holstein heifers (133 ± 18 d old) were used in a 24-wee...

  16. ¹H NMR-based metabolic profiling of human rectal cancer tissue

    PubMed Central

    2013-01-01

    Background Rectal cancer is one of the most prevalent tumor types. Understanding the metabolic profile of rectal cancer is important for developing therapeutic approaches and molecular diagnosis. Methods Here, we report a metabonomics profiling of tissue samples on a large cohort of human rectal cancer subjects (n = 127) and normal controls (n = 43) using 1H nuclear magnetic resonance (1H NMR) based metabonomics assay, which is a highly sensitive and non-destructive method for the biomarker identification in biological systems. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal projection to latent structure with discriminant analysis (OPLS-DA) were applied to analyze the 1H-NMR profiling data to identify the distinguishing metabolites of rectal cancer. Results Excellent separation was obtained and distinguishing metabolites were observed among the different stages of rectal cancer tissues (stage I = 35; stage II = 37; stage III = 37 and stage IV = 18) and normal controls. A total of 38 differential metabolites were identified, 16 of which were closely correlated with the stage of rectal cancer. The up-regulation of 10 metabolites, including lactate, threonine, acetate, glutathione, uracil, succinate, serine, formate, lysine and tyrosine, were detected in the cancer tissues. On the other hand, 6 metabolites, including myo-inositol, taurine, phosphocreatine, creatine, betaine and dimethylglycine were decreased in cancer tissues. These modified metabolites revealed disturbance of energy, amino acids, ketone body and choline metabolism, which may be correlated with the progression of human rectal cancer. Conclusion Our findings firstly identify the distinguishing metabolites in different stages of rectal cancer tissues, indicating possibility of the attribution of metabolites disturbance to the progression of rectal cancer. The altered metabolites may be as potential biomarkers, which would

  17. Metabolic profiling of Lolium perenne shows functional integration of metabolic responses to diverse subtoxic conditions of chemical stress.

    PubMed

    Serra, Anne-Antonella; Couée, Ivan; Renault, David; Gouesbet, Gwenola; Sulmon, Cécile

    2015-04-01

    Plant communities are confronted with a great variety of environmental chemical stresses. Characterization of chemical stress in higher plants has often been focused on single or closely related stressors under acute exposure, or restricted to a selective number of molecular targets. In order to understand plant functioning under chemical stress conditions close to environmental pollution conditions, the C3 grass Lolium perenne was subjected to a panel of different chemical stressors (pesticide, pesticide degradation compound, polycyclic aromatic hydrocarbon, and heavy metal) under conditions of seed-level or root-level subtoxic exposure. Physiological and metabolic profiling analysis on roots and shoots revealed that all of these subtoxic chemical stresses resulted in discrete physiological perturbations and complex metabolic shifts. These metabolic shifts involved stressor-specific effects, indicating multilevel mechanisms of action, such as the effects of glyphosate and its degradation product aminomethylphosphonic acid on quinate levels. They also involved major generic effects that linked all of the subtoxic chemical stresses with major modifications of nitrogen metabolism, especially affecting asparagine, and of photorespiration, especially affecting alanine and glycerate. Stress-related physiological effects and metabolic adjustments were shown to be integrated through a complex network of metabolic correlations converging on Asn, Leu, Ser, and glucose-6-phosphate, which could potentially be modulated by differential dynamics and interconversion of soluble sugars (sucrose, trehalose, fructose, and glucose). Underlying metabolic, regulatory, and signalling mechanisms linking these subtoxic chemical stresses with a generic impact on nitrogen metabolism and photorespiration are discussed in relation to carbohydrate and low-energy sensing.

  18. Metabolic profiling of presymptomatic Huntington’s disease sheep reveals novel biomarkers

    PubMed Central

    Skene, Debra J.; Middleton, Benita; Fraser, Cara K.; Pennings, Jeroen L. A.; Kuchel, Timothy R.; Rudiger, Skye R.; Bawden, C. Simon; Morton, A. Jennifer

    2017-01-01

    The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients. PMID:28223686

  19. Biochemical effects of venlafaxine on astrocytes as revealed by (1)H NMR-based metabolic profiling.

    PubMed

    Sun, Lu; Fang, Liang; Lian, Bin; Xia, Jin-Jun; Zhou, Chan-Juan; Wang, Ling; Mao, Qiang; Wang, Xin-Fa; Gong, Xue; Liang, Zi-Hong; Bai, Shun-Jie; Liao, Li; Wu, Yu; Xie, Peng

    2017-01-31

    As a serotonin-norepinephrine reuptake inhibitor [SNRI], venlafaxine is one of the most commonly prescribed clinical antidepressants, with a broad range of antidepressant effects. Accumulating evidence shows that venlafaxine may target astrocytes to exert its antidepressant activity, although the underlying pharmacological mechanisms remained largely unknown. Here, we used a (1)H nuclear magnetic resonance (NMR)-based metabonomics method coupled with multivariate statistical analysis to characterize the metabolic profiling of astrocytes treated with venlafaxine to explore the potential mechanism of its antidepressant effect. In total, 31 differential metabolites involved in energy, amino acid and lipid metabolism were identified. Ingenuity pathway analysis was used to identify the predicted pathways and biological functions with venlafaxine and fluoxetine. The most significantly altered network was "amino acid metabolism, cellular growth and proliferation", with a score above 20. Certain metabolites (lysine, tyrosine, glutamate, methionine, ethanolamine, fructose-6-phosphate, and phosphorylethanolamine) are involved in and play a central role in this network. Collectively, the biological effects of venlafaxine on astrocytes provide us with the further understanding of the mechanisms by which venlafaxine treats major depressive disorder.

  20. Urine metabolic profiling for the pathogenesis research of erosive oral lichen planus.

    PubMed

    Li, Xu-Zhao; Yang, Xu-Yan; Wang, Yu; Zhang, Shuai-Nan; Zou, Wei; Wang, Yan; Li, Xiao-Nan; Wang, Ling-Shu; Zhang, Zhi-Gang; Xie, Liang-Zhen

    2017-01-01

    Oral lichen planus (OLP) is a relatively common chronic immune-pathological and inflammatory disease and potentially oral precancerous lesion. Erosive OLP patients show the higher rate of malignant transformation than patients with non-erosive OLP. Identifying the potential biomarkers related to erosive OLP may help to understand the pathogenesis of the diseases. Metabolic profiles were compared in control and patient subjects with erosive OLP by using ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods An integrative analysis was used to identify the perturbed metabolic pathways and pathological processes that may be associated with the disease. In total, 12 modulated metabolites were identified and considered as the potential biomarkers of erosive OLP. Multiple metabolic pathways and pathological processes were involved in erosive OLP. The dysregulations of these metabolites could be used to explain the pathogenesis of the disease, which could also be the potential therapeutic targets for the disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. The Association between Obstructive Sleep Apnea and Metabolic Markers and Lipid Profiles

    PubMed Central

    Wu, Wei-Te; Tsai, Su-Shan; Shih, Tung-Sheng; Lin, Ming-Hsiu; Chou, Tzu-Chieh; Ting, Hua; Wu, Trong-Neng; Liou, Saou-Hsing

    2015-01-01

    Purpose The purpose of this study was to investigate the association between apnea-hypopnea index (AHI) and metabolic markers and whether the elevated risk of Metabolic Syndrome (MetS) is related to Obstructive Sleep Apnea (OSA). Methods This cross-sectional study recruited 246 male bus drivers from one transportation company in Taiwan. Each participant was evaluated by a polysomnography (PSG) test and by blood lipids examination. Severity of OSA was categorized according to the apnea-hypopnea index (AHI). Results The results showed that a 73.3% prevalence of MetS in OSA (AHI > 15) and a 80.0% prevalence of MetS in severe OSA (AHI > 30) were found. After adjusting for confounding variables, an increased level of Body-Mass Index (BMI) and two non-MetS cardiovascular risk factors, total cholesterol/HDL-C ratio and TG/HDL-C ratio was significantly associated with AHI in subjects with severe OSA. MetS was about three times to be present in subjects with severe OSA, even adjusted for BMI. Conclusions The findings showed a high prevalence of MetS in OSA among professional drivers, especially in the severe group category. BMI was the major contributing factor to OSA. However, the present study did not find a sensitive clinical marker of a detrimental metabolic profile in OSA patients. PMID:26115005

  2. Profiling of ARDS Pulmonary Edema Fluid Identifies a Metabolically Distinct Subset.

    PubMed

    Rogers, Angela J; Contrepois, Kevin; Wu, Manhong; Zheng, Ming; Peltz, Gary; Ware, Lorraine B; Matthay, Michael A

    2017-03-03

    There is considerable biologic and physiologic heterogeneity among patients who meet standard clinical criteria for acute respiratory distress syndrome (ARDS). In this study, we tested the hypothesis that there exists a sub-group of ARDS patients who exhibit a metabolically distinct profile. We examined undiluted pulmonary edema fluid obtained at the time of endotracheal intubation from 16 clinically phenotyped ARDS patients and 13 control patients with hydrostatic pulmonary edema. Non-targeted metabolic profiling was carried out on the undiluted edema fluid. Univariate and multivariate statistical analyses including principal components analysis (PCA) and partial least squares discriminant analysis (PLSDA) were conducted to find discriminant metabolites. 760 unique metabolites were identified in the pulmonary edema fluid of these 29 patients. We found that a subset of ARDS patients (6/16, 38%) presented a distinct metabolic profile with the overrepresentation of 235 metabolites compared to edema fluid from the other 10 ARDS patients, whose edema fluid metabolic profile was indistinguishable from those of the 13 control patients with hydrostatic edema. This "high metabolite" endotype was characterized by higher concentrations of metabolites belonging to all of the main metabolic classes including lipids, amino acids, and carbohydrates. This distinct group with high metabolite levels in the edema fluid was also associated with a higher mortality rate. Thus, metabolic profiling of the edema fluid of ARDS patients supports the hypothesis that there is considerable biologic heterogeneity among ARDS patients who meet standard clinical and physiologic criteria for ARDS.

  3. Pyrroloquinoline quinone: Metabolism and analytical methods

    SciTech Connect

    Smidt, C.R.

    1990-01-01

    Pyrroloquinoline quinone (PQQ) functions as a cofactor for bacterial oxidoreductases. Whether or not PQQ serves as a cofactor in higher plants and animals remains controversial. Nevertheless, strong evidence exists that PQQ has nutritional importance. In highly purified, chemically defined diets PQQ stimulates animal growth. Further PQQ deprivation impairs connective tissue maturation, particularly when initiated in utero and throughout perinatal development. The study addresses two main objectives: (1) to elucidate basic aspects of the metabolism of PQQ in animals, and (2) to develop and improve existing analytical methods for PQQ. To study intestinal absorption of PQQ, ten mice were administered [[sup 14]C]-PQQ per os. PQQ was readily absorbed (62%) in the lower intestine and was excreted by the kidney within 24 hours. Significant amounts of labeled-PQQ were retained only by skin and kidney. Three approaches were taken to answer the question whether or not PQQ is synthesized by the intestinal microflora of mice. First, dietary antibiotics had no effect on fecal PQQ excretion. Then, no bacterial isolates could be identified that are known to synthesize PQQ. Last, cecal contents were incubated anaerobically with radiolabeled PQQ-precursors with no label appearing in isolated PQQ. Thus, intestinal PQQ synthesis is unlikely. Analysis of PQQ in biological samples is problematic since PQQ forms adducts with nucleophilic compounds and binds to the protein fraction. Existing analytical methods are reviewed and a new approach is introduced that allows for detection of PQQ in animal tissue and foods. PQQ is freed from proteins by ion exchange chromatography, purified on activated silica cartridges, detected by a colorimetric redox-cycling assay, and identified by mass spectrometry. That compounds with the properties of PQQ may be nutritionally important offers interesting areas for future investigation.

  4. Tissue targeted metabonomics: metabolic profiling by microdialysis sampling and microcoil NMR.

    PubMed

    Price, Kristin E; Vandaveer, Shannon S; Lunte, Craig E; Larive, Cynthia K

    2005-08-10

    The concentration of low molecular weight compounds in tissues can yield valuable information about the metabolic state of an organism. Studies of changes in the metabolic state or metabonomics can reflect disease pathways, drug action, or toxicity. This research aims to develop a new approach, tissue targeted metabonomics. Microdialysis sampling and microcoil NMR analysis are employed to compare basal and ischemic metabolic states of various tissues (blood, brain, and heart) of Sprague-Dawley rats. Microdialysis sampling is localized, making the metabolic profile tissue specific. Coupling to NMR analysis is highly advantageous, because a complete metabolic profile is obtained in a single spectrum. However, small sample volumes and low analyte concentrations make analysis of microdialysis samples challenging. Microcoil NMR uses low sample volumes and has improved mass sensitivity, relative to standard 5 mm probes. The coupling of these techniques is a potentially powerful tool for metabonomics analysis.

  5. Identification of a metabolizing enzyme in human kidney by proteomic correlation profiling.

    PubMed

    Sakurai, Hidetaka; Kubota, Kazuishi; Inaba, Shin-Ichi; Takanaka, Kaoru; Shinagawa, Akira

    2013-08-01

    Molecular identification of endogenous enzymes and biologically active substances from complex biological sources remains a challenging task, and although traditional biochemical purification is sometimes regarded as outdated, it remains one of the most powerful methodologies for this purpose. While biochemical purification usually requires large amounts of starting material and many separation steps, we developed an advanced method named "proteomic correlation profiling" in our previous study. In proteomic correlation profiling, we first fractionated biological material by column chromatography, and then calculated each protein's correlation coefficient between the enzyme activity profile and protein abundance profile determined by proteomics technology toward fractions. Thereafter, we could choose possible candidates for the enzyme among proteins with a high correlation value by domain predictions using informatics tools. Ultimately, this streamlined procedure requires fewer purification steps and reduces starting materials dramatically due to low required purity compared with conventional approaches. To demonstrate the generality of this approach, we have now applied an improved workflow of proteomic correlation profiling to a drug metabolizing enzyme and successfully identified alkaline phosphatase, tissue-nonspecific isozyme (ALPL) as a phosphatase of CS-0777 phosphate (CS-0777-P), a selective sphingosine 1-phosphate receptor 1 modulator with potential benefits in the treatment of autoimmune diseases including multiple sclerosis, from human kidney extract. We identified ALPL as a candidate protein only by the 200-fold purification and only from 1 g of human kidney. The identification of ALPL as CS-0777-P phosphatase was strongly supported by a recombinant protein, and contribution of the enzyme in human kidney extract was validated by immunodepletion and a specific inhibitor. This approach can be applied to any kind of enzyme class and biologically active

  6. Targeting misuse of 2-amino-N-ethyl-1-phenylbutane in urine samples: in vitro-in vivo correlation of metabolic profiles and development of LC-TOF-MS method.

    PubMed

    Kobayashi, Masaki; Pelander, Anna; Ketola, Raimo A; Leinonen, Antti; Kuuranne, Tiia

    2015-02-01

    A phenyethylamine derivative, 2-amino-N-ethyl-1-phenylbutane (2-AEPB), has recently been detected in doping control and drugs-of-abuse samples, and identified as a non-labelled ingredient in a dietary supplement. To facilitate efficient control of this substance we have studied the in vitro metabolic behaviour of 2-AEPB with human liver preparation, compared these results with in vivo pathways in human, and finally propose an analytical strategy to target the potential misuse of 2-AEPB for toxicological, forensic and doping control purposes. The major in vitro formed metabolites originated from desethylation (M1) and monohydroxylation (M2). A minor metabolite with hydroxylation/N-oxidation was also observed (M3). In vitro-in vivo correlation was studied in an excretion study with a single, oral dose of 2-AEPB-containing supplement. An unmodified substance was the most abundant target compound and detected until the last point of sample collection (72 h), and the detection of M1 (40 h) and M2 (27 h) demonstrated good correlation to in vitro results. In the study with authentic cases (n = 6), 2-AEPB and M1 were mainly found in free urinary fraction, whereas higher inter-individual variability was observed for M2. It was predominantly conjugated and already within this limited number of cases, the ratio between glucuronide- and sulpho-conjugated fractions varied significantly. As a conclusion, hydrolysis is not mandatory in the routine sample preparation, and as the separation can be based on either gas chromatography or liquid chromatography, this study verifies that routine mass spectrometric detection methods targeted to amphetamine derivatives can be easily extended to control the misuse of 2-AEPB. Copyright © 2014 John Wiley & Sons, Ltd.

  7. Cerebral Metabolic Profiling of Hypothermic Circulatory Arrest with and Without Antegrade Selective Cerebral Perfusion: Evidence from Nontargeted Tissue Metabolomics in a Rabbit Model

    PubMed Central

    Zou, Li-Hua; Liu, Jin-Ping; Zhang, Hao; Wu, Shu-Bin; Ji, Bing-Yang

    2016-01-01

    Background: Antegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA). However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology. Methods: To clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group, n = 6) and without (DHCA [D] group, n = 6) ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student's t-test was applied to test for statistical significance between the two groups. Results: Metabolic profiling of brain was distinctive significantly between the two groups (Q2Y = 0.88 for partial least squares-DA model). In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine (P = 0.0019), 5-methoxyindole-3-acetic acid (P = 0.0499), and 5-hydroxyindole-3-acetic acid (P = 0.0495) in tryptophan metabolism pathways were decreased, and citrulline (P = 0.0158) in urea cycle was increased in group DA comparing to group D. Conclusions: The present study applied metabolomics analysis to identify the cerebral

  8. Meloxicam: metabolic profile and biotransformation products in the rat.

    PubMed

    Schmid, J; Busch, U; Trummlitz, G; Prox, A; Kaschke, S; Wachsmuth, H

    1995-11-01

    1. The metabolic fate of 14C-labelled meloxicam was investigated in the urine and bile of rat following oral and intraduodenal administration. Structural elucidation of metabolites was performed by nuclear magnetic resonance, mass spectrometry (electron impact and fast atom bombardment). 2. A mean total of 76.3% 14C-radioactivity was recovered in urine over 96 h, with the remainder in the faeces. The metabolic pattern in the excreta was independent of dose (1 versus 10 mg/kg) and collection period (0-8 versus 24-48 h). In bile one of the main metabolites was absent. 3. Meloxicam underwent extensive metabolism with only small amounts of unchanged drug recovered in the urine (< 0.5%) or bile (4.5%). Principal routes of biotransformation were: oxidation of the 5-methyl group of the N-heteroaryl-carbamoyl side chain to yield the 5'-hydroxymethyl derivative (33% of metabolites in urine, 22% in bile) and the 5'-carboxy derivative (16% in urine, 49% in bile). Oxidative cleavage of the benzothiazine-ring yielded an oxamic acid metabolite in urine (23.5%), which was not present in bile. 4. The introduction of a methyl-group into the N-heteroaryl-carbamoyl side chain increased lipophilicity and facilitated metabolic excretion compared with structurally related compounds.

  9. Recent Advances in Metabolic Profiling And Imaging of Prostate Cancer

    PubMed Central

    Thapar, Roopa; Titus, Mark A

    2015-01-01

    Cancer is a metabolic disease. Cancer cells, being highly proliferative, show significant alterations in metabolic pathways such as glycolysis, respiration, the tricarboxylic acid (TCA) cycle, oxidative phosphorylation, lipid metabolism, and amino acid metabolism. Metabolites like peptides, nucleotides, products of glycolysis, the TCA cycle, fatty acids, and steroids can be an important read out of disease when characterized in biological samples such as tissues and body fluids like urine, serum, etc. The cancer metabolome has been studied since the 1960s by analytical techniques such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy. Current research is focused on the identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients and distinguish between benign and advanced metastatic forms of the disease. In this review, we discuss the current state of prostate cancer metabolomics, the biomarkers that show promise in distinguishing indolent from aggressive forms of the disease, the strengths and limitations of the analytical techniques being employed, and future applications of metabolomics in diagnostic imaging and personalized medicine of prostate cancer. PMID:25632377

  10. Effects of culture media on metabolic profiling of the human gastric cancer cell line SGC7901.

    PubMed

    Huang, Zicheng; Shao, Wei; Gu, Jinping; Hu, Xiaomin; Shi, Yuanzhi; Xu, Wenqi; Huang, Caihua; Lin, Donghai

    2015-07-01

    Cell culture metabolomics has demonstrated significant advantages in cancer research. However, its applications have been impeded by some influencing factors such as culture media, which could significantly affect cellular metabolic profiles and lead to inaccuracy and unreliability of comparative metabolomic analysis of cells. To evaluate the effects of different culture media on cellular metabolic profiling, we performed NMR-based metabolomic analysis of the human gastric cancer cell line SGC7901 cultured in both RPMI1640 and DMEM. We found that SGC7901 cultured in the two media exhibited distinct metabolic profiles with obviously different levels of discrepant metabolites, even though they showed almost the same cellular morphology and proliferation rates. When SGC7901 originally cultured in RPMI1640 was gradually acclimated in DMEM, both the metabolic profiles and most of the discrepant metabolite levels gradually converged toward those of the cells originally cultured in DMEM without significantly altered cell proliferation rates. However, several metabolite levels did not show the converging trends. Our results indicate that the effects of culture media on metabolic profiling must be carefully taken into account for comparative metabolomic analysis of cell lines. This work may be of benefit to the development of cell culture metabolomics.

  11. Dynamic metabolic profiling of cyanobacterial glycogen biosynthesis under conditions of nitrate depletion

    PubMed Central

    Hasunuma, Tomohisa; Kikuyama, Fumi; Matsuda, Mami; Aikawa, Shimpei; Izumi, Yoshihiro; Kondo, Akihiko

    2013-01-01

    Cyanobacteria represent a globally important biomass because they are responsible for a substantial proportion of primary production in the hydrosphere. Arthrospira platensis is a fast-growing halophilic cyanobacterium capable of accumulating glycogen and has the potential to serve as a feedstock in the fermentative production of third-generation biofuels. Accordingly, enhancing cyanobacterial glycogen production is a promising biofuel production strategy. However, the regulatory mechanism of glycogen metabolism in cyanobacteria is poorly understood. The aim of the present study was to determine the metabolic flux of glycogen biosynthesis using a dynamic metabolomic approach. Time-course profiling of widely targeted cyanobacterial metabolic intermediates demonstrated a global metabolic reprogramming that involves transient increases in the levels of some amino acids during the glycogen production phase induced by nitrate depletion. Also, in vivo labelling with NaH13CO3 enabled direct measurement of metabolic intermediate turnover in A. platensis, revealing that under conditions of nitrate depletion glycogen is biosynthesized with carbon derived from amino acids released from proteins via gluconeogenesis. This dynamic metabolic profiling approach provided conclusive evidence of temporal alterations in the metabolic profile in cyanobacterial cells. PMID:23658429

  12. Dynamic metabolic profiling of cyanobacterial glycogen biosynthesis under conditions of nitrate depletion.

    PubMed

    Hasunuma, Tomohisa; Kikuyama, Fumi; Matsuda, Mami; Aikawa, Shimpei; Izumi, Yoshihiro; Kondo, Akihiko

    2013-07-01

    Cyanobacteria represent a globally important biomass because they are responsible for a substantial proportion of primary production in the hydrosphere. Arthrospira platensis is a fast-growing halophilic cyanobacterium capable of accumulating glycogen and has the potential to serve as a feedstock in the fermentative production of third-generation biofuels. Accordingly, enhancing cyanobacterial glycogen production is a promising biofuel production strategy. However, the regulatory mechanism of glycogen metabolism in cyanobacteria is poorly understood. The aim of the present study was to determine the metabolic flux of glycogen biosynthesis using a dynamic metabolomic approach. Time-course profiling of widely targeted cyanobacterial metabolic intermediates demonstrated a global metabolic reprogramming that involves transient increases in the levels of some amino acids during the glycogen production phase induced by nitrate depletion. Also, in vivo labelling with NaH(13)CO3 enabled direct measurement of metabolic intermediate turnover in A. platensis, revealing that under conditions of nitrate depletion glycogen is biosynthesized with carbon derived from amino acids released from proteins via gluconeogenesis. This dynamic metabolic profiling approach provided conclusive evidence of temporal alterations in the metabolic profile in cyanobacterial cells.

  13. Gene expression profiles of auxin metabolism in maturing apple fruit

    USDA-ARS?s Scientific Manuscript database

    Variation exists among apple genotypes in fruit maturation and ripening patterns that influences at-harvest fruit firmness and postharvest storability. Based on the results from our previous large-scale transcriptome profiling on apple fruit maturation and well-documented auxin-ethylene crosstalk, t...

  14. Metabolic profiles in serum of mouse after chronic exposure to drinking water.

    PubMed

    Zhang, Yan; Wu, Bing; Zhang, Xuxiang; Li, Aimin; Cheng, Shupei

    2011-08-01

    The toxicity of Nanjing drinking water on mouse (Mus musculus) was detected by (1)H nuclear magnetic resonance (NMR)-based metabonomic method. Three groups of mice were fed with drinking water (produced by Nanjing BHK Water Plant), 3.8 μg/L benzo(a)pyrene as contrast, and clean water as control, respectively, for 90 days. It was observed that the levels of lactate, alanine, and creatinine in the mice fed with drinking water were increased and that of valine was decreased. The mice of drinking water group were successfully separated from control. The total concentrations of polycyclic aromatic hydrocarbons (PAHs), phthalates (PAEs), and other organic pollutants in the drinking water were 0.23 μg/L, 4.57 μg/L, and 0.34 μg/L, respectively. In this study, Nanjing drinking water was found to induce distinct perturbations of metabolic profiles on mouse including disorders of glucose-alanine cycle, branched-chain amino acid and energy metabolism, and dysfunction of kidney. This study suggests that metabonomic method is feasible and sensitive to evaluate potential toxic effects of drinking water.

  15. Metabolic profiling identification of metabolites formed in Mediterranean mussels (Mytilus galloprovincialis) after diclofenac exposure.

    PubMed

    Bonnefille, Bénilde; Arpin-Pont, Lauren; Gomez, Elena; Fenet, Hélène; Courant, Frédérique

    2017-04-01

    Despite the growing concern on the presence of pharmaceutically active compounds in the environment, few studies have been conducted on their metabolism in marine organisms. In this study, a non-targeted strategy based on the generation of chemical profiles generated by liquid chromatography combined with high resolution mass spectrometry was used to highlight metabolite production by the Mediterranean mussel (Mytilus galloprovincialis) after diclofenac exposure. This method allowed revealing the production of 13 metabolites in mussel tissues. Three of them were phase I metabolites, including 4'-hydroxy-diclofenac and 5-hydroxy-diclofenac. The remaining 10 were phase II metabolites, including sulfate and amino acids conjugates. Among all of the metabolites highlighted, 5 were reported for the first time in an aquatic organism exposed to diclofenac.

  16. Associations between Ionomic Profile and Metabolic Abnormalities in Human Population

    PubMed Central

    An, Peng; Yu, Danxia; Yu, Zhijie; Li, Huaixing; Sheng, Hongguang; Cai, Lu; Xue, Jun; Jing, Miao; Li, Yixue; Lin, Xu; Wang, Fudi

    2012-01-01

    Background Few studies assessed effects of individual and multiple ions simultaneously on metabolic outcomes, due to methodological limitation. Methodology/Principal Findings By combining advanced ionomics and mutual information, a quantifying measurement for mutual dependence between two random variables, we investigated associations of ion modules/networks with overweight/obesity, metabolic syndrome (MetS) and type 2 diabetes (T2DM) in 976 middle-aged Chinese men and women. Fasting plasma ions were measured by inductively coupled plasma mass spectroscopy. Significant ion modules were selected by mutual information to construct disease related ion networks. Plasma copper and phosphorus always ranked the first two among three specific ion networks associated with overweight/obesity, MetS and T2DM. Comparing the ranking of ion individually and in networks, three patterns were observed (1) “Individual ion,” such as potassium and chrome, which tends to work alone; (2) “Module ion,” such as iron in T2DM, which tends to act in modules/network; and (3) “Module-individual ion,” such as copper in overweight/obesity, which seems to work equivalently in either way. Conclusions In conclusion, by using the novel approach of the ionomics strategy and the information theory, we observed potential associations of ions individually or as modules/networks with metabolic disorders. Certainly, these findings need to be confirmed in future biological studies. PMID:22719963

  17. Gestational dating by metabolic profile at birth: a California cohort study.

    PubMed

    Jelliffe-Pawlowski, Laura L; Norton, Mary E; Baer, Rebecca J; Santos, Nicole; Rutherford, George W

    2016-04-01

    Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (<37 weeks) from term births and to assign a specific gestational age in the PTB group. We evaluated a cohort of 729,503 singleton newborns with a California birth in 2005 through 2011 who had routine newborn metabolic screening and fetal ultrasound dating at 11-20 weeks' gestation. Using training and testing subsets (divided in a ratio of 3:1) we evaluated the association among PTB, target newborn characteristics, acylcarnitines, amino acids, thyroid-stimulating hormone, 17-hydroxyprogesterone, and galactose-1-phosphate-uridyl-transferase. We used multivariate backward stepwise regression to test for associations and linear discriminate analyses to create a linear function for PTB and to assign a specific week of gestation. We used sensitivity, specificity, and positive predictive value to evaluate the performance of linear functions. Along with birthweight and infant age at test, we included 35 of the 51 metabolic markers measured in the final multivariate model comparing PTBs and term births. Using a linear discriminate

  18. Gestational dating by metabolic profile at birth: a California cohort study

    PubMed Central

    Jelliffe-Pawlowski, Laura L.; Norton, Mary E.; Baer, Rebecca J.; Santos, Nicole; Rutherford, George W.

    2016-01-01

    Background Accurate gestational dating is a critical component of obstetric and newborn care. In the absence of early ultrasound, many clinicians rely on less accurate measures, such as last menstrual period or symphysis-fundal height during pregnancy, or Dubowitz scoring or the Ballard (or New Ballard) method at birth. These measures often underestimate or overestimate gestational age and can lead to misclassification of babies as born preterm, which has both short- and long-term clinical care and public health implications. Objective We sought to evaluate whether metabolic markers in newborns measured as part of routine screening for treatable inborn errors of metabolism can be used to develop a population-level metabolic gestational dating algorithm that is robust despite intrauterine growth restriction and can be used when fetal ultrasound dating is not available. We focused specifically on the ability of these markers to differentiate preterm births (PTBs) (<37 weeks) from term births and to assign a specific gestational age in the PTB group. Study Design We evaluated a cohort of 729,503 singleton newborns with a California birth in 2005 through 2011 who had routine newborn metabolic screening and fetal ultrasound dating at 11–20 weeks’ gestation. Using training and testing subsets (divided in a ratio of 3:1) we evaluated the association among PTB, target newborn characteristics, acylcarnitines, amino acids, thyroid-stimulating hormone, 17-hydroxyprogesterone, and galactose-1-phosphate-uridyl-transferase. We used multivariate backward stepwise regression to test for associations and linear discriminate analyses to create a linear function for PTB and to assign a specific week of gestation. We used sensitivity, specificity, and positive predictive value to evaluate the performance of linear functions. Results Along with birthweight and infant age at test, we included 35 of the 51 metabolic markers measured in the final multivariate model comparing PTBs and

  19. The metabolome profiling and pathway analysis in metabolic healthy and abnormal obesity.

    PubMed

    Chen, H-H; Tseng, Y J; Wang, S-Y; Tsai, Y-S; Chang, C-S; Kuo, T-C; Yao, W-J; Shieh, C-C; Wu, C-H; Kuo, P-H

    2015-08-01

    Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity. We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways. A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation. Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.

  20. Role of Ketotifen on metabolic profiles, inflammation and oxidative stress in diabetic rats.

    PubMed

    Chen, Zimiao; Sun, Hongwei; Wang, Jian; Ni, Liansong; Gu, Xuejiang; Ge, Shengjie; Chen, Qiong; Mu, Liangshan; Cheng, Xingbo

    2017-03-17

    We aim to explore effects of Ketotifen on metabolic profiles, inflammation and oxidative stress. Sprague Dawley (SD) male rats were randomly divided into normal control group (NC) and experimental groups, and experimental group rats were fed with high-sugar and fat diet for 6 weeks. Then, experimental group rats were divided into diabetes group (DM) and ketotifen treatment group (KT). KT group was given ketotifen via Intragastric for 8 weeks with the dosage of 0.09 mg/kg•d. Fasting plasma glucose (FPG) was measured using glucose oxidase-phenol amino phenazone method. Fasting insulin (FINS), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were tested by enzyme-linked immunosorbent assay. Malondialdehyde (MDA) and superoxide dismutase (SOD) were quantified by spectrophotometer method. Before Ketotifen administration, compared with NC group, DM and KT groups showed significantly high levels of body weight, FPG, FINS, HOMA-IR, TC, TG, LDL, IL-6, TNF-α and MDA, and lower levels of HDL and SOD (All p <0.05). After 4 weeks of Ketotifen administration, levels of body weight, FPG, FINS, HOMA-IR, TC, TG, LDL, IL-6, TNF-α in KT group decreased significantly, and levels of HDL and SOD elevated significantly (All p <0.05). After 8 weeks of Ketotifen administration, levels of body weight, FPG, FINS, HOMA-IR, TC, TG, LDL, IL-6, TNF-α and MDA in KT group decreased more obviously, and levels of HDL and SOD elevated significantly further (All p <0.05). Ketotifen improved metabolic profiles, and ameliorated status of inflammation and oxidative stress.

  1. Evaluation of sampling and extraction methodologies for the global metabolic profiling of Saccharophagus degradans.

    PubMed

    Shin, Min Hye; Lee, Do Yup; Liu, Kwang-Hyeon; Fiehn, Oliver; Kim, Kyoung Heon

    2010-08-01

    Metabolomics is based on the unbiased and global analysis of metabolites of organisms at specific time points. Therefore, the nonselective and reproducible recovery of all existing metabolites while preventing their transformation is the ideal criterion for metabolome sample preparation. We evaluated currently used sampling methods and extraction solvents for global metabolic profiling of a gram-negative bacterium, Saccharophagus degradans, using gas chromatography-time-of-flight mass spectrometry (GC-TOF MS) with an emphasis on three steps: the sampling method, which consisted of cold methanol quenching or fast filtration; the subsequent washing step; and the extraction solvents. After cold methanol quenching with 70% (v/v) methanol at -70 degrees C, washing with 2.3% NaCl produced a serious loss of intracellular metabolites. In addition, when cold methanol quenching and fast filtration were compared, severe cell leakage caused by cold methanol quenching resulted in a significant loss of intracellular metabolites, which was confirmed by spectrometric analysis at 260 and 280 nm. Upon evaluation of extraction solvents such as pure methanol (MeOH), acetonitrile/water (50ACN; 1:1, v/v), acetonitrile/methanol/water mixture (AMW; 2:2:1), and water/isopropanol/methanol (WiPM; 2:2:5). AMW and WiPM were found to be superior extraction solvents for S. degradans based on the total peak intensities of the metabolites, the total number of metabolite peaks, and the reproducibility of recovered metabolite quantities; however, the metabolite profiles differed significantly between AMW and WiPM. This is the first evaluation of each step of sample preparation involved in global scale metabolic analysis by GC-TOF MS, which can be used as a model in the preparation of organism-specific samples for metabolome analysis.

  2. Altered Circadian Rhythm and Metabolic Gene Profile in Rats Subjected to Advanced Light Phase Shifts

    PubMed Central

    Herrero, Laura; Valcarcel, Lorea; da Silva, Crhistiane Andressa; Albert, Nerea; Diez-Noguera, Antoni; Cambras, Trinitat; Serra, Dolors

    2015-01-01

    The circadian clock regulates metabolic homeostasis and its disruption predisposes to obesity and other metabolic diseases. However, the effect of phase shifts on metabolism is not completely understood. We examined whether alterations in the circadian rhythm caused by phase shifts induce metabolic changes in crucial genes that would predispose to obesity. Three-month-old rats were maintained on a standard diet under lighting conditions with chronic phase shifts consisting of advances, delays or advances plus delays. Serum leptin, insulin and glucose levels decreased only in rats subjected to advances. The expression of the clock gene Bmal 1 increased in the hypothalamus, white adipose tissue (WAT), brown adipose tissue (BAT) and liver of the advanced group compared to control rats. The advanced group showed an increase in hypothalamic AgRP and NPY mRNA, and their lipid metabolism gene profile was altered in liver, WAT and BAT. WAT showed an increase in inflammation and ER stress and brown adipocytes suffered a brown-to-white transformation and decreased UCP-1 expression. Our results indicate that chronic phase advances lead to significant changes in neuropeptides, lipid metabolism, inflammation and ER stress gene profile in metabolically relevant tissues such as the hypothalamus, liver, WAT and BAT. This highlights a link between alteration of the circadian rhythm and metabolism at the transcriptional level. PMID:25837425

  3. Association between urinary metabolic profile and the intestinal effects of cocoa in rats.

    PubMed

    Massot-Cladera, Malen; Mayneris-Perxachs, Jordi; Costabile, Adele; Swann, Jonathan R; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

    2017-03-01

    The aim of this study was to elucidate the relationship between the urinary metabolic fingerprint and the effects of cocoa and cocoa fibre on body weight, hormone metabolism, intestinal immunity and microbiota composition. To this effect, Wistar rats were fed, for 3 weeks, a diet containing 10 % cocoa (C10) or two other diets with same the proportion of fibres: one based on cocoa fibre (CF) and another containing inulin as a reference (REF) diet. The rats' 24 h urine samples were analysed by an untargeted 1H NMR spectroscopy-based metabonomic approach. Concentrations of faecal IgA and plasma metabolic hormones were also quantified. The C10 diet decreased the intestinal IgA, plasma glucagon-like peptide-1 and glucagon concentrations and increased ghrelin levels compared with those in the REF group. Clear differences were observed between the metabolic profiles from the C10 group and those from the CF group. Urine metabolites derived from cocoa correlated with the cocoa effects on body weight, immunity and the gut microbiota. Overall, cocoa intake alters the host and bacterial metabolism concerning energy and amino acid pathways, leading to a metabolic signature that can be used as a marker for consumption. This metabolic profile correlates with body weight, metabolic hormones, intestinal immunity and microbiota composition.

  4. Prediction of future risk of insulin resistance and metabolic syndrome based on Korean boy's metabolite profiling.

    PubMed

    Lee, AeJin; Jang, Han Byul; Ra, Moonjin; Choi, Youngshim; Lee, Hye-Ja; Park, Ju Yeon; Kang, Jae Heon; Park, Kyung-Hee; Park, Sang Ick; Song, Jihyun

    2015-01-01

    Childhood obesity is strongly related to future insulin resistance and metabolic syndrome. Thus, identifying early biomarkers of obesity-related diseases based on metabolic profiling is useful to control future metabolic disorders. We compared metabolic profiles between obese and normal-weight children and investigated specific biomarkers of future insulin resistance and metabolic syndrome. In all, 186 plasma metabolites were analysed at baseline and after 2 years in 109 Korean boys (age 10.5±0.4 years) from the Korean Child Obesity Cohort Study using the AbsoluteIDQ™ p180 Kit. We observed that levels of 41 metabolites at baseline and 40 metabolites at follow-up were significantly altered in obese children (p<0.05). Obese children showed significantly higher levels of branched-chain amino acids (BCAAs) and several acylcarnitines and lower levels of acyl-alkyl phosphatidylcholines. Also, baseline BCAAs were significantly positively correlated with both homeostasis model assessment for insulin resistance (HOMA-IR) and continuous metabolic risk score at the 2-year follow-up. In logistic regression analyses with adjustments for degree of obesity at baseline, baseline BCAA concentration, greater than the median value, was identified as a predictor of future risk of insulin resistance and metabolic syndrome. High BCAA concentration could be "early" biomarkers for predicting future metabolic diseases. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  5. High-Throughput Metabolic Profiling of Soybean Leaves by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry.

    PubMed

    Yilmaz, Ali; Rudolph, Heather L; Hurst, Jerod J; Wood, Troy D

    2016-01-19

    As a relatively recent research field, plant metabolomics has gained increasing interest in the past few years and has been applied to answer biological questions through large-scale qualitative and quantitative analyses of the plant metabolome. The combination of sensitivity and selectivity offered by mass spectrometry (MS) for measurement of many metabolites in a single shot makes it an indispensable platform in metabolomics. In this regard, Fourier-transform ion cyclotron resonance (FTICR) has the unique advantage of delivering high mass resolving power and mass accuracy simultaneously, making it ideal for the study of complex mixtures such as plant extracts. Here we optimize soybean leaf extraction methods compatible with high-throughput reproducible MS-based metabolomics. In addition, matrix-assisted laser desorption ionization (MALDI) and direct LDI of soybean leaves are compared for metabolite profiling. The extraction method combined with electrospray (ESI)-FTICR is supported by the significant reduction of chlorophyll and its related metabolites as the growing season moves from midsummer to the autumn harvest day. To our knowledge for the first time, the use of ESI-FTICR MS and MALDI-FTICR MS is described in a complementary manner with the aim of metabolic profiling of plant leaves that have been collected at different time points during the growing season.

  6. Metabolic Profiling and Antioxidant Assay of Metabolites from Three Radish Cultivars (Raphanus sativus).

    PubMed

    Park, Chang Ha; Baskar, Thanislas Bastin; Park, Soo-Yun; Kim, Sun-Ju; Valan Arasu, Mariadhas; Al-Dhabi, Naif Abdullah; Kim, Jae Kwang; Park, Sang Un

    2016-01-28

    A total of 13 anthocyanins and 33 metabolites; including organic acids, phenolic acids, amino acids, organic compounds, sugar acids, sugar alcohols, and sugars, were profiled in three radish cultivars by using high-performance liquid chromatography (HPLC) and gas chromatography time-of-flight mass spectrometry (GC-TOFMS)-based metabolite profiling. Total phenolics and flavonoids and their in vitro antioxidant activities were assessed. Pelargonidins were found to be the major anthocyanin in the cultivars studied. The cultivar Man Tang Hong showed the highest level of anthocyanins (1.89 ± 0.07 mg/g), phenolics (0.0664 ± 0.0033 mg/g) and flavonoids (0.0096 ± 0.0004 mg/g). Here; the variation of secondary metabolites in the radishes is described, as well as their association with primary metabolites. The low-molecular-weight hydrophilic metabolite profiles were subjected to principal component analysis (PCA), hierarchical clustering analysis (HCA), Pearson's correlation analysis. PCA fully distinguished the three radish cultivars tested. The polar metabolites were strongly correlated between metabolites that participate in the TCA cycle. The chemometrics results revealed that TCA cycle intermediates and free phenolic acids as well as anthocyanins were higher in the cultivar Man Tang Hong than in the others. Furthermore; superoxide radical scavenging activities and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging were investigated to elucidate the antioxidant activity of secondary metabolites in the cultivars. Man Tang Hong showed the highest superoxide radical scavenging activity (68.87%) at 1000 μg/mL, and DPPH activity (20.78%), followed by Seo Ho and then Hong Feng No. 1. The results demonstrate that GC-TOFMS-based metabolite profiling, integrated with chemometrics, is an applicable method for distinguishing phenotypic variation and determining biochemical reactions connecting primary and secondary metabolism. Therefore; this study might provide

  7. Changes in metabolic profiles after the Great East Japan Earthquake: a retrospective observational study

    PubMed Central

    2013-01-01

    Background A magnitude 9.0 earthquake struck off eastern Japan in March 2011. Many survivors have been living in temporary houses provided by the local government since they lost their houses as a result of the great tsunami (tsunami group) or the expected high-dose radiation resulting from the nuclear accident at the Fukushima Daiichi Nuclear Power Plant (radiation group). The tsunami was more than 9 m high in Soma, Fukushima, which is located 30 km north of the Fukushima Daiichi Nuclear Power Plant and adjacent to the mandatory evacuation area. A health screening program was held for the evacuees in Soma in September 2011. The aim of this study was to compare the metabolic profiles of the evacuees before and after the disaster. We hypothesized that the evacuees would experience deteriorated metabolic status based on previous reports of natural disasters. Methods Data on 200 subjects who attended a health screening program in September or October of 2010 (pre-quake) and 2011 (post-quake) were retrospectively reviewed and included in this study. Pre-quake and post-quake results of physical examinations and laboratory tests were compared in the tsunami and radiation groups. A multivariate regression model was used to determine pre-quake predictive factors for elevation of hemoglobin A1c (HbA1c) in the tsunami group. Results Significantly higher values of body weight, body mass index, waist circumference, and HbA1c and lower high-density lipoprotein cholesterol levels were found at the post-quake screening when compared with the pre-quake levels (p = 0.004, p = 0.03, p = 0.008, p < 0.001, and p = 0.03, respectively). A significantly higher proportion of subjects in the tsunami group with high HbA1c, defined as ≥5.7%, was observed after the quake (34.3%) than before the quake (14.8%) (p < 0.001). Regional factors, periodic clinic visits, and waist circumference before the quake were identified as predictive factors on multivariate analysis for the deterioration

  8. Metalaxyl: persistence, degradation, metabolism, and analytical methods.

    PubMed

    Sukul, P; Spiteller, M

    2000-01-01

    Metalaxyl is a systemic fungicide used to control plant diseases caused by Oomycete fungi. Its formulations include granules, wettable powders, dusts, and emulsifiable concentrates. Application may be by foliar or soil incorporation, surface spraying (broadcast or band), drenching, and seed treatment. Metalaxyl registered products either contain metalaxyl as the sole active ingredient or are combined with other active ingredients (e.g., captan, mancozeb, copper compounds, carboxin). Due to its broad-spectrum activity, metalaxyl is used world-wide on a variety of fruit and vegetable crops. Its effectiveness results from inhibition of uridine incorporation into RNA and specific inhibition of RNA polymerase-1. Metalaxyl has both curative and systemic properties. Its mammalian toxicity is classified as EPA toxicity class III and it is also relatively non-toxic to most nontarget arthropod and vertebrate species. Adequate analytical methods of TLC, GLC, HPLC, MS, and other techniques are available for identification and determination of metalaxyl residues and its metabolites. Available laboratory and field studies indicate that metalaxyl is stable to hydrolysis under normal environmental pH values, It is also photolytically stable in water and soil when exposed to natural sunlight. Its tolerance to a wide range of pH, light, and temperature leads to its continued use in agriculture. Metalaxyl is photodecomposed in UV light, and photoproducts are formed by rearrangement of the N-acyl group to the aromatic ring, demethoxylation, N-deacylation, and elimination of the methoxycarbonyl group from the molecule. Photosensitizers such as humic acid, TiO2, H2O2, acetone, and riboflavin accelerate its photodecomposition. Information is provided on the fate of metalaxyl in plant, soil, water, and animals. Major metabolic routes include hydrolysis of the methyl ester and methyl ether oxidation of the ring-methyl groups. The latter are precursors of conjugates in plants and animals

  9. Arsenic Exposure Perturbs the Gut Microbiome and Its Metabolic Profile in Mice: An Integrated Metagenomics and Metabolomics Analysis

    PubMed Central

    Abo, Ryan Phillip; Schlieper, Katherine Ann; Graffam, Michelle E.; Levine, Stuart; Wishnok, John S.; Swenberg, James A.; Tannenbaum, Steven R.; Fox, James G.

    2014-01-01

    Background: The human intestine is host to an enormously complex, diverse, and vast microbial community—the gut microbiota. The gut microbiome plays a profound role in metabolic processing, energy production, immune and cognitive development, epithelial homeostasis, and so forth. However, the composition and diversity of the gut microbiome can be readily affected by external factors, which raises the possibility that exposure to toxic environmental chemicals leads to gut microbiome alteration, or dysbiosis. Arsenic exposure affects large human populations worldwide and has been linked to a number of diseases, including cancer, diabetes, and cardiovascular disorders. Objectives: We investigated the impact of arsenic exposure on the gut microbiome composition and its metabolic profiles. Methods: We used an integrated approach combining 16S rRNA gene sequencing and mass spectrometry–based metabolomics profiling to examine the functional impact of arsenic exposure on the gut microbiome. Results: 16S rRNA gene sequencing revealed that arsenic significantly perturbed the gut microbiome composition in C57BL/6 mice after exposure to 10 ppm arsenic for 4 weeks in drinking water. Moreover, metabolomics profiling revealed a concurrent effect, with a number of gut microflora–related metabolites being perturbed in multiple biological matrices. Conclusions: Arsenic exposure not only alters the gut microbiome community at the abundance level but also substantially disturbs its metabolic profiles at the function level. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism by which arsenic exposure leads to or exacerbates human diseases. Citation: Lu K, Abo RP, Schlieper KA, Graffam ME, Levine S, Wishnok JS, Swenberg JA, Tannenbaum SR, Fox JG. 2014. Arsenic exposure perturbs the gut microbiome and its metabolic profile in mice: an integrated metagenomics and metabolomics analysis. Environ Health

  10. From Metabolomics to Fluxomics: A Computational Procedure to Translate Metabolite Profiles into Metabolic Fluxes

    PubMed Central

    Cortassa, Sonia; Caceres, Viviane; Bell, Lauren N.; O’Rourke, Brian; Paolocci, Nazareno; Aon, Miguel A.

    2015-01-01

    We describe a believed-novel procedure for translating metabolite profiles (metabolome) into the set of metabolic fluxes (fluxome) from which they originated. Methodologically, computational modeling is integrated with an analytical platform comprising linear optimization, continuation and dynamic analyses, and metabolic control. The procedure was tested with metabolite profiles obtained from ex vivo mice Langendorff-heart preparations perfused with glucose. The metabolic profiles were analyzed using a detailed kinetic model of the glucose catabolic pathways including glycolysis, pentose phosphate (PP), glycogenolysis, and polyols to translate the glucose metabolome of the heart into the fluxome. After optimization, the ability of the model to simulate the initial metabolite profile was confirmed, and metabolic fluxes as well as the structure of control and regulation of the glucose catabolic network could be calculated. We show that the step catalyzed by phosphofructokinase together with ATP demand and glycogenolysis exert the highest control on the glycolytic flux. The negative flux control exerted by phosphofructokinase on the PP and polyol pathways revealed that the extent of glycolytic flux directly affects flux redirection through these pathways, i.e., the higher the glycolytic flux the lower the PP and polyols. This believed-novel methodological approach represents a step forward that may help in designing therapeutic strategies targeted to diagnose, prevent, and treat metabolic diseases. PMID:25564863

  11. Metabolic profiling of Burkholderia cenocepacia, Burkholderia ambifaria, and Burkholderia pyrrocinia isolates from maize rhizosphere.

    PubMed

    Alisi, Chiara; Lasinio, Giovanna Jona; Dalmastri, Claudia; Sprocati, AnnaRosa; Tabacchioni, Silvia; Bevivino, Annamaria; Chiarini, Luigi

    2005-10-01

    Burkholderia cenocepacia, Burkholderia ambifaria, and Burkholderia pyrrocinia are the Burkholderia cepacia complex (Bcc) species most frequently associated with roots of crop plants. To investigate the ecophysiological diversity of these species, metabolic profiling of maize rhizosphere isolates was carried out by means of the Biolog system, using GN2 and SFN2 plates and different parameters related to optical density (OD). The metabolic profiles produced by the SFN2 and GN2 plates were identical, but the SFN2's narrower range of OD values and significantly longer reaction times made these plates less suitable for differentiation of isolates. Principal component analysis of maximum OD (ODM) and maximum substrate oxidation rate (muM) data generated by GN2 plates allowed the selection of a reduced number of carbon sources. Statistical analysis of ODM values highlighted marked differences between the metabolic profiles of B. cenocepacia and B. ambifaria, whereas metabolic profiles of B. pyrrocinia clustered very often with those of B. cenocepacia. Analysis of the mu(M) parameter resulted in a slightly lower differentiation among the three Bcc species and a higher metabolic diversity within the single species, in particular within B. cenocepacia. Finally, B. cenocepacia and B. pyrrocinia showed generally higher oxidation rates than B. ambifaria on those GN2 substrates that commonly occur in maize root exudates.

  12. Metabolic profiling of Lolium perenne shows functional integration of metabolic responses to diverse subtoxic conditions of chemical stress

    PubMed Central

    Serra, Anne-Antonella; Couée, Ivan; Renault, David; Gouesbet, Gwenola; Sulmon, Cécile

    2015-01-01

    Plant communities are confronted with a great variety of environmental chemical stresses. Characterization of chemical stress in higher plants has often been focused on single or closely related stressors under acute exposure, or restricted to a selective number of molecular targets. In order to understand plant functioning under chemical stress conditions close to environmental pollution conditions, the C3 grass Lolium perenne was subjected to a panel of different chemical stressors (pesticide, pesticide degradation compound, polycyclic aromatic hydrocarbon, and heavy metal) under conditions of seed-level or root-level subtoxic exposure. Physiological and metabolic profiling analysis on roots and shoots revealed that all of these subtoxic chemical stresses resulted in discrete physiological perturbations and complex metabolic shifts. These metabolic shifts involved stressor-specific effects, indicating multilevel mechanisms of action, such as the effects of glyphosate and its degradation product aminomethylphosphonic acid on quinate levels. They also involved major generic effects that linked all of the subtoxic chemical stresses with major modifications of nitrogen metabolism, especially affecting asparagine, and of photorespiration, especially affecting alanine and glycerate. Stress-related physiological effects and metabolic adjustments were shown to be integrated through a complex network of metabolic correlations converging on Asn, Leu, Ser, and glucose-6-phosphate, which could potentially be modulated by differential dynamics and interconversion of soluble sugars (sucrose, trehalose, fructose, and glucose). Underlying metabolic, regulatory, and signalling mechanisms linking these subtoxic chemical stresses with a generic impact on nitrogen metabolism and photorespiration are discussed in relation to carbohydrate and low-energy sensing. PMID:25618145

  13. Mathematical methods to analysis of topology, functional variability and evolution of metabolic systems based on different decomposition concepts.

    PubMed

    Mrabet, Yassine; Semmar, Nabil

    2010-05-01

    Complexity of metabolic systems can be undertaken at different scales (metabolites, metabolic pathways, metabolic network map, biological population) and under different aspects (structural, functional, evolutive). To analyse such a complexity, metabolic systems need to be decomposed into different components according to different concepts. Four concepts are presented here consisting in considering metabolic systems as sets of metabolites, chemical reactions, metabolic pathways or successive processes. From a metabolomic dataset, such decompositions are performed using different mathematical methods including correlation, stiochiometric, ordination, classification, combinatorial and kinetic analyses. Correlation analysis detects and quantifies affinities/oppositions between metabolites. Stoichiometric analysis aims to identify the organisation of a metabolic network into different metabolic pathways on the hand, and to quantify/optimize the metabolic flux distribution through the different chemical reactions of the system. Ordination and classification analyses help to identify different metabolic trends and their associated metabolites in order to highlight chemical polymorphism representing different variability poles of the metabolic system. Then, metabolic processes/correlations responsible for such a polymorphism can be extracted in silico by combining metabolic profiles representative of different metabolic trends according to a weighting bootstrap approach. Finally evolution of metabolic processes in time can be analysed by different kinetic/dynamic modelling approaches.

  14. Biochemical Association of Metabolic Profile and Microbiome in Chronic Pressure Ulcer Wounds

    PubMed Central

    Ammons, Mary Cloud B.; Morrissey, Kathryn; Tripet, Brian P.; Van Leuven, James T.; Han, Anne; Lazarus, Gerald S.; Zenilman, Jonathan M.; Stewart, Philip S.; James, Garth A.; Copié, Valérie

    2015-01-01

    Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment. PMID:25978400

  15. Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.

    PubMed

    Ammons, Mary Cloud B; Morrissey, Kathryn; Tripet, Brian P; Van Leuven, James T; Han, Anne; Lazarus, Gerald S; Zenilman, Jonathan M; Stewart, Philip S; James, Garth A; Copié, Valérie

    2015-01-01

    Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.

  16. Radiation Changes the Metabolic Profiling of Melanoma Cell Line B16

    PubMed Central

    Yu, Yating; Liang, Wei; Zheng, Qinghui; Huang, Xianing; Huang, Yong; Lu, Xiaoling; Zhao, Yongxiang

    2016-01-01

    Radiation therapy can be an effective way to kill cancer cells using ionizing radiation, but some tumors are resistant to radiation therapy and the underlying mechanism still remains elusive. It is therefore necessary to establish an appropriate working model to study and monitor radiation-mediated cancer therapy. In response to cellular stress, the metabolome is the integrated profiling of changes in all metabolites in cells, which can be used to investigate radiation tolerance mechanisms and identify targets for cancer radiation sensibilization. In this study, using 1H nuclear magnetic resonance for untargeted metabolic profiling in radiation-tolerant mouse melanoma cell line B16, we comprehensively investigated changes in metabolites and metabolic network in B16 cells in response to radiation. Principal component analysis and partial least squares discriminant analysis indicated the difference in cellular metabolites between the untreated cells and X-ray radiated cells. In radiated cells, the content of alanine, glutamate, glycine and choline was increased, while the content of leucine, lactate, creatine and creatine phosphate was decreased. Enrichment analysis of metabolic pathway showed that the changes in metabolites were related to multiple metabolic pathways including the metabolism of glycine, arginine, taurine, glycolysis, and gluconeogenesis. Taken together, with cellular metabolome study followed by bioinformatic analysis to profile specific metabolic pathways in response to radiation, we deepened our understanding of radiation-resistant mechanisms and radiation sensibilization in cancer, which may further provide a theoretical and practical basis for personalized cancer therapy. PMID:27631970

  17. The future of liquid chromatography-mass spectrometry (LC-MS) in metabolic profiling and metabolomic studies for biomarker discovery

    PubMed Central

    Metz, Thomas O.; Zhang, Qibin; Page, Jason S.; Shen, Yufeng; Callister, Stephen J.; Jacobs, Jon M.; Smith, Richard D.

    2008-01-01

    SUMMARY The future utility of liquid chromatography-mass spectrometry (LC-MS) in metabolic profiling and metabolomic studies for biomarker discover will be discussed, beginning with a brief description of the evolution of metabolomics and the utilization of the three most popular analytical platforms in such studies: NMR, GC-MS, and LC-MS. Emphasis is placed on recent developments in high-efficiency LC separations, sensitive electrospray ionization approaches, and the benefits to incorporating both in LC-MS-based approaches. The advantages and disadvantages of various quantitative approaches are reviewed, followed by the current LC-MS-based tools available for candidate biomarker characterization and identification. Finally, a brief prediction on the future path of LC-MS-based methods in metabolic profiling and metabolomic studies is given. PMID:19177179

  18. Determining virus-host interactions and glycerol metabolism profiles in geographically diverse solar salterns with metagenomics

    PubMed Central

    Moller, Abraham G.

    2017-01-01

    Solar salterns are excellent model ecosystems for studying virus-microbial interactions because of their low microbial diversity, environmental stability, and high viral density. By using the power of CRISPR spacers to link viruses to their prokaryotic hosts, we explored virus-host interactions in geographically diverse salterns. Using taxonomic profiling, we identified hosts such as archaeal Haloquadratum, Halorubrum, and Haloarcula and bacterial Salinibacter, and we found that community composition related to not only salinity but also local environmental dynamics. Characterizing glycerol metabolism genes in these metagenomes suggested Halorubrum and Haloquadratum possess most dihydroxyacetone kinase genes while Salinibacter possesses most glycerol-3-phosphate dehydrogenase genes. Using two different methods, we detected fewer CRISPR spacers in Haloquadratum-dominated compared with Halobacteriaceae-dominated saltern metagenomes. After CRISPR detection, spacers were aligned against haloviral genomes to map virus to host. While most alignments for each saltern metagenome linked viruses to Haloquadratum walsbyi, there were also alignments indicating interactions with the low abundance taxa Haloarcula and Haloferax. Further examination of the dinucleotide and trinucleotide usage differences between paired viruses and their hosts confirmed viruses and hosts had similar nucleotide usage signatures. Detection of cas genes in the salterns supported the possibility of CRISPR activity. Taken together, our studies suggest similar virus-host interactions exist in different solar salterns and that the glycerol metabolism gene dihydroxyacetone kinase is associated with Haloquadratum and Halorubrum. PMID:28097058

  19. 1H NMR-based metabolic profiling for evaluating poppy seed rancidity and brewing.

    PubMed

    Jawień, Ewa; Ząbek, Adam; Deja, Stanisław; Łukaszewicz, Marcin; Młynarz, Piotr

    2015-12-01

    Poppy seeds are widely used in household and commercial confectionery. The aim of this study was to demonstrate the application of metabolic profiling for industrial monitoring of the molecular changes which occur during minced poppy seed rancidity and brewing processes performed on raw seeds. Both forms of poppy seeds were obtained from a confectionery company. Proton nuclear magnetic resonance (1H NMR) was applied as the analytical method of choice together with multivariate statistical data analysis. Metabolic fingerprinting was applied as a bioprocess control tool to monitor rancidity with the trajectory of change and brewing progressions. Low molecular weight compounds were found to be statistically significant biomarkers of these bioprocesses. Changes in concentrations of chemical compounds were explained relative to the biochemical processes and external conditions. The obtained results provide valuable and comprehensive information to gain a better understanding of the biology of rancidity and brewing processes, while demonstrating the potential for applying NMR spectroscopy combined with multivariate data analysis tools for quality control in food industries involved in the processing of oilseeds. This precious and versatile information gives a better understanding of the biology of these processes.

  20. Complete Genome Sequence and Comparative Metabolic Profiling of the Prototypical Enteroaggregative Escherichia coli Strain 042

    PubMed Central

    Chaudhuri, Roy R.; Sebaihia, Mohammed; Hobman, Jon L.; Webber, Mark A.; Leyton, Denisse L.; Goldberg, Martin D.; Cunningham, Adam F.; Scott-Tucker, Anthony; Ferguson, Paul R.; Thomas, Christopher M.; Frankel, Gad; Tang, Christoph M.; Dudley, Edward G.; Roberts, Ian S.; Rasko, David A.; Pallen, Mark J.; Parkhill, Julian; Nataro, James P.; Thomson, Nicholas R.; Henderson, Ian R.

    2010-01-01

    Background Escherichia coli can experience a multifaceted life, in some cases acting as a commensal while in other cases causing intestinal and/or extraintestinal disease. Several studies suggest enteroaggregative E. coli are the predominant cause of E. coli-mediated diarrhea in the developed world and are second only to Campylobacter sp. as a cause of bacterial-mediated diarrhea. Furthermore, enteroaggregative E. coli are a predominant cause of persistent diarrhea in the developing world where infection has been associated with malnourishment and growth retardation. Methods In this study we determined the complete genomic sequence of E. coli 042, the prototypical member of the enteroaggregative E. coli, which has been shown to cause disease in volunteer studies. We performed genomic and phylogenetic comparisons with other E. coli strains revealing previously uncharacterised virulence factors including a variety of secreted proteins and a capsular polysaccharide biosynthetic locus. In addition, by using Biolog™ Phenotype Microarrays we have provided a full metabolic profiling of E. coli 042 and the non-pathogenic lab strain E. coli K-12. We have highlighted the genetic basis for many of the metabolic differences between E. coli 042 and E. coli K-12. Conclusion This study provides a genetic context for the vast amount of experimental and epidemiological data published thus far and provides a template for future diagnostic and intervention strategies. PMID:20098708

  1. Hydrogen isotopic profile in the characterization of sugars. Influence of the metabolic pathway.

    PubMed

    Zhang, Ben-Li; Billault, Isabelle; Li, Xiaobao; Mabon, Françoise; Remaud, Gérald; Martin, Maryvonne L

    2002-03-13

    The site-specific natural hydrogen isotope ratios of plant metabolites determined by 2H nuclear magnetic resonance (SNIF-NMR method) can provide powerful criteria for inferring mechanistic and environmental effects on biosynthetic pathways. This work examines the potential of isotopic profiles for the main constituents of carbohydrates, glucose and fructose, to distinguish different photosynthetic pathways. An appropriate analytical strategy, involving three suitable isotopic probes, has been elaborated with a view to measuring simultaneously, in conditions devoid of isotopic perturbations, all (or nearly all) of the carbon-bound hydrogen isotope ratios. It is shown that the type of photosynthetic metabolism, either C3 (sugar beet, orange, and grape), C4 (maize and sugar cane), or CAM (pineapple), and the physiological status of the precursor plant exert strong influences on the deuterium distribution in the sugar molecules. Consequently, this isotopic fingerprint may be a rich source of information for the comparison of mechanisms in metabolic pathways. In addition, it can provide complementary criteria to ethanol as a probe for the origin of sugars.

  2. Determining virus-host interactions and glycerol metabolism profiles in geographically diverse solar salterns with metagenomics.

    PubMed

    Moller, Abraham G; Liang, Chun

    2017-01-01

    Solar salterns are excellent model ecosystems for studying virus-microbial interactions because of their low microbial diversity, environmental stability, and high viral density. By using the power of CRISPR spacers to link viruses to their prokaryotic hosts, we explored virus-host interactions in geographically diverse salterns. Using taxonomic profiling, we identified hosts such as archaeal Haloquadratum, Halorubrum, and Haloarcula and bacterial Salinibacter, and we found that community composition related to not only salinity but also local environmental dynamics. Characterizing glycerol metabolism genes in these metagenomes suggested Halorubrum and Haloquadratum possess most dihydroxyacetone kinase genes while Salinibacter possesses most glycerol-3-phosphate dehydrogenase genes. Using two different methods, we detected fewer CRISPR spacers in Haloquadratum-dominated compared with Halobacteriaceae-dominated saltern metagenomes. After CRISPR detection, spacers were aligned against haloviral genomes to map virus to host. While most alignments for each saltern metagenome linked viruses to Haloquadratum walsbyi, there were also alignments indicating interactions with the low abundance taxa Haloarcula and Haloferax. Further examination of the dinucleotide and trinucleotide usage differences between paired viruses and their hosts confirmed viruses and hosts had similar nucleotide usage signatures. Detection of cas genes in the salterns supported the possibility of CRISPR activity. Taken together, our studies suggest similar virus-host interactions exist in different solar salterns and that the glycerol metabolism gene dihydroxyacetone kinase is associated with Haloquadratum and Halorubrum.

  3. Volatile profiling reveals intracellular metabolic changes in Aspergillus parasiticus: veA regulates branched chain amino acid and ethanol metabolism

    PubMed Central

    2010-01-01

    Background Filamentous fungi in the genus Aspergillus produce a variety of natural products, including aflatoxin, the most potent naturally occurring carcinogen known. Aflatoxin biosynthesis, one of the most highly characterized secondary metabolic pathways, offers a model system to study secondary metabolism in eukaryotes. To control or customize biosynthesis of natural products we must understand how secondary metabolism integrates into the overall cellular metabolic network. By applying a metabolomics approach we analyzed volatile compounds synthesized by Aspergillus parasiticus in an attempt to define the association of secondary metabolism with other metabolic and cellular processes. Results Volatile compounds were examined using solid phase microextraction - gas chromatography/mass spectrometry. In the wild type strain Aspergillus parasiticus SU-1, the largest group of volatiles included compounds derived from catabolism of branched chain amino acids (leucine, isoleucine, and valine); we also identified alcohols, esters, aldehydes, and lipid-derived volatiles. The number and quantity of the volatiles produced depended on media composition, time of incubation, and light-dark status. A block in aflatoxin biosynthesis or disruption of the global regulator veA affected the volatile profile. In addition to its multiple functions in secondary metabolism and development, VeA negatively regulated catabolism of branched chain amino acids and synthesis of ethanol at the transcriptional level thus playing a role in controlling carbon flow within the cell. Finally, we demonstrated that volatiles generated by a veA disruption mutant are part of the complex regulatory machinery that mediates the effects of VeA on asexual conidiation and sclerotia formation. Conclusions 1) Volatile profiling provides a rapid, effective, and powerful approach to identify changes in intracellular metabolic networks in filamentous fungi. 2) VeA coordinates the biosynthesis of secondary

  4. Metabolic Profiling of Right Ventricular-Pulmonary Vascular Function Reveals Circulating Biomarkers of Pulmonary Hypertension

    PubMed Central

    Lewis, Gregory D.; Ngo, Debby; Hemnes, Anna R.; Farrell, Laurie; Domos, Carly; Pappagianopoulos, Paul P.; Dhakal, Bishnu P.; Souza, Amanda; Shi, Xu; Pugh, Meredith E.; Beloiartsev, Arkadi; Sinha, Sumita; Clish, Clary B.; Gerszten, Robert E.

    2016-01-01

    BACKGROUND Pulmonary hypertension and associated right ventricular (RV) dysfunction are important determinants of morbidity and mortality, which are optimally characterized by invasive hemodynamic measurements. OBJECTIVES This study sought to determine whether metabolite profiling could identify plasma signatures of right ventricular-pulmonary vascular (RV-PV) dysfunction. METHODS We measured plasma concentrations of 105 metabolites using targeted mass spectrometry in 71 individuals (discovery cohort) who underwent comprehensive physiological assessment with right-sided heart catheterization and radionuclide ventriculography at rest and during exercise. Our findings were validated in a second cohort undergoing invasive hemodynamic evaluations (n = 71), as well as in an independent cohort with or without known pulmonary arterial (PA) hypertension (n = 30). RESULTS In the discovery cohort, 21 metabolites were associated with 2 or more hemodynamic indicators of RV-PV function (i.e., resting right atrial pressure, mean PA pressure, pulmonary vascular resistance [PVR], and PVR and PA pressure-flow response [ΔPQ] during exercise). We identified novel associations of RV-PV dysfunction with circulating indoleamine 2,3-dioxygenase (IDO)–dependent tryptophan metabolites (TMs), tricarboxylic acid intermediates, and purine metabolites and confirmed previously described associations with arginine–nitric oxide metabolic pathway constituents. IDO-TM levels were inversely related to RV ejection fraction and were particularly well correlated with exercise PVR and ΔPQ. Multisite sampling demonstrated transpulmonary release of IDO-TMs. IDO-TMs also identified RV-PV dysfunction in a validation cohort with known risk factors for pulmonary hypertension and in patients with established PA hypertension. CONCLUSIONS Metabolic profiling identified reproducible signatures of RV-PV dysfunction, highlighting both new biomarkers and pathways for further functional characterization. PMID

  5. Health fair screening: the clinical utility of the comprehensive metabolic profile.

    PubMed

    Alpert, Jeffrey P; Greiner, Allen; Hall, Sandra

    2004-01-01

    Health fairs are a common method used by providers and health care organizations to provide screening tests, including comprehensive metabolic profiles (CMPs), to asymptomatic individuals. No national organizations currently recommend the complete CMP as a screening test for asymptomatic individuals in primary care settings. This study evaluated the value of CMPs in a health fair setting by measuring the ability of a health fair CMP to predict new medical diagnoses among residents of a sparsely populated rural county. Volunteer participants submitted fasting blood samples at a health fair conducted by a county health center in a county with 2,531 total residents. CMP values were determined to be "normal" or "abnormal" based on laboratory reference ranges and clinical judgment of the health center physicians. Medical records were reviewed 4 months later to determine if participants with abnormal CMP values had been diagnosed with new medical conditions as a result of the screening tests. Analysis was conducted to evaluate CMP test characteristics and determine whether demographic factors or specific CMP values predicted new medical diagnoses in the participants. Out of 478 health fair participants, 73 individuals had at least one abnormal CMP value. The most frequently occurring abnormal value was an elevated glucose level, with Hispanic participants significantly more likely to have this abnormality than whites. After all evaluation was completed, only about 1% of tested subjects had a new diagnosis as a result of the screening CMP test; most abnormal CMP tests did not result in a new diagnosis. The positive predictive value for an abnormal test resulting in a new medical diagnosis was 0.356. Comprehensive metabolic profiles have limited value as a screening tool in asymptomatic populations at health fairs.

  6. Prediction of glycated hemoglobin levels at 3 months after metabolic surgery based on the 7-day plasma metabolic profile.

    PubMed

    Kwon, Hyuk Nam; Lee, Yeon Ji; Kang, Ju-Hee; Choi, Ji-Ho; An, Yong Jin; Kang, Sunmi; Lee, Dae Hyun; Suh, Young Ju; Heo, Yoonseok; Park, Sunghyouk

    2014-01-01

    Metabolic surgery has been shown to provide better glycemic control for type 2 diabetes than conventional therapies. Still, the outcomes of the surgery are variable, and prognostic markers reflecting the metabolic changes by the surgery are yet to be established. NMR-based plasma metabolomics followed by multivariate regression was used to test the correlation between the metabolomic profile at 7-days after surgery and glycated hemoglobin (HbA1c) levels at 3-months (and up to 12 months with less patients), and to identify the relevant markers. Metabolomic profiles at 7-days could differentiate the patients according to the HbA1c improvement status at 3-months. The HbA1c values were predicted based on the metabolomics profile with partial least square regression, and found to be correlated with the observed values. Metabolite analysis suggested that 3-Hydroxybutyrate (3-HB) and glucose contributes to this prediction, and the [3-HB]/[glucose] exhibited a modest to good correlation with the HbA1c level at 3-months. The prediction of 3-month HbA1c using 7-day metabolomic profile and the suggested new criterion [3-HB]/[glucose] could augment current prognostic modalities and help clinicians decide if drug therapy is necessary.

  7. Graph methods for the investigation of metabolic networks in parasitology.

    PubMed

    Cottret, Ludovic; Jourdan, Fabien

    2010-08-01

    Recently, a way was opened with the development of many mathematical methods to model and analyze genome-scale metabolic networks. Among them, methods based on graph models enable to us quickly perform large-scale analyses on large metabolic networks. However, it could be difficult for parasitologists to select the graph model and methods adapted to their biological questions. In this review, after briefly addressing the problem of the metabolic network reconstruction, we propose an overview of the graph-based approaches used in whole metabolic network analyses. Applications highlight the usefulness of this kind of approach in the field of parasitology, especially by suggesting metabolic targets for new drugs. Their development still represents a major challenge to fight against the numerous diseases caused by parasites.

  8. Route profile analysis system and method

    DOEpatents

    Mullenhoff, Donald J.; Wilson, Stephen W.

    1986-01-01

    A system for recording terrain profile information is disclosed. The system accurately senses incremental distances traveled by a vehicle along with vehicle inclination, recording both with elapsed time. The incremental distances can subsequently be differentiated with respect to time to obtain acceleration. The acceleration can then be used by the computer to correct the sensed inclination.

  9. Some Innovative Methods to Improve Profiles Derivation

    ERIC Educational Resources Information Center

    Pei, Lai Kwan

    2008-01-01

    As the government aimed to provide appropriate education to all children (No Child Left Behind Act), it is important that the education providers can assess the performance of the students correctly so that they can provide the appropriate education for the students. Profile analysis is a very useful tool to interpret test scores and measure…

  10. Some Innovative Methods to Improve Profiles Derivation

    ERIC Educational Resources Information Center

    Pei, Lai Kwan

    2008-01-01

    As the government aimed to provide appropriate education to all children (No Child Left Behind Act), it is important that the education providers can assess the performance of the students correctly so that they can provide the appropriate education for the students. Profile analysis is a very useful tool to interpret test scores and measure…

  11. Route profile analysis system and method

    DOEpatents

    Mullenhoff, D.J.; Wilson, S.W.

    1982-07-29

    A system for recording terrain profile information is disclosed. The system accurately senses incremental distances traveled by a vehicle along with vehicle inclination, recording both with elapsed time. The incremental distances can subsequently be differentiated with respect to time to obtain acceleration. The computer acceleration can then be used to correct the sensed inclination.

  12. Metabolic profiles of planktonic and biofilm cells of Candida orthopsilosis.

    PubMed

    Pires, Regina Helena; Cataldi, Thaís Regiani; Franceschini, Livia Maria; Labate, Mônica Veneziano; Fusco-Almeida, Ana Marisa; Labate, Carlos Alberto; Palma, Mario Sérgio; Soares Mendes-Giannini, Maria José

    2016-10-01

    This study aims to understand which Candida orthopsilosis protein aids fungus adaptation upon its switching from planktonic growth to biofilm. Ion mobility separation within mass spectrometry analysis combination were used. Proteins mapped for different biosynthetic pathways showed that selective ribosome autophagy might occur in biofilms. Glucose, used as a carbon source in the glycolytic flux, changed to glycogen and trehalose. Candida orthopsilosis expresses proteins that combine a variety of mechanisms to provide yeasts with the means to adjust the catalytic properties of enzymes. Adjustment of the enzymes helps modulate the biosynthesis/degradation rates of the available nutrients, in order to control and coordinate the metabolic pathways that enable cells to express an adequate response to nutrient availability.

  13. Systems-level metabolic flux profiling identifies fatty acid synthesis as a target for antiviral therapy

    PubMed Central

    Munger, Joshua; Bennett, Bryson D; Parikh, Anuraag; Feng, Xiao-Jiang; McArdle, Jessica; Rabitz, Herschel A; Shenk, Thomas; Rabinowitz, Joshua D

    2010-01-01

    Viruses rely on the metabolic network of their cellular hosts to provide energy and building blocks for viral replication. We developed a flux measurement approach based on liquid chromatography–tandem mass spectrometry to quantify changes in metabolic activity induced by human cytomegalovirus (HCMV). This approach reliably elucidated fluxes in cultured mammalian cells by monitoring metabolome labeling kinetics after feeding cells 13C-labeled forms of glucose and glutamine. Infection with HCMV markedly upregulated flux through much of the central carbon metabolism, including glycolysis. Particularly notable increases occurred in flux through the tricarboxylic acid cycle and its efflux to the fatty acid biosynthesis pathway. Pharmacological inhibition of fatty acid biosynthesis suppressed the replication of both HCMV and influenza A, another enveloped virus. These results show that fatty acid synthesis is essential for the replication of two divergent enveloped viruses and that systems-level metabolic flux profiling can identify metabolic targets for antiviral therapy. PMID:18820684

  14. Plasma metabolic profiling analysis of nephrotoxicity induced by acyclovir using metabonomics coupled with multivariate data analysis.

    PubMed

    Zhang, Xiuxiu; Li, Yubo; Zhou, Huifang; Fan, Simiao; Zhang, Zhenzhu; Wang, Lei; Zhang, Yanjun

    2014-08-01

    Acyclovir (ACV) is an antiviral agent. However, its use is limited by adverse side effect, particularly by its nephrotoxicity. Metabonomics technology can provide essential information on the metabolic profiles of biofluids and organs upon drug administration. Therefore, in this study, mass spectrometry-based metabonomics coupled with multivariate data analysis was used to identify the plasma metabolites and metabolic pathways related to nephrotoxicity caused by intraperitoneal injection of low (50mg/kg) and high (100mg/kg) doses of acyclovir. Sixteen biomarkers were identified by metabonomics and nephrotoxicity results revealed the dose-dependent effect of acyclovir on kidney tissues. The present study showed that the top four metabolic pathways interrupted by acyclovir included the metabolisms of arachidonic acid, tryptophan, arginine and proline, and glycerophospholipid. This research proves the established metabonomic approach can provide information on changes in metabolites and metabolic pathways, which can be applied to in-depth research on the mechanism of acyclovir-induced kidney injury.

  15. Effect of tequila on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in healthy men.

    PubMed

    González-Ortiz, Manuel; Pascoe-González, Sara; Kam-Ramos, Angélica M; Martínez-Abundis, Esperanza

    2005-01-01

    The purpose of this study is to identify the effect of a low dose of tequila on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in healthy young men. An open clinical trial was carried out in eight healthy nonobese, young male volunteers. The study was divided in two phases. The first one evaluated metabolic changes, including insulin secretion and sensitivity due to acute administration of 30 ml of straight tequila. The second phase of the study evaluated metabolic effects due to the daily administration of 30 ml of tequila during 30 days. There were no significant metabolic changes after the single oral administration of 30 ml of straight tequila. After the administration of tequila during 30 days, a significant increase in homocysteine levels and a tendency to increase the glucose concentration and to decrease the insulin sensitivity were found. Detrimental metabolic changes were observed with the daily administration of 30 ml of tequila during 30 days.

  16. Metabolic Profiling in Association with Vascular Endothelial Cell Dysfunction Following Non-Toxic Cadmium Exposure

    PubMed Central

    Li, Xiaofei; Nong, Qingjiao; Mao, Baoyu; Pan, Xue

    2017-01-01

    This study aimed to determine the metabolic profile of non-toxic cadmium (Cd)-induced dysfunctional endothelial cells using human umbilical vein endothelial cells (HUVECs). HUVECs (n = 6 per group) were treated with 0, 1, 5, or 10 μM cadmium chloride (CdCl2) for 48 h. Cell phenotypes, including nitric oxide (NO) production, the inflammatory response, and oxidative stress, were evaluated in Cd-exposed and control HUVECs. Cd-exposed and control HUVECs were analysed using gas chromatography time-of-flight/mass spectrometry. Compared to control HUVECs, Cd-exposed HUVECs were dysfunctional, exhibiting decreased NO production, a proinflammatory state, and non-significant oxidative stress. Further metabolic profiling revealed 24 significantly-altered metabolites in the dysfunctional endothelial cells. The significantly-altered metabolites were involved in the impaired tricarboxylic acid (TCA) cycle, activated pyruvate metabolism, up-regulated glucogenic amino acid metabolism, and increased pyrimidine metabolism. The current metabolic findings further suggest that the metabolic changes linked to TCA cycle dysfunction, glycosylation of the hexosamine biosynthesis pathway (HBP), and compensatory responses to genomic instability and energy deficiency may be generally associated with dysfunctional phenotypes, characterized by decreased NO production, a proinflammatory state, and non-significant oxidative stress, in endothelial cells following non-toxic Cd exposure. PMID:28872622

  17. Metabolic profiling of hematopoietic stem and progenitor cells during proliferation and differentiation into red blood cells.

    PubMed

    Daud, Hasbullah; Browne, Susan; Al-Majmaie, Rasoul; Murphy, William; Al-Rubeai, Mohamed

    2016-01-25

    An understanding of the metabolic profile of cell proliferation and differentiation should support the optimization of culture conditions for hematopoietic stem and progenitor cell (HSPC) proliferation, differentiation, and maturation into red blood cells. We have evaluated the key metabolic parameters during each phase of HSPC culture for red blood cell production in serum-supplemented (SS) and serum-free (SF) conditions. A simultaneous decrease in growth rate, total protein content, cell size, and the percentage of cells in the S/G2 phase of cell cycle, as well as an increase in the percentage of cells with a CD71(-)/GpA(+) surface marker profile, indicates HSPC differentiation into red blood cells. Compared with proliferating HSPCs, differentiating HSPCs showed significantly lower glucose and glutamine consumption rates, lactate and ammonia production rates, and amino acid consumption and production rates in both SS and SF conditions. Furthermore, extracellular acidification was associated with late proliferation phase, suggesting a reduced cellular metabolic rate during the transition from proliferation to differentiation. Under both SS and SF conditions, cells demonstrated a high metabolic rate with a mixed metabolism of both glycolysis and oxidative phosphorylation (OXPHOS) in early and late proliferation, an increased dependence on OXPHOS activity during differentiation, and a shift to glycolytic metabolism only during maturation phase. These changes indicate that cell metabolism may have an important impact on the ability of HSPCs to proliferate and differentiate into red blood cells.

  18. Metabolic profil in a group of obese Moroccan children enrolled in schools in the city of Rabat

    PubMed Central

    Mouane, Nezha; Dekkaki, Imane Cherkaoui; Ettair, Said; Meskini, Toufik; Khalloufi, Nabil; Bouklouze, Aziz; Barkat, Amina

    2014-01-01

    Introduction To determine the metabolic profile in a group of obese children in Morocco. Methods The BMI, the waist circumference, the blood pressure and metabolic parameters in 73 children (37 obese and 36 normal) were compared. Results 80% of obese children had abdominal obesity (p <0.0001). For systolic blood pressure among children who have a higher value than the 95th percentile, 85.7% were obese and 14.3% children are normal children. For diastolic blood pressure, 83.34% of obese children had higher diastolic blood pressure values in the 95th percentile and 16.6% of normal children have a higher value than the 95th percentile (p=0.013). No obese child had hyperglycemia. The prevalence of metabolic syndrome was 21.6%. Conclusion Obesity is number one risk of cardiovascular disease for children. Early detection can help for an appropriate care. PMID:25977740

  19. The effect of combined inositol supplementation on maternal metabolic profile in pregnancies complicated by metabolic syndrome and obesity.

    PubMed

    Ferrari, Francesca; Facchinetti, Fabio; Ontiveros, Alejandra E; Roberts, Robyn P; Saade, Mia M; Blackwell, Sean C; Sibai, Baha M; Refuerzo, Jerrie S; Longo, Monica

    2016-10-01

    Myoinositol and D-chiroinositol improve insulin resistance in women with obesity and gestational diabetes and in postmenopausal women with metabolic syndrome. We previously reported that offspring born to hypertensive dams lacking endothelial nitric oxide synthase and fed a high-fat diet develop metabolic-like syndrome phenotype. The objective of the study was to investigate the effect of a mixture of myoinositol/D-chiroinositol supplementation during pregnancy on the maternal metabolic profile in pregnancies complicated by the metabolic-like syndrome and obesity using a pregnant mouse model. Female heterozygous endothelial nitric oxide synthase(-/+) mice with moderate hypertension were placed on a high-fat diet for 4 weeks to induce a metabolic-like syndrome phenotype. Similarly, wild-type C57BL/6 mice were placed on a high-fat diet for 4 weeks to induce a murine obesity model. Mice were then bred with wild-type males. On gestational day 1, dams were randomly allocated to receive either a mixture of myoinositol/D-chiroinositol in water (7.2/0.18 mg/mL, respectively) or water as control (placebo). At term (gestational day 18), maternal weights, systolic blood pressure, and a glucose tolerance test were obtained. Dams were then killed; pups and placentas were weighed and maternal blood collected. Serum levels of metabolic biomarkers relevant to diabetes and obesity (ghrelin, gastric inhibitory peptide, glucagon-like peptide 1, glucagon, insulin, leptin, resistin) were measured by a multiplex enzyme-linked immunosorbent assay. Analysis was done comparing metabolic-like syndrome-myoinositol/D-chiroinositol-treated vs metabolic-like syndrome-nontreated mice and obese-myoinositol/D-chiroinositol-treated vs obese nontreated mice. Mean systolic blood pressure was lower in metabolic-like syndrome pregnant mice treated with myoinositol/D-chiroinositol compared with placebo (P = .04), whereas there was no difference in systolic blood pressure between treated and placebo

  20. EnzDP: improved enzyme annotation for metabolic network reconstruction based on domain composition profiles.

    PubMed

    Nguyen, Nam-Ninh; Srihari, Sriganesh; Leong, Hon Wai; Chong, Ket-Fah

    2015-10-01

    Determining the entire complement of enzymes and their enzymatic functions is a fundamental step for reconstructing the metabolic network of cells. High quality enzyme annotation helps in enhancing metabolic networks reconstructed from the genome, especially by reducing gaps and increasing the enzyme coverage. Currently, structure-based and network-based approaches can only cover a limited number of enzyme families, and the accuracy of homology-based approaches can be further improved. Bottom-up homology-based approach improves the coverage by rebuilding Hidden Markov Model (HMM) profiles for all known enzymes. However, its clustering procedure relies firmly on BLAST similarity score, ignoring protein domains/patterns, and is sensitive to changes in cut-off thresholds. Here, we use functional domain architecture to score the association between domain families and enzyme families (Domain-Enzyme Association Scoring, DEAS). The DEAS score is used to calculate the similarity between proteins, which is then used in clustering procedure, instead of using sequence similarity score. We improve the enzyme annotation protocol using a stringent classification procedure, and by choosing optimal threshold settings and checking for active sites. Our analysis shows that our stringent protocol EnzDP can cover up to 90% of enzyme families available in Swiss-Prot. It achieves a high accuracy of 94.5% based on five-fold cross-validation. EnzDP outperforms existing methods across several testing scenarios. Thus, EnzDP serves as a reliable automated tool for enzyme annotation and metabolic network reconstruction. Available at: www.comp.nus.edu.sg/~nguyennn/EnzDP .

  1. Metabolic profiling reveals altered sugar and secondary metabolism in response to UGPase overexpression in Populus

    SciTech Connect

    Payyavula, Raja S.; Tschaplinski, Timothy J.; Jawdy, Sara; Sykes, Robert; Tuskan, Gerald A.; Kalluri, Udaya C.

    2014-10-07

    Background: UDP-glucose pyrophopharylase (UGPase) is a sugar metabolizing enzyme (E.C. 2.7.7.9) that catalyzes a reversible reaction of UDP-glucose and pyrophosphate from glucose-1-phosphate and uridine triphosphate glucose. UDP-glucose is a key intermediate sugar that is channeled to multiple metabolic pathways. The functional role of UGPase in woody plants such as Populus is poorly understood. Results: We characterized the functional role of UGPase in Populus deltoides by overexpressing a native gene. Overexpression of the native gene resulted in increased leaf area and leaf-to-shoot biomass ratio but decreased shoot and root growth. Metabolomic analyses showed that manipulation of UGPase results in perturbations in primary as well as secondary metabolism resulting in reduced sugar and starch levels and increased phenolics such as caffeoyl- and feruloyl conjugates. While cellulose and lignin levels in the cell walls were not significantly altered, the syringyl-to-guaiacyl ratio was significantly reduced. Conclusions: These results demonstrate that UGPase plays a key role in the tightly coupled primary and secondary metabolic pathways and perturbation in its function results in pronounced effects on growth and metabolism outside of cell wall biosynthesis of Populus.

  2. Metabolic profiling reveals altered sugar and secondary metabolism in response to UGPase overexpression in Populus

    DOE PAGES

    Payyavula, Raja S.; Tschaplinski, Timothy J.; Jawdy, Sara; ...

    2014-10-07

    Background: UDP-glucose pyrophopharylase (UGPase) is a sugar metabolizing enzyme (E.C. 2.7.7.9) that catalyzes a reversible reaction of UDP-glucose and pyrophosphate from glucose-1-phosphate and uridine triphosphate glucose. UDP-glucose is a key intermediate sugar that is channeled to multiple metabolic pathways. The functional role of UGPase in woody plants such as Populus is poorly understood. Results: We characterized the functional role of UGPase in Populus deltoides by overexpressing a native gene. Overexpression of the native gene resulted in increased leaf area and leaf-to-shoot biomass ratio but decreased shoot and root growth. Metabolomic analyses showed that manipulation of UGPase results in perturbations inmore » primary as well as secondary metabolism resulting in reduced sugar and starch levels and increased phenolics such as caffeoyl- and feruloyl conjugates. While cellulose and lignin levels in the cell walls were not significantly altered, the syringyl-to-guaiacyl ratio was significantly reduced. Conclusions: These results demonstrate that UGPase plays a key role in the tightly coupled primary and secondary metabolic pathways and perturbation in its function results in pronounced effects on growth and metabolism outside of cell wall biosynthesis of Populus.« less

  3. Comparison of STR profiling from low template DNA extracts with and without the consensus profiling method

    PubMed Central

    2012-01-01

    Background The consensus profiling method was introduced to overcome the exaggerated stochastic effects associated with low copy number DNA typing. However, little empirical evidence has been provided which shows that a consensus profile, derived from dividing a sample into separate aliquots and including only alleles seen at least twice, gives the most informative profile, compared to a profile obtained by amplifying the entire low template DNA extract in one reaction. Therefore, this study aimed to investigate the quality of consensus profiles compared to profiles obtained using the whole low template extract for amplification. Methods A total of 100 pg and 25 pg DNA samples were amplified with the PowerPlex® ESI 16 Kits using 30 or 34 PCR cycles. A total of 100 pg and 25 pg DNA samples were then divided into three aliquots for a 34-cycle PCR and a consensus profile derived that included alleles that appeared in at least two of the replicates. Profiles from the non-split samples were compared to the consensus profiles focusing on peak heights, allele drop out, locus drop out and allele drop in. Results Performing DNA profiling on non-split extracts produced profiles with a higher percentage of correct loci compared to the consensus profiling technique. Consensus profiling did eliminate any spurious alleles from the final profile. However, there was a notable increase in allele and locus drop out when a LTDNA sample was divided prior to amplification. Conclusions The loss of information that occurs when a sample is split for amplification indicates that consensus profiling may not be producing the most informative DNA profile for samples where the template amount is limited. PMID:22748106

  4. Metabolic profile of injured human spinal cord determined using surface microdialysis.

    PubMed

    Chen, Suliang; Phang, Isaac; Zoumprouli, Argyro; Papadopoulos, Marios C; Saadoun, Samira

    2016-12-01

    The management of patients having traumatic spinal cord injury would benefit from understanding and monitoring of spinal cord metabolic states. We hypothesized that the metabolism of the injured spinal cord could be visualized using Kohonen self-organizing maps. Sixteen patients with acute, severe spinal cord injuries were studied. Starting within 72 h of the injury, and for up to a week, we monitored the injury site hourly for tissue glucose, lactate, pyruvate, glutamate, and glycerol using microdialysis as well as intraspinal pressure and spinal cord perfusion pressure. A Kohonen map, which is an unsupervised, self-organizing topology-preserving neural network, was used to analyze 3366 h of monitoring data. We first visualized the different spinal cord metabolic states. Our data show that the injured cord assumes one or more of four metabolic states. On the basis of their metabolite profiles, we termed these states near-normal, ischemic, hypermetabolic, and distal. We then visualized how patients' intraspinal pressure and spinal cord perfusion pressure affect spinal cord metabolism. This revealed that for more than 60% of the time, spinal cord metabolism is patient-specific; periods of high intraspinal pressure or low perfusion pressure are not associated with specific spinal cord metabolic patterns. Finally, we determined relationships between spinal cord metabolism and neurological status. Patients with complete deficits have shorter periods of near-normal spinal cord metabolic states (7 ± 4% vs. 58 ± 12%, p < 0.01, mean ± standard error) and more variable injury site metabolic responses (metabolism spread in 70 ± 11 vs. 40 ± 6 hexagons, p < 0.05), compared with patients who have incomplete neurological deficits. We conclude that Kohonen maps allow us to visualize the metabolic responses of the injured spinal cord and may thus aid us in treating patients with acute spinal cord injuries.

  5. Suicide Bombers: Profiles, Methods and Techniques

    DTIC Science & Technology

    2007-01-01

    in the makeup of suicide terrorists is “just a myth” and that religious convictions, political sentiments, and social conditions are of secondary...most terrorists are young and that their actions and psychological makeup vary according to social and cultural conditions.22 Professor Ian Ross...of the University of Baltimore provides an alternate view and believes that profiling is possible by combining social factors and psychological

  6. Preliminary Investigation of Profiling Tools and Methods

    DTIC Science & Technology

    2011-06-01

    decades, profiling has gained popularity in investigations as well as popular culture through its portrayal in the media and fictional work (Crighton, 2010...such anecdote indicates that: “A series of 11 sexual assaults during a 35-day period in 1998 were attributed to a single offender. Extensive media ...Press. [29] Petty, R. E., Briñol, P., & Priester, J. R. (2009). Mass media attitude change: Implications of the Elaboration Likelihood Model of

  7. Metabolic profiling of body fluids and multivariate data analysis.

    PubMed

    Trezzi, Jean-Pierre; Jäger, Christian; Galozzi, Sara; Barkovits, Katalin; Marcus, Katrin; Mollenhauer, Brit; Hiller, Karsten

    2017-01-01

    Metabolome analyses of body fluids are challenging due pre-analytical variations, such as pre-processing delay and temperature, and constant dynamical changes of biochemical processes within the samples. Therefore, proper sample handling starting from the time of collection up to the analysis is crucial to obtain high quality samples and reproducible results. A metabolomics analysis is divided into 4 main steps: 1) Sample collection, 2) Metabolite extraction, 3) Data acquisition and 4) Data analysis. Here, we describe a protocol for gas chromatography coupled to mass spectrometry (GC-MS) based metabolic analysis for biological matrices, especially body fluids. This protocol can be applied on blood serum/plasma, saliva and cerebrospinal fluid (CSF) samples of humans and other vertebrates. It covers sample collection, sample pre-processing, metabolite extraction, GC-MS measurement and guidelines for the subsequent data analysis. Advantages of this protocol include: •Robust and reproducible metabolomics results, taking into account pre-analytical variations that may occur during the sampling process•Small sample volume required•Rapid and cost-effective processing of biological samples•Logistic regression based determination of biomarker signatures for in-depth data analysis.

  8. Metabolic profiling of strawberry (Fragaria x ananassa Duch.) during fruit development and maturation.

    PubMed

    Zhang, Juanjuan; Wang, Xin; Yu, Oliver; Tang, Juanjuan; Gu, Xungang; Wan, Xiaochun; Fang, Congbing

    2011-01-01

    Strawberry (Fragaria × ananassa Duch), a fruit of economic and nutritional importance, is also a model species for fleshy fruits and genomics in Rosaceae. Strawberry fruit quality at different harvest stages is a function of the fruit's metabolite content, which results from physiological changes during fruit growth and ripening. In order to investigate strawberry fruit development, untargeted (GC-MS) and targeted (HPLC) metabolic profiling analyses were conducted. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were employed to explore the non-polar and polar metabolite profiles from fruit samples at seven developmental stages. Different cluster patterns and a broad range of metabolites that exerted influence on cluster formation of metabolite profiles were observed. Significant changes in metabolite levels were found in both fruits turning red and fruits over-ripening in comparison with red-ripening fruits. The levels of free amino acids decreased gradually before the red-ripening stage, but increased significantly in the over-ripening stage. Metabolite correlation and network analysis revealed the interdependencies of individual metabolites and metabolic pathways. Activities of several metabolic pathways, including ester biosynthesis, the tricarboxylic acid cycle, the shikimate pathway, and amino acid metabolism, shifted during fruit growth and ripening. These results not only confirmed published metabolic data but also revealed new insights into strawberry fruit composition and metabolite changes, thus demonstrating the value of metabolomics as a functional genomics tool in characterizing the mechanism of fruit quality formation, a key developmental stage in most economically important fruit crops.

  9. Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population

    EPA Science Inventory

    Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population David J. Thomas – ISTD, NHEERL Edward F. Hudgens – EHPD, NHEERL John Rogers - Westat Relations between intensity of arsenic exposure from home tap water and levels of inorganic As ...

  10. Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population

    EPA Science Inventory

    Biological and behavioral modifiers of urinary arsenic metabolic profiles in a U.S. population David J. Thomas – ISTD, NHEERL Edward F. Hudgens – EHPD, NHEERL John Rogers - Westat Relations between intensity of arsenic exposure from home tap water and levels of inorganic As ...

  11. Yogurt consumption is associated with better diet quality and metabolic profile in American men and women

    USDA-ARS?s Scientific Manuscript database

    Low-fat dairy products may be beneficial for health, but few studies have specifically focused on yogurt. We examined whether yogurt consumption was associated with better dietary patterns, diet quality, and metabolic profile. This cross-sectional study included the adults (n=6526) participating in ...

  12. Multi-omic profiles of hepatic metabolism in TPN-fed preterm pigs

    USDA-ARS?s Scientific Manuscript database

    New generation lipid emulsions comprised of fish oil or blends of soybean/fish/medium chain triglyceride/olive oil are emerging that result in favorable clinical metabolic outcomes in pediatric populations. Our aim was to characterize the lipidodomic, metabolomic, and transcriptomic profiles these ...

  13. Association of altered cardiac autonomic function with psychopathology and metabolic profiles in schizophrenia.

    PubMed

    Chung, Ming-Shun; Yang, Albert C; Lin, Yu-Chung; Lin, Chieh-Nan; Chang, Fang-Rong; Shen, Shu-hua; Ouyang, Wen-Chen; Loh, El-Wui; Chiu, Hsien-Jane

    2013-12-30

    Schizophrenia has been associated with autonomic dysregulation and increased cardiovascular co-morbidity. We hypothesised that autonomic dysregulation in patients with schizophrenia is associated with psychopathology and metabolic profiles. In this study, we aimed to evaluate psychopathology, comprehensive metabolic profiles and cardiac autonomic function using heart-rate variability (HRV) analysis in patients with schizophrenia. A total of 94 patients with schizophrenia and 51 healthy controls were recruited. Each patient underwent a physical examination, laboratory tests and rating scale evaluation, and all subjects underwent a 1-h electrocardiogram monitoring. Analysis of variance was used to compare demographic and HRV variables between control and patient groups. We applied multiple regression analysis with backward selection to examine the association between HRV indices and demographic, metabolic and psychopathology profiles. A decreased HRV was found in patient groups, compared to controls. Reduced vagal-related and complexity domain of HRV indices in patient groups were correlated with increased body mass indices, diastolic pressure, triglycerides, high- and low-density lipoprotein and severity of psychosis mainly in the negative symptom domain. This study provides evidence that altered autonomic function is associated with both psychopathology and metabolic profiles in patients with schizophrenia. These findings may warrant future research in using HRV as objective markers to monitor cardiovascular health and the severity of psychosis in patients with schizophrenia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Observational study of lipid profile and LDL particle size in patients with metabolic syndrome

    PubMed Central

    2011-01-01

    Background The atherogenic lipoprotein phenotype is characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein cholesterol (HDLc), and the prevalence of small, dense-low density lipoprotein cholesterol (LDLc) particles. The aim of this study was to establish the importance of LDL particle size measurement by gender in a group of patients with Metabolic Syndrome (MS) attending at a Cardiovascular Risk Unit in Primary Care and their classification into phenotypes. Subjects and methods One hundred eighty-five patients (93 men and 92 women) from several areas in the South of Spain, for a period of one year in a health centre were studied. Laboratory parameters included plasma lipids, lipoproteins, low-density lipoprotein size and several atherogenic rates were determinated. Results We found differences by gender between anthropometric parameters, blood pressure and glucose measures by MS status. Lipid profile was different in our two study groups, and gender differences in these parameters within each group were also remarkable, in HDLc and Apo A-I values. According to LDL particle size, we found males had smaller size than females, and patients with MS had also smaller than those without MS. We observed inverse relationship between LDL particle size and triglycerides in patients with and without MS, and the same relationship between all atherogenic rates in non-MS patients. When we considered our population in two classes of phenotypes, lipid profile was worse in phenotype B. Conclusion In conclusion, we consider worthy the measurement of LDL particle size due to its relationship with lipid profile and cardiovascular risk. PMID:21936888

  15. Inactivation and changes in metabolic profile of selected foodborne bacteria by 460 nm LED illumination.

    PubMed

    Kumar, Amit; Ghate, Vinayak; Kim, Min-Jeong; Zhou, Weibiao; Khoo, Gek Hoon; Yuk, Hyun-Gyun

    2017-05-01

    The objective of this study was to investigate the effect of 460 nm light-emitting diode (LED) on the inactivation of foodborne bacteria. Additionally, the change in the endogenous metabolic profile of LED illuminated cells was analyzed to understand the bacterial response to the LED illumination. Six different species of bacteria (Bacillus cereus, Listeria monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, Pseudomonas aeruginosa and Salmonella Typhimurium) were illuminated with 460 nm LED to a maximum dose of 4080 J/cm(2) at 4, 10 and 25 °C. Inactivation curves were modeled using Hom model. Metabolic profiling of the non-illuminated and illuminated cells was performed using a Liquid chromatography-mass spectrometry system. Results indicate that the 460 nm LED significantly (p < 0.05) reduced the populations of all six bacterial species. For example, the population of S. aureus reached below detection limit within 7 h. B. cereus was most resistant to photo-inactivation and exhibited about 3-log reduction in 9 h. Metabolic profiling of the illuminated cells indicated that several metabolites e.g. 11-deoxycortisol, actinonin, coformycin, tyramine, chitobiose etc. were regulated during LED illumination. These results elucidate the effectiveness of 460 nm LED against foodborne bacteria and hence, its suitability as a novel antimicrobial control method to ensure food safety.

  16. Metabolic Profile of Wound-Induced Changes in Primary Carbon Metabolism in Sugarbeet Root

    USDA-ARS?s Scientific Manuscript database

    Injury to plant products induces respiration rate and increases the demand for respiratory substrates. Alterations in primary carbon metabolism are likely to support the elevated demand for respiratory substrates, although the nature of these alterations is unknown. To gain insight into the metabo...

  17. [Barometer of type 2 diabetes in primary care. Metabolic control, styles of life and morbidity profile].

    PubMed

    Pérez-Manchón, David; Rodríguez-Álvarez, María Lorena; Alcívar-Arteaga, Claudia; Redondo-Pico, Mercedes; Ramos-Quirós, Elena

    2016-12-28

    Knowing the profile of cardiovascular morbidity, degree of control and lifestyles in type 2 diabetes. Randomized multicenter cross-sectional study conducted in 2015 in primary care with 129 diabetics. It included sociodemographic variables, microvascular and macrovascular complications, organic damage, comorbidity and lifestyles of smoking, exercise and adherence to Mediterranean diet. Metabolic control was assessed with the latest annual glycosylated haemoglobin. 57% were men and 43% women. Metabolic control was acceptable (HbAc1%, 7.15%) without differences by town. 74.4% had cardiovascular comorbidity and the 99.2% risk factors. 23% were smokers and 41% sedentary with a 56% adherence to Mediterranean diet. The cardiometabolic profile of diabetes includes retinopathy, peripheral arterial disease, comorbidity of hypertension and cardiovascular risk factors. Individual or group health education in self-care and healthy lifestyles can improve metabolic control. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  18. Comparison of STR profiling from low template DNA extracts with and without the consensus profiling method.

    PubMed

    Grisedale, Kelly S; van Daal, Angela

    2012-07-02

    The consensus profiling method was introduced to overcome the exaggerated stochastic effects associated with low copy number DNA typing. However, little empirical evidence has been provided which shows that a consensus profile, derived from dividing a sample into separate aliquots and including only alleles seen at least twice, gives the most informative profile, compared to a profile obtained by amplifying the entire low template DNA extract in one reaction. Therefore, this study aimed to investigate the quality of consensus profiles compared to profiles obtained using the whole low template extract for amplification. A total of 100 pg and 25 pg DNA samples were amplified with the PowerPlex® ESI 16 Kits using 30 or 34 PCR cycles. A total of 100 pg and 25 pg DNA samples were then divided into three aliquots for a 34-cycle PCR and a consensus profile derived that included alleles that appeared in at least two of the replicates. Profiles from the non-split samples were compared to the consensus profiles focusing on peak heights, allele drop out, locus drop out and allele drop in. Performing DNA profiling on non-split extracts produced profiles with a higher percentage of correct loci compared to the consensus profiling technique. Consensus profiling did eliminate any spurious alleles from the final profile. However, there was a notable increase in allele and locus drop out when a LTDNA sample was divided prior to amplification. The loss of information that occurs when a sample is split for amplification indicates that consensus profiling may not be producing the most informative DNA profile for samples where the template amount is limited.

  19. Obesity, metabolic profile, and inhibition failure: Young women under scrutiny.

    PubMed

    Catoira, N P; Tapajóz, F; Allegri, R F; Lajfer, J; Rodríguez Cámara, M J; Iturry, M L; Castaño, G O

    2016-04-01

    The prevalence of obesity, as well as evidence about this pathology as a risk factor for cognitive decline and dementia in the elderly, is increasing worldwide. Executive functions have been found to be compromised in most studies, although the specific results are dissimilar. Obese young women constitute an interesting study and intervention group, having been found to be unaffected by age and hormonal negative effects on cognition and considering that their health problems affect not only themselves but their families and offspring. The objective of the present study was to compare the executive performance of obese young women with that of a healthy control group. A cross-sectional study was done among premenopausal women from a public hospital in Buenos Aires. The sample comprised 113 participants (32 healthy controls and 81 obese women), who were evaluated for depressive and anxiety symptoms (Beck Depression Inventory-II and State-Trait Anxiety Inventory) and executive functioning (Trail-Making Test B, Stroop Color and Word Test, Wisconsin Card Sorting Test, and verbal fluency test). Statistical analysis was done by using the SPSS version 20.0 software. Among executive functions, a significant difference was found between groups in inhibition (p<0.01). No correlation was found between psychopathologic measures and Stroop Test Interference results. We found slight correlations between Stroop Test Interference results, waist circumference, fat mass and HDL-cholesterol. In obese group, there was a negative slightly correlation between this cognitive test and 2h post-load glucose level. Inhibition was decreased in our obese young women group, and glucose/lipid metabolism may be involved in this association. The cognitive impairment is comparable with that described in addictive conditions. Our conclusions support the concept of multidisciplinary management of obese patients from the time of diagnosis. Detecting and understanding cognitive dysfunction in this

  20. Metabolic profiling of alternative NAD biosynthetic routes in mouse tissues.

    PubMed

    Mori, Valerio; Amici, Adolfo; Mazzola, Francesca; Di Stefano, Michele; Conforti, Laura; Magni, Giulio; Ruggieri, Silverio; Raffaelli, Nadia; Orsomando, Giuseppe

    2014-01-01

    NAD plays essential redox and non-redox roles in cell biology. In mammals, its de novo and recycling biosynthetic pathways encompass two independent branches, the "amidated" and "deamidated" routes. Here we focused on the indispensable enzymes gating these two routes, i.e. nicotinamide mononucleotide adenylyltransferase (NMNAT), which in mammals comprises three distinct isozymes, and NAD synthetase (NADS). First, we measured the in vitro activity of the enzymes, and the levels of all their substrates and products in a number of tissues from the C57BL/6 mouse. Second, from these data, we derived in vivo estimates of enzymes'rates and quantitative contributions to NAD homeostasis. The NMNAT activity, mainly represented by nuclear NMNAT1, appears to be high and nonrate-limiting in all examined tissues, except in blood. The NADS activity, however, appears rate-limiting in lung and skeletal muscle, where its undetectable levels parallel a relative accumulation of the enzyme's substrate NaAD (nicotinic acid adenine dinucleotide). In all tissues, the amidated NAD route was predominant, displaying highest rates in liver and kidney, and lowest in blood. In contrast, the minor deamidated route showed higher relative proportions in blood and small intestine, and higher absolute values in liver and small intestine. Such results provide the first comprehensive picture of the balance of the two alternative NAD biosynthetic routes in different mammalian tissues under physiological conditions. This fills a gap in the current knowledge of NAD biosynthesis, and provides a crucial information for the study of NAD metabolism and its role in disease.

  1. Metabolic Profiles in Ovine Carotid Arteries with Developmental Maturation and Long-Term Hypoxia

    PubMed Central

    Goyal, Ravi; Longo, Lawrence D.

    2015-01-01

    Background Long-term hypoxia (LTH) is an important stressor related to health and disease during development. At different time points from fetus to adult, we are exposed to hypoxic stress because of placental insufficiency, high-altitude residence, smoking, chronic anemia, pulmonary, and heart disorders, as well as cancers. Intrauterine hypoxia can lead to fetal growth restriction and long-term sequelae such as cognitive impairments, hypertension, cardiovascular disorders, diabetes, and schizophrenia. Similarly, prolonged hypoxic exposure during adult life can lead to acute mountain sickness, chronic fatigue, chronic headache, cognitive impairment, acute cerebral and/or pulmonary edema, and death. Aim LTH also can lead to alteration in metabolites such as fumarate, 2-oxoglutarate, malate, and lactate, which are linked to epigenetic regulation of gene expression. Importantly, during the intrauterine life, a fetus is under a relative hypoxic environment, as compared to newborn or adult. Thus, the changes in gene expression with development from fetus to newborn to adult may be as a consequence of underlying changes in the metabolic profile because of the hypoxic environment along with developmental maturation. To examine this possibility, we examined the metabolic profile in carotid arteries from near-term fetus, newborn, and adult sheep in both normoxic and long-term hypoxic acclimatized groups. Results Our results demonstrate that LTH differentially regulated glucose metabolism, mitochondrial metabolism, nicotinamide cofactor metabolism, oxidative stress and antioxidants, membrane lipid hydrolysis, and free fatty acid metabolism, each of which may play a role in genetic-epigenetic regulation. PMID:26110419

  2. Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages

    PubMed Central

    Hollenbaugh, Joseph A.; Montero, Catherine; Schinazi, Raymond F.; Munger, Joshua; Kim, Baek

    2016-01-01

    We evaluated cellular metabolism profiles of HIV-1 and HIV-2 infected primary human monocyte-derived macrophages (MDMs). First, HIV-2 GL-AN displays faster production kinetics and greater amounts of virus as compared to HIV-1s: YU-2, 89.6 and JR-CSF. Second, quantitative LC–MS/MS metabolomics analysis demonstrates very similar metabolic profiles in glycolysis and TCA cycle metabolic intermediates between HIV-1 and HIV-2 infected macrophages, with a few notable exceptions. The most striking metabolic change in MDMs infected with HIV-2 relative to HIV-1-infected MDMs was the increased levels of quinolinate, a metabolite in the tryptophan catabolism pathway that has been linked to HIV/AIDS pathogenesis. Third, both HIV-1 and HIV-2 infected MDMs showed elevated levels of ribose-5-phosphate, a key metabolic component in nucleotide biosynthesis. Finally, HIV-2 infected MDMs display increased dNTP concentrations as predicted by Vpx-mediated SAMHD1 degradation. Collectively, these data show differential metabolic changes during HIV-1 and HIV-2 infection of macrophages. PMID:26895248

  3. Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions.

    PubMed

    Rao, Vijayaraghava T S; Khan, Damla; Cui, Qiao-Ling; Fuh, Shih-Chieh; Hossain, Shireen; Almazan, Guillermina; Multhaup, Gerhard; Healy, Luke M; Kennedy, Timothy E; Antel, Jack P

    2017-01-01

    Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress, adult human oligodendrocytes reduce overall energy production rate impacting the capacity to maintain myelination. Here, we directly compare the metabolic profiles of oligodendrocytes derived from adult rat brain with oligodendrocytes newly differentiated in vitro from oligodendrocyte progenitor cells obtained from the post natal rat brain, under both optimal culture and metabolic stress (low/no glucose) conditions. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Our findings indicate that under optimal conditions, adult rat oligodendrocytes preferentially use glycolysis whereas newly differentiated post natal rat oligodendrocytes, and the oligodendrocyte progenitor cells from which they are derived, mainly utilize oxidative phosphorylation to produce ATP. Metabolic stress increases the rate of ATP production via oxidative phosphorylation and significantly reduces glycolysis in adult oligodendrocytes. The rate of ATP production was relatively unchanged in newly differentiated post natal oligodendrocytes under these stress conditions, while it was significantly reduced in oligodendrocyte progenitor cells. Our study indicates that both age and maturation influence the metabolic profile under optimal and stressed conditions, emphasizing the need to consider these variables for in vitro studies that aim to model adult human disease.

  4. Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors

    PubMed Central

    Daemen, Anneleen; Peterson, David; Sahu, Nisebita; McCord, Ron; Du, Xiangnan; Liu, Bonnie; Kowanetz, Katarzyna; Hong, Rebecca; Moffat, John; Gao, Min; Boudreau, Aaron; Mroue, Rana; Corson, Laura; O’Brien, Thomas; Qing, Jing; Sampath, Deepak; Merchant, Mark; Yauch, Robert; Manning, Gerard; Settleman, Jeffrey; Hatzivassiliou, Georgia; Evangelista, Marie

    2015-01-01

    Although targeting cancer metabolism is a promising therapeutic strategy, clinical success will depend on an accurate diagnostic identification of tumor subtypes with specific metabolic requirements. Through broad metabolite profiling, we successfully identified three highly distinct metabolic subtypes in pancreatic ductal adenocarcinoma (PDAC). One subtype was defined by reduced proliferative capacity, whereas the other two subtypes (glycolytic and lipogenic) showed distinct metabolite levels associated with glycolysis, lipogenesis, and redox pathways, confirmed at the transcriptional level. The glycolytic and lipogenic subtypes showed striking differences in glucose and glutamine utilization, as well as mitochondrial function, and corresponded to differences in cell sensitivity to inhibitors of glycolysis, glutamine metabolism, lipid synthesis, and redox balance. In PDAC clinical samples, the lipogenic subtype associated with the epithelial (classical) subtype, whereas the glycolytic subtype strongly associated with the mesenchymal (QM-PDA) subtype, suggesting functional relevance in disease progression. Pharmacogenomic screening of an additional ∼200 non-PDAC cell lines validated the association between mesenchymal status and metabolic drug response in other tumor indications. Our findings highlight the utility of broad metabolite profiling to predict sensitivity of tumors to a variety of metabolic inhibitors. PMID:26216984

  5. Path finding methods accounting for stoichiometry in metabolic networks

    PubMed Central

    2011-01-01

    Graph-based methods have been widely used for the analysis of biological networks. Their application to metabolic networks has been much discussed, in particular noting that an important weakness in such methods is that reaction stoichiometry is neglected. In this study, we show that reaction stoichiometry can be incorporated into path-finding approaches via mixed-integer linear programming. This major advance at the modeling level results in improved prediction of topological and functional properties in metabolic networks. PMID:21619601

  6. Tissue metabolic profiling of human gastric cancer assessed by (1)H NMR.

    PubMed

    Wang, Huijuan; Zhang, Hailong; Deng, Pengchi; Liu, Chunqi; Li, Dandan; Jie, Hui; Zhang, Hu; Zhou, Zongguang; Zhao, Ying-Lan

    2016-06-29

    Gastric cancer is the fourth most common cancer and the second most deadly cancer worldwide. Study on molecular mechanisms of carcinogenesis will play a significant role in diagnosing and treating gastric cancer. Metabolic profiling may offer the opportunity to understand the molecular mechanism of carcinogenesis and help to identify the potential biomarkers for the early diagnosis of gastric cancer. In this study, we reported the metabolic profiling of tissue samples on a large cohort of human gastric cancer subjects (n = 125) and normal controls (n = 54) based on (1)H nuclear magnetic resonance ((1)H NMR) together with multivariate statistical analyses (PCA, PLS-DA, OPLS-DA and ROC curve). The OPLS-DA model showed adequate discrimination between cancer tissues and normal controls, and meanwhile, the model excellently discriminated the stage-related of tissue samples (stage I, 30; stage II, 46; stage III, 37; stage IV, 12) and normal controls. A total of 48 endogenous distinguishing metabolites (VIP > 1 and p < 0.05) were identified, 13 of which were changed with the progression of gastric cancer. These modified metabolites revealed disturbance of glycolysis, glutaminolysis, TCA, amino acids and choline metabolism, which were correlated with the occurrence and development of human gastric cancer. The receiver operating characteristic diagnostic AUC of OPLS-DA model between cancer tissues and normal controls was 0.945. And the ROC curves among different stages cancer subjects and normal controls were gradually improved, the corresponding AUC values were 0.952, 0.994, 0.998 and 0.999, demonstrating the robust diagnostic power of this metabolic profiling approach. As far as we know, the present study firstly identified the differential metabolites in various stages of gastric cancer tissues. And the AUC values were relatively high. So these results suggest that the metabolic profiling of gastric cancer tissues has great potential in detecting this

  7. Metabolic profiling of biofilm bacteria known to cause microbial influenced corrosion.

    PubMed

    Beale, D J; Morrison, P D; Key, C; Palombo, E A

    2014-01-01

    This study builds upon previous research that demonstrated the simplicity of obtaining metabolite profiles of bacteria in urban water networks, by using the metabolic profile of bacteria extracted from a reticulation pipe biofilm, which is known to cause microbial influenced corrosion (MIC). The extracellular metabolites of the isolated bacteria, and those bacteria in consortium, were analysed in isolation, and after exposure to low levels of copper. Applying chemometric analytical methodologies to the metabolomic data, we were able to better understand the profile of the isolated biofilm bacteria, which were differentiated according to their activity and copper exposure. It was found that the metabolic activity of the isolated bacteria and the bacteria in consortium varied according to the bacterium's ability to metabolise copper. This demonstrates the power of metabolomic techniques for the discrimination of water reticulation biofilms comprising similar bacteria in consortium, but undergoing different physico-chemical activities, such as corrosion and corrosion inhibition.

  8. Gas chromatography-mass spectrometry-based metabolic profiling of cerebrospinal fluid from epileptic dogs.

    PubMed

    Hasegawa, Tetsuya; Sumita, Maho; Horitani, Yusuke; Tamai, Reo; Tanaka, Katsuhiro; Komori, Masayuki; Takenaka, Shigeo

    2014-04-01

    Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy.

  9. Gas Chromatography-Mass Spectrometry-Based Metabolic Profiling of Cerebrospinal Fluid from Epileptic Dogs

    PubMed Central

    HASEGAWA, Tetsuya; SUMITA, Maho; HORITANI, Yusuke; TAMAI, Reo; TANAKA, Katsuhiro; KOMORI, Masayuki; TAKENAKA, Shigeo

    2013-01-01

    ABSTRACT Epilepsy is a common neurological disorder with seizures, but diagnostic approaches in veterinary clinics remain limited. Cerebrospinal fluid (CSF) is a body fluid used for diagnosis in veterinary medicine. In this study, we explored canine epilepsy diagnostic biomarkers using gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling of CSF and multivariate data analysis. Profiles for subjects with idiopathic epilepsy differed significantly from those of healthy controls and subjects with symptomatic epilepsy. Among 60 identified metabolites, the levels of 20 differed significantly among the three groups. Glutamic acid was significantly increased in idiopathic epilepsy, and some metabolites including ascorbic acid were changed in both forms of epilepsy. These findings show that metabolic profiles of CSF differ between idiopathic and symptomatic epilepsy and that metabolites including glutamic acid and ascorbic acid in CSF may be useful for diagnosis of canine epilepsy. PMID:24334864

  10. A Comprehensive Metabolic Profile of Cultured Astrocytes Using Isotopic Transient Metabolic Flux Analysis and 13C-Labeled Glucose

    PubMed Central

    Amaral, Ana I.; Teixeira, Ana P.; Håkonsen, Bjørn I.; Sonnewald, Ursula; Alves, Paula M.

    2011-01-01

    Metabolic models have been used to elucidate important aspects of brain metabolism in recent years. This work applies for the first time the concept of isotopic transient 13C metabolic flux analysis (MFA) to estimate intracellular fluxes in primary cultures of astrocytes. This methodology comprehensively explores the information provided by 13C labeling time-courses of intracellular metabolites after administration of a 13C-labeled substrate. Cells were incubated with medium containing [1-13C]glucose for 24 h and samples of cell supernatant and extracts collected at different time points were then analyzed by mass spectrometry and/or high performance liquid chromatography. Metabolic fluxes were estimated by fitting a carbon labeling network model to isotopomer profiles experimentally determined. Both the fast isotopic equilibrium of glycolytic metabolite pools and the slow labeling dynamics of TCA cycle intermediates are described well by the model. The large pools of glutamate and aspartate which are linked to the TCA cycle via reversible aminotransferase reactions are likely to be responsible for the observed delay in equilibration of TCA cycle intermediates. Furthermore, it was estimated that 11% of the glucose taken up by astrocytes was diverted to the pentose phosphate pathway. In addition, considerable fluxes through pyruvate carboxylase [PC; PC/pyruvate dehydrogenase (PDH) ratio = 0.5], malic enzyme (5% of the total pyruvate production), and catabolism of branched-chained amino acids (contributing with ∼40% to total acetyl-CoA produced) confirmed the significance of these pathways to astrocytic metabolism. Consistent with the need of maintaining cytosolic redox potential, the fluxes through the malate–aspartate shuttle and the PDH pathway were comparable. Finally, the estimated glutamate/α-ketoglutarate exchange rate (∼0.7 μmol mg prot−1 h−1) was similar to the TCA cycle flux. In conclusion, this work demonstrates the potential of

  11. Metabolic gene profile in early human fetal heart development.

    PubMed

    Iruretagoyena, J I; Davis, W; Bird, C; Olsen, J; Radue, R; Teo Broman, A; Kendziorski, C; Splinter BonDurant, S; Golos, T; Bird, I; Shah, D

    2014-07-01

    The primitive cardiac tube starts beating 6-8 weeks post fertilization in the developing embryo. In order to describe normal cardiac development during late first and early second trimester in human fetuses this study used microarray and pathways analysis and created a corresponding 'normal' database. Fourteen fetal hearts from human fetuses between 10 and 18 weeks of gestational age (GA) were prospectively collected at the time of elective termination of pregnancy. RNA from recovered tissues was used for transcriptome analysis with Affymetrix 1.0 ST microarray chip. From the amassed data we investigated differences in cardiac development within the 10-18 GA period dividing the sample by GA in three groups: 10-12 (H1), 13-15 (H2) and 16-18 (H3) weeks. A fold change of 2 or above adjusted for a false discovery rate of 5% was used as initial cutoff to determine differential gene expression for individual genes. Test for enrichment to identify functional groups was carried out using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Array analysis correctly identified the cardiac specific genes, and transcripts reported to be differentially expressed were confirmed by qRT-PCR. Single transcript and Ontology analysis showed first trimester heart expression of myosin-related genes to be up-regulated >5-fold compared with second trimester heart. In contrast the second trimester hearts showed further gestation-related increases in many genes involved in energy production and cardiac remodeling. In conclusion, fetal heart development during the first trimester was dominated by heart-specific genes coding for myocardial development and differentiation. During the second trimester, transcripts related to energy generation and cardiomyocyte communication for contractile coordination/proliferation were more dominant. Transcripts related to fatty acid metabolism can be seen as early as 10 weeks and clearly increase as the heart matures. Retinol

  12. Metabolic profiles in five high-producing Swedish dairy herds with a history of abomasal displacement and ketosis

    PubMed Central

    Stengärde, Lena; Tråvén, Madeleine; Emanuelson, Ulf; Holtenius, Kjell; Hultgren, Jan; Niskanen, Rauni

    2008-01-01

    Background Body condition score and blood profiles have been used to monitor management and herd health in dairy cows. The aim of this study was to examine BCS and extended metabolic profiles, reflecting both energy metabolism and liver status around calving in high-producing herds with a high incidence of abomasal displacement and ketosis and to evaluate if such profiles can be used at herd level to pinpoint specific herd problems. Methods Body condition score and metabolic profiles around calving in five high-producing herds with high incidences of abomasal displacement and ketosis were assessed using linear mixed models (94 cows, 326 examinations). Cows were examined and blood sampled every three weeks from four weeks ante partum (ap) to nine weeks postpartum (pp). Blood parameters studied were glucose, fructosamine, non-esterified fatty acids (NEFA), insulin, β-hydroxybutyrate, aspartate aminotransferase, glutamate dehydrogenase, haptoglobin and cholesterol. Results All herds had overconditioned dry cows that lost body condition substantially the first 4–6 weeks pp. Two herds had elevated levels of NEFA ap and three herds had elevated levels pp. One herd had low levels of insulin ap and low levels of cholesterol pp. Haptoglobin was detected pp in all herds and its usefulness is discussed. Conclusion NEFA was the parameter that most closely reflected the body condition losses while these losses were not seen in glucose and fructosamine levels. Insulin and cholesterol were potentially useful in herd profiles but need further investigation. Increased glutamate dehydrogenase suggested liver cell damage in all herds. PMID:18687108

  13. Method and apparatus for measuring irradiated fuel profiles

    DOEpatents

    Lee, David M.

    1982-01-01

    A new apparatus is used to substantially instantaneously obtain a profile of an object, for example a spent fuel assembly, which profile (when normalized) has unexpectedly been found to be substantially identical to the normalized profile of the burnup monitor Cs-137 obtained with a germanium detector. That profile can be used without normalization in a new method of identifying and monitoring in order to determine for example whether any of the fuel has been removed. Alternatively, two other new methods involve calibrating that profile so as to obtain a determination of fuel burnup (which is important for complying with safeguards requirements, for utilizing fuel to an optimal extent, and for storing spent fuel in a minimal amount of space). Using either of these two methods of determining burnup, one can reduce the required measurement time significantly (by more than an order of magnitude) over existing methods, yet retain equal or only slightly reduced accuracy.

  14. A novel platform for automated high-throughput fluxome profiling of metabolic variants.

    PubMed

    Heux, Stéphanie; Poinot, Juliette; Massou, Stéphane; Sokol, Serguei; Portais, Jean-Charles

    2014-09-01

    Advances in metabolic engineering are enabling the creation of a large number of cell factories. However, high-throughput platforms do not yet exist for rapidly analyzing the metabolic network of the engineered cells. To fill the gap, we developed an integrated solution for fluxome profiling of large sets of biological systems and conditions. This platform combines a robotic system for (13)C-labelling experiments and sampling of labelled material with NMR-based isotopic fingerprinting and automated data interpretation. As a proof-of-concept, this workflow was applied to discriminate between Escherichia coli mutants with gradual expression of the glucose-6-phosphate dehydrogenase. Metabolic variants were clearly discriminated while pathways that support metabolic flexibility towards modulation of a single enzyme were elucidating. By directly connecting the data flow between cell cultivation and flux quantification, considerable advances in throughput, robustness, release of resources and screening capacity were achieved. This will undoubtedly facilitate the development of efficient cell factories.

  15. Adaptive method for electron bunch profile prediction

    NASA Astrophysics Data System (ADS)

    Scheinker, Alexander; Gessner, Spencer

    2015-10-01

    We report on an experiment performed at the Facility for Advanced Accelerator Experimental Tests (FACET) at SLAC National Accelerator Laboratory, in which a new adaptive control algorithm, one with known, bounded update rates, despite operating on analytically unknown cost functions, was utilized in order to provide quasi-real-time bunch property estimates of the electron beam. Multiple parameters, such as arbitrary rf phase settings and other time-varying accelerator properties, were simultaneously tuned in order to match a simulated bunch energy spectrum with a measured energy spectrum. The simple adaptive scheme was digitally implemented using matlab and the experimental physics and industrial control system. The main result is a nonintrusive, nondestructive, real-time diagnostic scheme for prediction of bunch profiles, as well as other beam parameters, the precise control of which are important for the plasma wakefield acceleration experiments being explored at FACET.

  16. Adaptive method for electron bunch profile prediction

    SciTech Connect

    Scheinker, Alexander; Gessner, Spencer

    2015-10-01

    We report on an experiment performed at the Facility for Advanced Accelerator Experimental Tests (FACET) at SLAC National Accelerator Laboratory, in which a new adaptive control algorithm, one with known, bounded update rates, despite operating on analytically unknown cost functions, was utilized in order to provide quasi-real-time bunch property estimates of the electron beam. Multiple parameters, such as arbitrary rf phase settings and other time-varying accelerator properties, were simultaneously tuned in order to match a simulated bunch energy spectrum with a measured energy spectrum. The simple adaptive scheme was digitally implemented using matlab and the experimental physics and industrial control system. The main result is a nonintrusive, nondestructive, real-time diagnostic scheme for prediction of bunch profiles, as well as other beam parameters, the precise control of which are important for the plasma wakefield acceleration experiments being explored at FACET. © 2015 authors. Published by the American Physical Society.

  17. Adaptive method for electron bunch profile prediction

    DOE PAGES

    Scheinker, Alexander; Gessner, Spencer

    2015-10-15

    We report on an experiment performed at the Facility for Advanced Accelerator Experimental Tests (FACET) at SLAC National Accelerator Laboratory, in which a new adaptive control algorithm, one with known, bounded update rates, despite operating on analytically unknown cost functions, was utilized in order to provide quasi-real-time bunch property estimates of the electron beam. Multiple parameters, such as arbitrary rf phase settings and other time-varying accelerator properties, were simultaneously tuned in order to match a simulated bunch energy spectrum with a measured energy spectrum. Thus, the simple adaptive scheme was digitally implemented using matlab and the experimental physics and industrialmore » control system. Finally, the main result is a nonintrusive, nondestructive, real-time diagnostic scheme for prediction of bunch profiles, as well as other beam parameters, the precise control of which are important for the plasma wakefield acceleration experiments being explored at FACET.« less

  18. Metabolic profiles of sunflower genotypes with contrasting response to Sclerotinia sclerotiorum infection.

    PubMed

    Peluffo, Lucila; Lia, Verónica; Troglia, Carolina; Maringolo, Carla; Norma, Paniego; Escande, Alberto; Esteban Hopp, H; Lytovchenko, Anna; Fernie, Alisdair R; Heinz, Ruth; Carrari, Fernando

    2010-01-01

    We report a comprehensive primary metabolite profiling of sunflower (Helianthus annuus) genotypes displaying contrasting behavior to Sclerotinia sclerotiorum infection. Applying a GC-MS-based metabolite profiling approach, we were able to identify differential patterns involving a total of 63 metabolites including major and minor sugars and sugar alcohols, organic acids, amino acids, fatty acids and few soluble secondary metabolites in the sunflower capitulum, the main target organ of pathogen attack. Metabolic changes and disease incidence of the two contrasting genotypes were determined throughout the main infection period (R5.2-R6). Both point-by-point and non-parametric statistical analyses showed metabolic differences between genotypes as well as interaction effects between genotype and time after inoculation. Network correlation analyses suggested that these metabolic changes were synchronized in a time-dependent manner in response to the pathogen. Concerted differential metabolic changes were detected to a higher extent in the susceptible, rather than the resistant genotype, thereby allowing differentiation of modules composed by intermediates of the same pathway which are highly interconnected in the susceptible line but not in the resistant one. Evaluation of these data also demonstrated a genotype specific regulation of distinct metabolic pathways, suggesting the importance of detection of metabolic patterns rather than specific metabolite changes when looking for metabolic markers differentially responding to pathogen infection. In summary, the GC-MS strategy developed in this study was suitable for detection of differences in carbon primary metabolism in sunflower capitulum, a tissue which is the main entry point for this and other pathogens which cause great detrimental impact on crop yield.

  19. Metabolic-flux profiling of the yeasts Saccharomyces cerevisiae and Pichia stipitis.

    PubMed

    Fiaux, Jocelyne; Cakar, Z Petek; Sonderegger, Marco; Wüthrich, Kurt; Szyperski, Thomas; Sauer, Uwe

    2003-02-01

    The so far largely uncharacterized central carbon metabolism of the yeast Pichia stipitis was explored in batch and glucose-limited chemostat cultures using metabolic-flux ratio analysis by nuclear magnetic resonance. The concomitantly characterized network of active metabolic pathways was compared to those identified in Saccharomyces cerevisiae, which led to the following conclusions. (i) There is a remarkably low use of the non-oxidative pentose phosphate (PP) pathway for glucose catabolism in S. cerevisiae when compared to P. stipitis batch cultures. (ii) Metabolism of P. stipitis batch cultures is fully respirative, which contrasts with the predominantly respiro-fermentative metabolic state of S. cerevisiae. (iii) Glucose catabolism in chemostat cultures of both yeasts is primarily oxidative. (iv) In both yeasts there is significant in vivo malic enzyme activity during growth on glucose. (v) The amino acid biosynthesis pathways are identical in both yeasts. The present investigation thus demonstrates the power of metabolic-flux ratio analysis for comparative profiling of central carbon metabolism in lower eukaryotes. Although not used for glucose catabolism in batch culture, we demonstrate that the PP pathway in S. cerevisiae has a generally high catabolic capacity by overexpressing the Escherichia coli transhydrogenase UdhA in phosphoglucose isomerase-deficient S. cerevisiae.

  20. Intervention of pumpkin seed oil on metabolic disease revealed by metabonomics and transcript profile.

    PubMed

    Zhao, Xiu-Ju; Chen, Yu-Lian; Fu, Bing; Zhang, Wen; Liu, Zhiguo; Zhuo, Hexian

    2017-03-01

    Understanding the metabolic and transcription basis of pumpkin seed oil (PSO) intervention on metabolic disease (MD) is essential to daily nutrition and health. This study analyzed the liver metabolic variations of Wistar rats fed normal diet (CON), high-fat diet (HFD) and high-fat plus PSO diet (PSO) to establish the relationship between the liver metabolite composition/transcript profile and the effects of PSO on MD. By using proton nuclear magnetic resonance spectroscopy together with multivariate data analysis, it was found that, compared with CON rats, HFD rats showed clear dysfunctions of choline metabolism, glucose metabolism and nucleotide and amino acid metabolism. Using quantitative real-time polymerase chain reaction (qPCR), it was found that, compared with HFD rats, PSO rats showed alleviated endoplasmic reticulum stress accompanied by lowered unfolded protein response. These findings provide useful information to understand the metabolic alterations triggered by MD and to evaluate the effects of PSO intervention. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  1. Solid phase extraction and metabolic profiling of exudates from living copepods.

    PubMed

    Selander, Erik; Heuschele, Jan; Nylund, Göran M; Pohnert, Georg; Pavia, Henrik; Bjærke, Oda; Pender-Healy, Larisa A; Tiselius, Peter; Kiørboe, Thomas

    2016-01-01

    Copepods are ubiquitous in aquatic habitats. They exude bioactive compounds that mediate mate finding or induce defensive traits in prey organisms. However, little is known about the chemical nature of the copepod exometabolome that contributes to the chemical landscape in pelagic habitats. Here we describe the development of a closed loop solid phase extraction setup that allows for extraction of exuded metabolites from live copepods. We captured exudates from male and female Temora longicornis and analyzed the content with high resolution LC-MS. Chemometric methods revealed 87 compounds that constitute a specific chemical pattern either qualitatively or quantitatively indicating copepod presence. The majority of the compounds were present in both female and male exudates, but nine compounds were mainly or exclusively present in female exudates and hence potential pheromone candidates. Copepodamide G, known to induce defensive responses in phytoplankton, was among the ten compounds of highest relative abundance in both male and female extracts. The presence of copepodamide G shows that the method can be used to capture and analyze chemical signals from living source organisms. We conclude that solid phase extraction in combination with metabolic profiling of exudates is a useful tool to develop our understanding of the chemical interplay between pelagic organisms.

  2. Solid phase extraction and metabolic profiling of exudates from living copepods

    PubMed Central

    Heuschele, Jan; Nylund, Göran M.; Pohnert, Georg; Pavia, Henrik; Bjærke, Oda; Pender-Healy, Larisa A.; Tiselius, Peter; Kiørboe, Thomas

    2016-01-01

    Copepods are ubiquitous in aquatic habitats. They exude bioactive compounds that mediate mate finding or induce defensive traits in prey organisms. However, little is known about the chemical nature of the copepod exometabolome that contributes to the chemical landscape in pelagic habitats. Here we describe the development of a closed loop solid phase extraction setup that allows for extraction of exuded metabolites from live copepods. We captured exudates from male and female Temora longicornis and analyzed the content with high resolution LC-MS. Chemometric methods revealed 87 compounds that constitute a specific chemical pattern either qualitatively or quantitatively indicating copepod presence. The majority of the compounds were present in both female and male exudates, but nine compounds were mainly or exclusively present in female exudates and hence potential pheromone candidates. Copepodamide G, known to induce defensive responses in phytoplankton, was among the ten compounds of highest relative abundance in both male and female extracts. The presence of copepodamide G shows that the method can be used to capture and analyze chemical signals from living source organisms. We conclude that solid phase extraction in combination with metabolic profiling of exudates is a useful tool to develop our understanding of the chemical interplay between pelagic organisms. PMID:26788422

  3. Microarray Analysis of the Gene Expression Profile and Lipid Metabolism in Fat-1 Transgenic Cattle.

    PubMed

    Liu, Xinfeng; Bai, Chunling; Ding, Xiangbin; Wei, Zhuying; Guo, Hong; Li, Guangpeng

    2015-01-01

    Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are beneficial for human health. However, humans and mammals are unable to synthesize n-3 PUFAs because they lack the n-3 desaturase gene fat-1 and must therefore obtain this type of fatty acid through their diet. Through the production of fat-1 transgenic animals, it is possible to obtain animal products that are rich in n-3 PUFAs, such as meat and milk. The aim of this study was to analyze the gene expression profile and the mechanism of lipid metabolism in fat-1 transgenic cattle and to accumulate important basic data that are required to obtain more efficient fat-1 transgenic cattle. Transcriptome profiling of fat-1 transgenic and wild-type cattle identified differentially expressed genes that are involved in 90 biological pathways, eight pathways of which were related to lipid metabolism processes 36 genes of which were related to lipid metabolism. This analysis also identified 11 significantly enriched genes that were involved in the peroxisome proliferator-activated receptor signaling pathway. These findings were verified by quantitative polymerase chain reaction. The information obtained in this study indicated that the introduction of an exogenous fat-1 gene into cattle affects the gene expression profile and the process of lipid metabolism in these animals. These results may provide important insights into how an exogenous fat-1 gene synthesizes n-3 PUFAs in transgenic cattle and other mammals.

  4. Bromochloromethane, a Methane Analogue, Affects the Microbiota and Metabolic Profiles of the Rat Gastrointestinal Tract

    PubMed Central

    Yang, Yu-Xiang; Mu, Chun-Long; Luo, Zhen

    2015-01-01

    Bromochloromethane (BCM), an inhibitor of methanogenesis, has been used in animal production. However, little is known about its impact on the intestinal microbiota and metabolic patterns. The present study aimed to investigate the effect of BCM on the colonic bacterial community and metabolism by establishing a Wistar rat model. Twenty male Wistar rats were randomly divided into two groups (control and treated with BCM) and raised for 6 weeks. Bacterial fermentation products in the cecum were determined, and colonic methanogens and sulfate-reducing bacteria (SRB) were quantified. The colonic microbiota was analyzed by pyrosequencing of the 16S rRNA genes, and metabolites were profiled by gas chromatography and mass spectrometry. The results showed that BCM did not affect body weight and feed intake, but it did significantly change the intestinal metabolic profiles. Cecal protein fermentation was enhanced by BCM, as methylamine, putrescine, phenylethylamine, tyramine, and skatole were significantly increased. Colonic fatty acid and carbohydrate concentrations were significantly decreased, indicating the perturbation of lipid and carbohydrate metabolism by BCM. BCM treatment decreased the abundance of methanogen populations, while SRB were increased in the colon. BCM did not affect the total colonic bacterial counts but significantly altered the bacterial community composition by decreasing the abundance of actinobacteria, acidobacteria, and proteobacteria. The results demonstrated that BCM treatment significantly altered the microbiotic and metabolite profiles in the intestines, which may provide further information on the use of BCM in animal production. PMID:26567308

  5. Microarray Analysis of the Gene Expression Profile and Lipid Metabolism in Fat-1 Transgenic Cattle

    PubMed Central

    Liu, Xinfeng; Bai, Chunling; Ding, Xiangbin; Wei, Zhuying; Guo, Hong; Li, Guangpeng

    2015-01-01

    Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are beneficial for human health. However, humans and mammals are unable to synthesize n-3 PUFAs because they lack the n-3 desaturase gene fat-1 and must therefore obtain this type of fatty acid through their diet. Through the production of fat-1 transgenic animals, it is possible to obtain animal products that are rich in n-3 PUFAs, such as meat and milk. The aim of this study was to analyze the gene expression profile and the mechanism of lipid metabolism in fat-1 transgenic cattle and to accumulate important basic data that are required to obtain more efficient fat-1 transgenic cattle. Transcriptome profiling of fat-1 transgenic and wild-type cattle identified differentially expressed genes that are involved in 90 biological pathways, eight pathways of which were related to lipid metabolism processes 36 genes of which were related to lipid metabolism. This analysis also identified 11 significantly enriched genes that were involved in the peroxisome proliferator-activated receptor signaling pathway. These findings were verified by quantitative polymerase chain reaction. The information obtained in this study indicated that the introduction of an exogenous fat-1 gene into cattle affects the gene expression profile and the process of lipid metabolism in these animals. These results may provide important insights into how an exogenous fat-1 gene synthesizes n-3 PUFAs in transgenic cattle and other mammals. PMID:26426396

  6. Multi-Organ Contribution to the Metabolic Plasma Profile Using Hierarchical Modelling

    PubMed Central

    Torell, Frida; Bennett, Kate; Cereghini, Silvia; Rännar, Stefan; Lundstedt-Enkel, Katrin; Moritz, Thomas; Haumaitre, Cecile; Trygg, Johan; Lundstedt, Torbjörn

    2015-01-01

    Hierarchical modelling was applied in order to identify the organs that contribute to the levels of metabolites in plasma. Plasma and organ samples from gut, kidney, liver, muscle and pancreas were obtained from mice. The samples were analysed using gas chromatography time-of-flight mass spectrometry (GC TOF-MS) at the Swedish Metabolomics centre, Umeå University, Sweden. The multivariate analysis was performed by means of principal component analysis (PCA) and orthogonal projections to latent structures (OPLS). The main goal of this study was to investigate how each organ contributes to the metabolic plasma profile. This was performed using hierarchical modelling. Each organ was found to have a unique metabolic profile. The hierarchical modelling showed that the gut, kidney and liver demonstrated the greatest contribution to the metabolic pattern of plasma. For example, we found that metabolites were absorbed in the gut and transported to the plasma. The kidneys excrete branched chain amino acids (BCAAs) and fatty acids are transported in the plasma to the muscles and liver. Lactic acid was also found to be transported from the pancreas to plasma. The results indicated that hierarchical modelling can be utilized to identify the organ contribution of unknown metabolites to the metabolic profile of plasma. PMID:26086868

  7. MELANCHOLIC DEPRESSION PREDICTION BY IDENTIFYING REPRESENTATIVE FEATURES IN METABOLIC AND MICROARRAY PROFILES WITH MISSING VALUES

    PubMed Central

    Nie, Zhi; Yang, Tao; Liu, Yashu; Lin, Binbin; Li, Qingyang; Narayan, Vaibhav A; Wittenberg, Gayle; Ye, Jieping

    2014-01-01

    Recent studies have revealed that melancholic depression, one major subtype of depression, is closely associated with the concentration of some metabolites and biological functions of certain genes and pathways. Meanwhile, recent advances in biotechnologies have allowed us to collect a large amount of genomic data, e.g., metabolites and microarray gene expression. With such a huge amount of information available, one approach that can give us new insights into the understanding of the fundamental biology underlying melancholic depression is to build disease status prediction models using classification or regression methods. However, the existence of strong empirical correlations, e.g., those exhibited by genes sharing the same biological pathway in microarray profiles, tremendously limits the performance of these methods. Furthermore, the occurrence of missing values which are ubiquitous in biomedical applications further complicates the problem. In this paper, we hypothesize that the problem of missing values might in some way benefit from the correlation between the variables and propose a method to learn a compressed set of representative features through an adapted version of sparse coding which is capable of identifying correlated variables and addressing the issue of missing values simultaneously. An efficient algorithm is also developed to solve the proposed formulation. We apply the proposed method on metabolic and microarray profiles collected from a group of subjects consisting of both patients with melancholic depression and healthy controls. Results show that the proposed method can not only produce meaningful clusters of variables but also generate a set of representative features that achieve superior classification performance over those generated by traditional clustering and data imputation techniques. In particular, on both datasets, we found that in comparison with the competing algorithms, the representative features learned by the proposed

  8. Melancholic depression prediction by identifying representative features in metabolic and microarray profiles with missing values.

    PubMed

    Nie, Zhi; Yang, Tao; Liu, Yashu; Li, Qingyang; Narayan, Vaibhav A; Wittenberg, Gayle; Ye, Jieping

    2015-01-01

    Recent studies have revealed that melancholic depression, one major subtype of depression, is closely associated with the concentration of some metabolites and biological functions of certain genes and pathways. Meanwhile, recent advances in biotechnologies have allowed us to collect a large amount of genomic data, e.g., metabolites and microarray gene expression. With such a huge amount of information available, one approach that can give us new insights into the understanding of the fundamental biology underlying melancholic depression is to build disease status prediction models using classification or regression methods. However, the existence of strong empirical correlations, e.g., those exhibited by genes sharing the same biological pathway in microarray profiles, tremendously limits the performance of these methods. Furthermore, the occurrence of missing values which are ubiquitous in biomedical applications further complicates the problem. In this paper, we hypothesize that the problem of missing values might in some way benefit from the correlation between the variables and propose a method to learn a compressed set of representative features through an adapted version of sparse coding which is capable of identifying correlated variables and addressing the issue of missing values simultaneously. An efficient algorithm is also developed to solve the proposed formulation. We apply the proposed method on metabolic and microarray profiles collected from a group of subjects consisting of both patients with melancholic depression and healthy controls. Results show that the proposed method can not only produce meaningful clusters of variables but also generate a set of representative features that achieve superior classification performance over those generated by traditional clustering and data imputation techniques. In particular, on both datasets, we found that in comparison with the competing algorithms, the representative features learned by the proposed

  9. Metabolic profile biomarkers of metal contamination in a sentinel terrestrial species are applicable across multiple sites.

    PubMed

    Bundy, Jacob G; Keun, Hector C; Sidhu, Jasmin K; Spurgeon, David J; Svendsen, Claus; Kille, Peter; Morgan, A John

    2007-06-15

    In this study, we addressed the question of whether an omic approach could genuinely be useful for biomarker profile analysis across different field sites with different physicochemical characteristics. We collected earthworms (Lumbricus rubellus) from seven sites with very different levels of metal contamination and prevailing soil type and analyzed tissue extracts by 1H nuclear magnetic resonance spectroscopy. Pattern recognition analysis of the data showed that both site- and contaminant-specific effects on the metabolic profiles could be discerned. Zinc was identified as the probable major contaminant causing a metabolic change in the earthworms. Individual sites could be resolved on the basis of NMR spectral profiles by principal component analysis; these site differences may also have been caused by additional abiotic factors such as soil pH. Despite an inevitable degree of confounding between site and contaminant concentrations, it was possible to identify metabolites which were correlated with zinc across all different sites. This study therefore acts as a proof of principle for the use of NMR-based metabolic profiling as a diagnostic tool for ecotoxicological research in polluted field soils.

  10. Behavioral extremes of trait anxiety in mice are characterized by distinct metabolic profiles.

    PubMed

    Filiou, Michaela D; Asara, John M; Nussbaumer, Markus; Teplytska, Larysa; Landgraf, Rainer; Turck, Christoph W

    2014-11-01

    No comprehensive metabolic profile of trait anxiety is to date available. To identify metabolic biosignatures for different anxiety states, we compared mice selectively inbred for ∼ 40 generations for high (HAB), normal (NAB) or low (LAB) anxiety-related behavior. Using a mass spectrometry-based targeted metabolomics approach, we quantified the levels of 257 unique metabolites in the cingulate cortex and plasma of HAB, NAB and LAB mice. We then pinpointed affected molecular systems in anxiety-related behavior by an in silico pathway and network prediction analysis followed by validation of in silico predicted alterations with molecular assays. We found distinct metabolic profiles for different trait anxiety states and detected metabolites with altered levels both in cingulate cortex and plasma. Metabolomics data revealed common candidate biomarkers in cingulate cortex and plasma for anxiety traits and in silico pathway analysis implicated amino acid metabolism, pyruvate metabolism, oxidative stress and apoptosis in the regulation of anxiety-related behavior. We report characteristic biosignatures for trait anxiety states and provide a network map of pathways involved in anxiety-related behavior. Pharmacological targeting of these pathways will enable a mechanism-based approach for identifying novel therapeutic targets for anxiety disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Dynamic metabolome profiling reveals significant metabolic changes during grain development of bread wheat (Triticum aestivum L.).

    PubMed

    Zhen, Shoumin; Dong, Kun; Deng, Xiong; Zhou, Jiaxing; Xu, Xuexin; Han, Caixia; Zhang, Wenying; Xu, Yanhao; Wang, Zhimin; Yan, Yueming

    2016-08-01

    Metabolites in wheat grains greatly influence nutritional values. Wheat provides proteins, minerals, B-group vitamins and dietary fiber to humans. These metabolites are important to human health. However, the metabolome of the grain during the development of bread wheat has not been studied so far. In this work the first dynamic metabolome of the developing grain of the elite Chinese bread wheat cultivar Zhongmai 175 was analyzed, using non-targeted gas chromatography/mass spectrometry (GC/MS) for metabolite profiling. In total, 74 metabolites were identified over the grain developmental stages. Metabolite-metabolite correlation analysis revealed that the metabolism of amino acids, carbohydrates, organic acids, amines and lipids was interrelated. An integrated metabolic map revealed a distinct regulatory profile. The results provide information that can be used by metabolic engineers and molecular breeders to improve wheat grain quality. The present metabolome approach identified dynamic changes in metabolite levels, and correlations among such levels, in developing seeds. The comprehensive metabolic map may be useful when breeding programs seek to improve grain quality. The work highlights the utility of GC/MS-based metabolomics, in conjunction with univariate and multivariate data analysis, when it is sought to understand metabolic changes in developing seeds. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  12. Comparing the impact of ultrafine particles from petrodiesel and biodiesel combustion to bacterial metabolism by targeted HPLC-MS/MS metabolic profiling.

    PubMed

    Zhong, Fanyi; Xu, Mengyang; Schelli, Katie; Rutowski, Joshua; Holmén, Britt A; Zhu, Jiangjiang

    2017-08-01

    Alterations of gut bacterial metabolism play an important role in their host metabolism, and can result in diseases such as obesity and diabetes. While many factors were discovered influencing the gut bacterial metabolism, exposure to ultrafine particles (UFPs) from engine combustions were recently proposed to be a potential risk factor for the perturbation of gut bacterial metabolism, and consequentially to obesity and diabetes development. This study focused on evaluation of how UFPs from diesel engine combustions impact gut bacterial metabolism. We hypothesize that UFPs from different type of diesel (petrodiesel vs. biodiesel) will both impact bacterial metabolism, and the degree of impact is also diesel type-dependent. Targeted metabolic profiling of 221 metabolites were applied to three model gut bacteria in vitro, Streptococcus salivarius, Lactobacillus acidophilus and Lactobacillus fermentum. UFPs from two types of fuels, petrodiesel (B0) and a biodiesel blend (B20: 20% soy biodiesel/80% B0 by volume), were exposed to the bacteria and their metabolic changes were compared. For each bacterial strain, metabolites with significantly changed abundance were observed in both perturbations, and all three strains have increased number of altered metabolites detected from B20 UFPs perturbation in comparison to B0 UFPs. Multivariate statistical analysis further confirmed that the metabolic profiles were clearly different between testing groups. Metabolic pathway analyses also demonstrated several important metabolic pathways, including pathways involves amino acids biosynthesis and sugar metabolism, were significantly impacted by UFPs exposure. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Metabolic profiling reveals that PNPLA3 induces widespread effects on metabolism beyond triacylglycerol remodeling in Huh-7 hepatoma cells

    PubMed Central

    Min, Hae-Ki; Sookoian, Silvia; Pirola, Carlos J.; Cheng, Jianfeng; Mirshahi, Faridoddin

    2014-01-01

    PNPLA3 was recently associated with the susceptibility to nonalcoholic fatty liver disease, a common cause of chronic liver disease characterized by abnormal triglyceride accumulation. Although it is established that PNPLA3 has both triacylglycerol lipase and acylglycerol O-acyltransferase activities, is still unknown whether the gene has any additional role in the modulation of the human liver metabolome. To uncover the functional role of PNPLA3 on liver metabolism, we performed high-throughput metabolic profiling of PNPLA3 siRNA-silencing and overexpression of wild-type and mutant Ile148Met variants (isoleucine/methionine substitution at codon 148) in Huh-7 cells. Metabolomic analysis was performed by using GC/MS and LC/MS platforms. Silencing of PNPLA3 was associated with a global perturbation of Huh-7 hepatoma cells that resembled a catabolic response associated with protein breakdown. A significant decrease in amino- and γ-glutamyl-amino acids and dipeptides and a significant increase in cysteine sulfinic acid, myo-inositol, lysolipids, sphingolipids, and polyunsaturated fatty acids were observed. Overexpression of the PNPLA3 Met148 variant mirrored many of the metabolic changes observed during gene silencing, but in the opposite direction. These findings were replicated by the exploration of canonical pathways associated with PNPLA3 silencing and Met148 overexpression. Overexpression of the PNPLA3 Met148 variant was associated with a 1.75-fold increase in lactic acid, suggesting a shift to anaerobic metabolism and mitochondrial dysfunction. Together, these results suggest a critical role of PNPLA3 in the modulation of liver metabolism beyond its classical participation in triacylglycerol remodeling. PMID:24763554

  14. Mass-spectra-based peak alignment for automatic nontargeted metabolic profiling analysis for biomarker screening in plant samples.

    PubMed

    Fu, Hai-Yan; Hu, Ou; Zhang, Yue-Ming; Zhang, Li; Song, Jing-Jing; Lu, Peang; Zheng, Qing-Xia; Liu, Ping-Ping; Chen, Qian-Si; Wang, Bing; Wang, Xiao-Yu; Han, Lu; Yu, Yong-Jie

    2017-09-01

    Nontargeted metabolic profiling analysis is a difficult task in a routine investigation because hundreds of chromatographic peaks are eluted within a short time, and the time shift problem is severe across samples. To address these problems, the present work developed an automatic nontargeted metabolic profiling analysis (anTMPA) method. First, peaks from the total ion chromatogram were extracted using modified multiscale Gaussian smoothing method. Then, a novel peak alignment strategy was employed based on the mass spectra and retention times of the peaks in which the maximum mass spectral correlation coefficient path was extracted using a modified dynamic programming method. Moreover, an automatic landmark peak-searching strategy was employed for self-adapting time shift modification. Missing peaks across samples were grouped and registered into the aligned peak list table for final refinement. Finally, the aligned peaks across samples were analyzed using statistical methods to identify potential biomarkers. Mass spectral information on the screened biomarkers could be directly imported into the National Institute of Standards and Technology library to select the candidate compounds. The performance of the anTMPA method was evaluated using a complicated plant gas chromatography-mass spectrometry dataset with the aim of identifying biomarkers between the growth and maturation stages of the tested plant. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Effects of ACE Inhibitors on Insulin Resistance and Lipid Profile in Children with Metabolic Syndrome

    PubMed Central

    Çelebi Bitkin, Eda; Boyraz, Mehmet; Taşkın, Necati; Akçay, Arzu; Ulucan, Korkut; Akyol, Mehmet Bedir; Akçay, Teoman

    2013-01-01

    Objective: The aim of this study was to evaluate the effects of using ACE inhibitors on insulin resistance, glucose metabolism, body fat composition, and lipid profile in children over 10 years of age with obesity-associated metabolic syndrome (MS). Methods: A total of 53 children with MS, who had been followed for at least one year were included in the study. The sample was divided into two groups: Group 1-30 obese children (13 female, 17 male) who were not using an ACE inhibitor and Group 2-23 obese children (13 female, 10 male) who were using an ACE inhibitor. Anthropometric and laboratory dataobtained at baseline and at the 3rd, 6th, and 12th months of follow-up were compared in the two groups. Results: Comparison of the data in the two groups at 3rd, 6th, and 12th months revealed no statistically significant differences in terms of weight standard deviation score (SDS), body mass index SDS, weight for height percentile, body fat percentage, and very low-density lipoprotein (VLDL)values. However, there were statistically significant differences in mean glucose and insulin levels, homeostasis model assessment for insulin resistance, LDL and high-density lipoprotein values, and highly significant differences in mean triglyceride values. Conclusions: The positive effects of ACE inhibitor drugs, particularly on hypertriglyceridemia and insulin resistance, might bring them forth as first-line drugs in the treatment of obese and hypertensive children. Randomized, controlled, double-blind, and long-term studies are needed for a definitive conclusion. Conflict of interest:None declared. PMID:24072084

  16. Metabolic Profiling of Somatic Tissues from Monochamus alternatus (Coleoptera: Cerambycidae) Reveals Effects of Irradiation on Metabolism

    PubMed Central

    Qu, Liangjian; Wang, Lijuan; Wang, Qinghua; Wang, Yuzhu; Zhang, Yongan

    2014-01-01

    A high-level of sexual sterility is of importance for the sterile insect technique (SIT). However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest. PMID:24937685

  17. Metabolic profiling of somatic tissues from Monochamus alternatus (Coleoptera: Cerambycidae) reveals effects of irradiation on metabolism.

    PubMed

    Qu, Liangjian; Wang, Lijuan; Wang, Qinghua; Wang, Yuzhu; Zhang, Yongan

    2014-06-16

    A high-level of sexual sterility is of importance for the sterile insect technique (SIT). However, the use of high-dose-intensity gamma radiation to induce sterility has negative impacts not only on reproductive cells but also on somatic cells. In this study, we investigated the metabolite differences in somatic tissues between non-irradiated, 20-Gy-irradiated, and 40-Gy-irradiated male Monochamus alternatus, an important vector of the pathogenic nematode, Bursaphelenchus xylophilus, which kills Asian pines. The results showed that metabolite levels changed moderately in the 20-Gy samples but were markedly altered in the 40-Gy samples compared with the non-irradiated samples. Twenty-six and 53 metabolites were disturbed by 20-Gy and 40-Gy radiation, respectively. Thirty-six metabolites were found to be markedly altered in the 40-Gy samples but were not changed significantly in the 20-Gy samples. The comprehensive metabolomic disorders induced by 40-Gy radiation dysregulated six metabolic pathways involved in the life process. The findings presented in this manuscript will contribute to our knowledge of the characteristic metabolic changes associated with gamma-radiation-induced damage to somatic cells and will allow for better exploration of the SIT for the control of this target pest.

  18. Metabolic Profiling of Retrograde Pathway Transcription Factors Rtg1 and Rtg3 Knockout Yeast

    PubMed Central

    Hashim, Zanariah; Mukai, Yukio; Bamba, Takeshi; Fukusaki, Eiichiro

    2014-01-01

    Rtg1 and Rtg3 are two basic helix-loop-helix (bHLH) transcription factors found in yeast Saccharomyces cerevisiae that are involved in the regulation of the mitochondrial retrograde (RTG) pathway. Under RTG response, anaplerotic synthesis of citrate is activated, consequently maintaining the supply of important precursors necessary for amino acid and nucleotide synthesis. Although the roles of Rtg1 and Rtg3 in TCA and glyoxylate cycles have been extensively reported, the investigation of other metabolic pathways has been lacking. Characteristic dimer formation in bHLH proteins, which allows for combinatorial gene expression, and the link between RTG and other regulatory pathways suggest more complex metabolic signaling involved in Rtg1/Rtg3 regulation. In this study, using a metabolomics approach, we examined metabolic alteration following RTG1 and RTG3 deletion. We found that apart from TCA and glyoxylate cycles, which have been previously reported, polyamine biosynthesis and other amino acid metabolism were significantly altered in RTG-deficient strains. We revealed that metabolic alterations occurred at various metabolic sites and that these changes relate to different growth phases, but the difference can be detected even at the mid-exponential phase, when mitochondrial function is repressed. Moreover, the effect of metabolic rearrangements can be seen through the chronological lifespan (CLS) measurement, where we confirmed the role of the RTG pathway in extending the yeast lifespan. Through a comprehensive metabolic profiling, we were able to explore metabolic phenotypes previously unidentified by other means and illustrate the possible correlations of Rtg1 and Rtg3 in different pathways. PMID:25007314

  19. Fiber evanescent wave spectroscopy using the mid-infrared provides useful fingerprints for metabolic profiling in humans

    NASA Astrophysics Data System (ADS)

    Anne, Marie-Laure; Le Lan, Caroline; Monbet, Valérie; Boussard-Plédel, Catherine; Ropert, Martine; Sire, Olivier; Pouchard, Michel; Jard, Christine; Lucas, Jacques; Adam, Jean Luc; Brissot, Pierre; Bureau, Bruno; Loréal, Olivier

    2009-09-01

    Fiber evanescent wave spectroscopy (FEWS) explores the mid-infrared domain, providing information on functional chemical groups represented in the sample. Our goal is to evaluate whether spectral fingerprints obtained by FEWS might orientate clinical diagnosis. Serum samples from normal volunteers and from four groups of patients with metabolic abnormalities are analyzed by FEWS. These groups consist of iron overloaded genetic hemochromatosis (GH), iron depleted GH, cirrhosis, and dysmetabolic hepatosiderosis (DYSH). A partial least squares (PLS) logistic method is used in a training group to create a classification algorithm, thereafter applied to a test group. Patients with cirrhosis or DYSH, two groups exhibiting important metabolic disturbances, are clearly discriminated from control groups with AUROC values of 0.94+/-0.05 and 0.90+/-0.06, and sensibility/specificity of 86/84% and 87/87%, respectively. When pooling all groups, the PLS method contributes to discriminate controls, cirrhotic, and dysmetabolic patients. Our data demonstrate that metabolic profiling using infrared FEWS is a possible way to investigate metabolic alterations in patients.

  20. Method and apparatus for measuring irradiated fuel profiles

    DOEpatents

    Lee, D.M.

    1980-03-27

    A new apparatus is used to substantially instantaneously obtain a profile of an object, for example a spent fuel assembly, which profile (when normalized) has unexpectedly been found to be substantially identical to the normalized profile of the burnup monitor Cs-137 obtained with a germanium detector. That profile can be used without normalization in a new method of identifying and monitoring in order to determine for example whether any of the fuel has been removed. Alternatively, two other new methods involve calibrating that profile so as to obtain a determination of fuel burnup (which is important for complying with safeguards requirements, for utilizing fuel to an optimal extent, and for storing spent fuel in a minimal amount of space).

  1. Method for metabolizing carbazole in petroleum

    DOEpatents

    Kayser, Kevin J.; Kilbane, II, John J.

    2005-09-13

    A method for selective cleavage of C--N bonds genes that encode for at least one enzyme suitable for conversion of carbazole to 2-aminobiphenyl-2,3-diol are combined with a gene encoding an amidase suitable for selectively cleaving a C--N bond in 2-aminobiphenyl-2,3-diol, forming an operon that encodes for cleavage of both C--N bonds of said carbazole. The operon is inserted into a host culture which, in turn, is contacted with the carbazole, resulting in selective cleavage of both C--N bonds of the carbazole. Also disclosed is a new microorganism that expresses a carbazole degradation trait constitutively and a method for degrading carbazole employing this microorganism.

  2. Serum metabolic and minerals profile in norgestomet primed postpartum anestrous surti buffaloes

    PubMed Central

    Parmar, Sanjay C.; Khasatiya, C. T.; Chaudhary, J. K.; Patel, R. V.; Dhamsaniya, H. B.

    2015-01-01

    Aim: The study was undertaken to find out the serum metabolic and minerals profile in postpartum anestrous surti buffaloes treated with norgestomet ear implants alone and in combination with pregnant mare serum gonadotropin (PMSG). Materials and Methods: The study was conducted on 18 postpartum anestrous Surti buffaloes divided into three groups of six animals each at random to conduct the experiment. The buffaloes in Group-I and Group-II were implanted with Crestar ear implant for 9 days together with 2 ml injection of Crestar solution given i/m on the day of the implant insertion. In Group-II, additionally 500 IU PMSG was given i/m on the day of implant removal, whereas the buffaloes in Group-III served as anestrous control group and received 5 ml Normal Saline i/m on day 0 and 9 as a placebo treatment. Results: The overall serum total protein values did not differ significantly (p > 0.05) between time (days) intervals in any of the groups. The mean serum total cholesterol levels at 10th day and on the day of estrus were found significantly lower (p < 0.05) in the control group as compared to treatment Groups I and II. However, there was no significant difference (p > 0.05) at 10th day and on the day of estrus between treatment groups (T1 and T2). The overall mean serum cobalt, zinc, iron, and manganese values did not differ significantly (p > 0.05) between different time intervals among any of the groups, except copper which was significantly lower (p < 0.05) at 10th day in control group as compared to treatment groups. Conclusion: Microelements cannot be synthesized in the body. Hence, it is concluded that the mineral mixture should be supplied daily in the animals ration to suffice the requirement of the trace elements. The mean serum metabolic and micro-minerals profiles in treatment and control groups revealed that overall mean serum total protein, cholesterol, copper, and zinc levels were apparently higher in treatment groups whereas, mean serum cobalt

  3. Nuclear Magnetic Resonance (NMR) Spectroscopy For Metabolic Profiling of Medicinal Plants and Their Products.

    PubMed

    Kumar, Dinesh

    2016-09-02

    NMR spectroscopy has multidisciplinary applications, including excellent impact in metabolomics. The analytical capacity of NMR spectroscopy provides information for easy qualitative and quantitative assessment of both endogenous and exogenous metabolites present in biological samples. The complexity of a particular metabolite and its contribution in a biological system are critically important for understanding the functional state that governs the organism's phenotypes. This review covers historical aspects of developments in the NMR field, its applications in chemical profiling, metabolomics, and quality control of plants and their derived medicines, foods, and other products. The bottlenecks of NMR in metabolic profiling are also discussed, keeping in view the future scope and further technological interventions.

  4. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells

    PubMed Central

    Armitage, Emily G.; Kotze, Helen L.; Allwood, J. William; Dunn, Warwick B.; Goodacre, Royston; Williams, Kaye J.

    2015-01-01

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments. PMID:26508589

  5. Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells.

    PubMed

    Armitage, Emily G; Kotze, Helen L; Allwood, J William; Dunn, Warwick B; Goodacre, Royston; Williams, Kaye J

    2015-10-28

    Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments.

  6. Effect of long-distance transportation on serum metabolic profiles of steer calves.

    PubMed

    Takemoto, Satoshi; Tomonaga, Shozo; Funaba, Masayuki; Matsui, Tohru

    2017-07-19

    Long-distance transportation is sometimes inevitable in the beef industry because of the geographic separation of major breeding and fattening areas. Long-distance transportation negatively impacts production and health of cattle, which may, at least partly, result from the disturbance of metabolism during and after transportation. However, alteration of metabolism remains elusive in transported cattle. We investigated the effects of transportation on the metabolomic profiles of Holstein steer calves. Non-targeted analysis of serum concentrations of low molecular weight metabolites was performed by gas chromatography mass spectrometry. Transportation affected 38 metabolites in the serum. A pathway analysis suggested that 26, 10, and 10 pathways were affected immediately after transportation, and 3 and 7 days after transportation, respectively. Some pathways were disturbed only immediately after transportation, likely because of feed and water withdrawal during transit. Nicotinate and nicotinamide metabolism, and citric acid cycle were affected for 3 days after transportation, whereas propionate metabolism, phenylalanine and tyrosine metabolism were affected throughout the experiment. Four pathways were not affected immediately after transportation, but were altered thereafter. These results suggested that many metabolic pathways had marked perturbations during transportation. Metabolites such as citric acid, propionate, tyrosine and niacin can be candidate supplements for mitigating transportation-induced adverse effects. © 2017 Japanese Society of Animal Science.

  7. [Global expression profiling of Saccharomyces cerevisiae: metabolic remodeling in post-log phase].

    PubMed

    Ye, Yanrui; Tang, Yuqian; Chen, Hongyun; Zheng, Suiping; Pan, Li; Lin, Ying

    2008-06-01

    For the purpose of revealing the mechanism of the reduction of yeasts ethanol production rate after entrance of post-log phase, we used microarray to study expression profiles of the yeast Saccharomyces cerevisiae during the transition from mid-log growth phase to post-log growth. The results demonstrate that the global pattern of gene expression is very stable during the mid-log phase. However, a dramatic metabolic remodeling was found when the yeast entries post-log phase, during which many of amino acid synthesis and metabolism related genes are up-regulated, moreover, ion transport, energy generation and storage related genes are also up regulated during this phase, while a large number of genes involved in transposition and DNA recombination are repressed. Central metabolic pathways also engage in metabolic remodeling, within which the genes involved in succinate and a-ketoglutarate synthesis pathways are up regulated, accordance with those of amino acid synthesis and metabolism. These results demonstrate that the increasing demand for amino acids in post-log phase lead to a metabolic transition into TCA cycle and glyoxylate cycle, which subsequently reduce the ethanol production rate. This suggests a global insight into the process of yeast ethanol fermentation.

  8. Distribution of Metabolically Active Prokaryotes (Archaea and Bacteria) throughout the Profiles of Chernozem and Brown Semidesert Soil

    NASA Astrophysics Data System (ADS)

    Semenov, M. V.; Manucharova, N. A.; Stepanov, A. L.

    2016-02-01

    The distribution of metabolically active cells of archaea and bacteria in the profiles of typical chernozems (Voronezh oblast) and brown semidesert soils (Astrakhan oblast) of natural and agricultural ecosystems was studied using the method of fluorescent in situ hybridization (FISH). The studied soils differed sharply in the microbial biomass and in the numbers of metabolically active cells of archaea and bacteria. The number of active bacterial cells was 3.5-7.0 times greater than that of archaea. In the arable chernozem, the numbers of active cells of archaea and bacteria were 2.6 and 1.5 times, respectively, lower than those in the chernozem under the shelterbelt. The agricultural use of the brown semidesert soil had little effect on the abundances of bacteria and archaea. The soil organic carbon content was the major factor controlling the numbers of metabolically active cells of both domains. However, the dependence of the abundance of bacteria on the organic matter content was more pronounced. The decrease in the organic carbon and total nitrogen contents down the soil profiles was accompanied by the decrease in the bacteria: archaea ratio attesting to a better adaptation of archaea to the permanent deficiency of carbon and nitrogen. The bacteria: archaea ratio can serve as an ecotrophic indicator of the state of soil microbial communities.

  9. Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

    PubMed Central

    Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

    2013-01-01

    Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

  10. Metabolic profiling directly from the Petri dish using nanoDESI imaging mass spectrometry

    PubMed Central

    Watrous, Jeramie; Roach, Patrick; Heath, Brandi; Alexandrov, Theodore; Laskin, Julia; Dorrestein, Pieter C.

    2014-01-01

    Understanding molecular interaction pathways in complex biological systems constitutes a treasure trove of knowledge that might facilitate the specific, chemical manipulation of the countless microbiological systems that occur throughout our world. However, there is a lack of methodologies that allow the direct investigation of chemical gradients and interactions in living biological systems, in real time. Here we report the use of nanospray desorption electrospray ionization (nanoDESI) imaging mass spectrometry for in vivo metabolic profiling of living bacterial colonies directly from the Petri dish with absolutely no sample preparation needed. Using this technique, we investigated single colonies of Shewanella oneidensis MR-1, Bacillus subtilis 3610, Streptomyces coelicolor A3(2) as well as a mixed biofilm of S. oneidensis MR-1 and B. subtilis 3610. Data from B. subtilis 3610 and S. coelicolor A3(2) provided a means of validation for the method while data from S. oneidensis MR-1 and the mixed biofilm showed a wide range of compounds that this bacterium uses for the dissimilatory reduction of extracellular metal oxides, including riboflavin, iron-bound heme and heme biosynthetic intermediates, and the siderophore putrebactin. PMID:24047514

  11. Metabolic Profiling Directly from the Petri Dish Using Nanospray Desorption Electrospray Ionization Imaging Mass Spectrometry

    SciTech Connect

    Watrous, Jeramie D.; Roach, Patrick J.; Heath, Brandi S.; Alexandrov, Theodore; Laskin, Julia; Dorrestein, Pieter C.

    2013-11-05

    Understanding molecular interaction pathways in complex biological systems constitutes a treasure trove of knowledge that might facilitate the specific, chemical manipulation of the countless microbiological systems that occur throughout our world. However, there is a lack of methodologies that allow the direct investigation of chemical gradients and interactions in living biological systems, in real time. Here, we report the use of nanospray desorption electrospray ionization (nanoDESI) imaging mass spectrometry for in vivo metabolic profiling of living bacterial colonies directly from the Petri dish with absolutely no sample preparation needed. Using this technique, we investigated single colonies of Shewanella oneidensis MR-1, Bacillus subtilis 3610, and Streptomyces coelicolor A3(2) as well as a mixed biofilm of S. oneidensis MR-1 and B. subtilis 3610. Data from B. subtilis 3610 and S. coelicolor A3(2) provided a means of validation for the method while data from S. oneidensis MR-1 and the mixed biofilm showed a wide range of compounds that this bacterium uses for the dissimilatory reduction of extracellular metal oxides, including riboflavin, iron-bound heme and heme biosynthetic intermediates, and the siderophore putrebactin.

  12. The impact of body condition after calving on metabolism and milk progesterone profiles in two breeds of dairy cows.

    PubMed

    O'Hara, Lisa A; Båge, Renée; Holtenius, Kjell

    2016-10-20

    Optimal body condition in early lactation is generally accepted as a prerequisite for good reproductive performance. Examination of milk progesterone profiles offers an objective method for characterization of postpartum ovarian activity in dairy cows. The present study investigated the relationship between body condition after calving, some metabolic parameters in blood plasma, and fertility, as reflected by milk progesterone profiles in the two dairy breeds Swedish Red (SR) and Swedish Holstein (SH). Multiparous dairy cows (n = 73) of SR and SH breeds were selected and divided into three groups based on their body condition score (BCS) after parturition. Selected plasma metabolites were determined, milk progesterone profiles were identified and body condition was scored. Over-conditioned cows and atypical progesterone profiles were more common among SR cows. Insulin sensitivity was lower and IGF 1 higher among SR cows. Insulin was positively related to body condition, but not related to breed. Atypical progesterone profiles were more common and insulin sensitivity lower in SR than in SH cows, but the SR breed had a higher proportion of over-conditioned SR cows. It is reasonable to assume that breed differences in body condition contributed to these results.

  13. Gene Expression Profiles of Metabolic Aggressiveness and Tumor Recurrence in Benign Meningioma

    PubMed Central

    Serna, Eva; Morales, José Manuel; Mata, Manuel; Gonzalez-Darder, José; San Miguel, Teresa; Gil-Benso, Rosario; Lopez-Gines, Concha; Cerda-Nicolas, Miguel; Monleon, Daniel

    2013-01-01

    Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after surgery information for all of them. We measured gene expression by oligonucleotide microarray measurements on 19 of them. To our knowledge, this is the first time that distinct gene expression profiles are reported for benign meningioma molecular subgroups with clinical correlation. Our results show that metabolic aggressiveness in otherwise histological benign meningioma proceeds mostly through alterations in the expression of genes involved in the regulation of transcription, mainly the LMO3 gene. Genes involved in tumor metabolism, like IGF1R, are also differentially expressed in those meningioma subgroups with higher rates of membrane turnover, higher energy demand and increased resistance to apoptosis. These new subgroups of benign meningiomas exhibit different rates of recurrence. This work shows that benign meningioma with metabolic aggressiveness constitute a subgroup of potentially recurrent tumors in which alterations in genes regulating critical features of aggressiveness, like increased angiogenesis or cell invasion, are still no predominant. The determination of these gene expression biosignatures may allow the early detection of clinically aggressive tumors. PMID:23840654

  14. Gene expression profiles of metabolic aggressiveness and tumor recurrence in benign meningioma.

    PubMed

    Serna, Eva; Morales, José Manuel; Mata, Manuel; Gonzalez-Darder, José; San Miguel, Teresa; Gil-Benso, Rosario; Lopez-Gines, Concha; Cerda-Nicolas, Miguel; Monleon, Daniel

    2013-01-01

    Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after surgery information for all of them. We measured gene expression by oligonucleotide microarray measurements on 19 of them. To our knowledge, this is the first time that distinct gene expression profiles are reported for benign meningioma molecular subgroups with clinical correlation. Our results show that metabolic aggressiveness in otherwise histological benign meningioma proceeds mostly through alterations in the expression of genes involved in the regulation of transcription, mainly the LMO3 gene. Genes involved in tumor metabolism, like IGF1R, are also differentially expressed in those meningioma subgroups with higher rates of membrane turnover, higher energy demand and increased resistance to apoptosis. These new subgroups of benign meningiomas exhibit different rates of recurrence. This work shows that benign meningioma with metabolic aggressiveness constitute a subgroup of potentially recurrent tumors in which alterations in genes regulating critical features of aggressiveness, like increased angiogenesis or cell invasion, are still no predominant. The determination of these gene expression biosignatures may allow the early detection of clinically aggressive tumors.

  15. Metabolic Profiling of an Echinostoma caproni Infection in the Mouse for Biomarker Discovery

    PubMed Central

    Saric, Jasmina; Li, Jia V.; Wang, Yulan; Keiser, Jennifer; Bundy, Jake G.; Holmes, Elaine; Utzinger, Jürg

    2008-01-01

    Background Metabolic profiling holds promise with regard to deepening our understanding of infection biology and disease states. The objectives of our study were to assess the global metabolic responses to an Echinostoma caproni infection in the mouse, and to compare the biomarkers extracted from different biofluids (plasma, stool, and urine) in terms of characterizing acute and chronic stages of this intestinal fluke infection. Methodology/Principal Findings Twelve female NMRI mice were infected with 30 E. caproni metacercariae each. Plasma, stool, and urine samples were collected at 7 time points up to day 33 post-infection. Samples were also obtained from non-infected control mice at the same time points and measured using 1H nuclear magnetic resonance (NMR) spectroscopy. Spectral data were subjected to multivariate statistical analyses. In plasma and urine, an altered metabolic profile was already evident 1 day post-infection, characterized by reduced levels of plasma choline, acetate, formate, and lactate, coupled with increased levels of plasma glucose, and relatively lower concentrations of urinary creatine. The main changes in the urine metabolic profile started at day 8 post-infection, characterized by increased relative concentrations of trimethylamine and phenylacetylglycine and lower levels of 2-ketoisocaproate and showed differentiation over the course of the infection. Conclusion/Significance The current investigation is part of a broader NMR-based metabonomics profiling strategy and confirms the utility of this approach for biomarker discovery. In the case of E. caproni, a diagnosis based on all three biofluids would deliver the most comprehensive fingerprint of an infection. For practical purposes, however, future diagnosis might aim at a single biofluid, in which case urine would be chosen for further investigation, based on quantity of biomarkers, ease of sampling, and the degree of differentiation from the non-infected control group. PMID

  16. Transcriptome Profiling of Bovine Milk Oligosaccharide Metabolism Genes Using RNA-Sequencing

    PubMed Central

    Wickramasinghe, Saumya; Hua, Serenus; Rincon, Gonzalo; Islas-Trejo, Alma; German, J. Bruce; Lebrilla, Carlito B.; Medrano, Juan F.

    2011-01-01

    This study examines the genes coding for enzymes involved in bovine milk oligosaccharide metabolism by comparing the oligosaccharide profiles with the expressions of glycosylation-related genes. Fresh milk samples (n = 32) were collected from four Holstein and Jersey cows at days 1, 15, 90 and 250 of lactation and free milk oligosaccharide profiles were analyzed. RNA was extracted from milk somatic cells at days 15 and 250 of lactation (n = 12) and gene expression analysis was conducted by RNA-Sequencing. A list was created of 121 glycosylation-related genes involved in oligosaccharide metabolism pathways in bovine by analyzing the oligosaccharide profiles and performing an extensive literature search. No significant differences were observed in either oligosaccharide profiles or expressions of glycosylation-related genes between Holstein and Jersey cows. The highest concentrations of free oligosaccharides were observed in the colostrum samples and a sharp decrease was observed in the concentration of free oligosaccharides on day 15, followed by progressive decrease on days 90 and 250. Ninety-two glycosylation-related genes were expressed in milk somatic cells. Most of these genes exhibited higher expression in day 250 samples indicating increases in net glycosylation-related metabolism in spite of decreases in free milk oligosaccharides in late lactation milk. Even though fucosylated free oligosaccharides were not identified, gene expression indicated the likely presence of fucosylated oligosaccharides in bovine milk. Fucosidase genes were expressed in milk and a possible explanation for not detecting fucosylated free oligosaccharides is the degradation of large fucosylated free oligosaccharides by the fucosidases. Detailed characterization of enzymes encoded by the 92 glycosylation-related genes identified in this study will provide the basic knowledge for metabolic network analysis of oligosaccharides in mammalian milk. These candidate genes will guide

  17. Intraspecific variability in allelopathy of Heracleum mantegazzianum is linked to the metabolic profile of root exudates.

    PubMed

    Jandová, Kateřina; Dostál, Petr; Cajthaml, Tomáš; Kameník, Zdeněk

    2015-04-01

    Allelopathy may drive invasions of some exotic plants, although empirical evidence for this theory remains largely inconclusive. This could be related to the large intraspecific variability of chemically mediated plant-plant interactions, which is poorly studied. This study addressed intraspecific variability in allelopathy of Heracleum mantegazzianum (giant hogweed), an invasive species with a considerable negative impact on native communities and ecosystems. Bioassays were carried out to test the alleopathic effects of H. mantegazzianum root exudates on germination of Arabidopsis thaliana and Plantago lanceolata. Populations of H. mantegazzianum from the Czech Republic were sampled and variation in the phytotoxic effects of the exudates was partitioned between areas, populations within areas, and maternal lines. The composition of the root exudates was determined by metabolic profiling using ultra-high-performance liquid chromatography with time-of-flight mass spectrometry, and the relationships between the metabolic profiles and the effects observed in the bioassays were tested using orthogonal partial least-squares analysis. Variance partitioning indicated that the highest variance in phytotoxic effects was within populations. The inhibition of germination observed in the bioassay for the co-occurring native species P. lanceolata could be predicted by the metabolic profiles of the root exudates of particular maternal lines. Fifteen compounds associated with this inhibition were tentatively identified. The results present strong evidence that intraspecific variability needs to be considered in research on allelopathy, and suggest that metabolic profiling provides an efficient tool for studying chemically mediated plant-plant interactions whenever unknown metabolites are involved. © The Author 2015. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Untargeted metabolic profiling reveals potential biomarkers in myocardial infarction and its application.

    PubMed

    Yao, Hong; Shi, Peiying; Zhang, Ling; Fan, Xiaohui; Shao, Qing; Cheng, Yiyu

    2010-06-01

    Although some important biomarkers for myocardial injury have been identified, there still lacks a systematic view of the development and progression of myocardial infarction, including enzymatic regulation, metabolite levels, fluxes, etc., which are pivotal to elucidate the physiological mechanism of disease. Here we present an untargeted analytical approach based on gas chromatography coupled with mass spectrometry (GC-MS) to map the temporal metabolic profilings in blood sera of myocardial infarction rat model prepared by left coronary artery ligation. Using XCMS software (http://metlin.scripps.edu/download/), data processing was simplified greatly. We identified the changes in circulating levels of 24 metabolites during the myocardial ischemia. By combination of previous proteomic results, it gives rise to a new insight view of energy metabolism changes referring to anaerobic glycolysis, citric acid cycle, fatty acid beta-oxidation, and some amino acids metabolism. With these altered metabolism pathways as possible drug targets, we validated a role for the presented metabonomic profiling in the systematic understanding of the action mechanism of component-complex medicine herbs, such as Radix Ophiopogonis, a widely-used anti-myocardial ischemia herbal medicine in Asia.

  19. Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose

    PubMed Central

    Zhou, Yue-Yue; Zhu, Xiao-Juan; Li, Rong-Hua; Mu, Chang-Kao; Wang, Chun-Lin; Song, Wei-Wei

    2015-01-01

    D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chromatography/mass spectrometry-based metabonomics and gene expression profiles was used to investigate the changes in transcriptional and metabolic profiles in mimetic aging mice injected with D-galactose. Our findings demonstrated that 48 mRNAs were differentially expressed between control and D-galactose mice, and 51 potential biomarkers were identified at the metabolic level. The effects of D-galactose on aging could be attributed to glucose and 1ipid metabolic disorders, oxidative damage, accumulation of advanced glycation end products (AGEs), reduction in abnormal substance elimination, cell apoptosis, and insulin resistance. PMID:26176541

  20. Gene Transcriptional and Metabolic Profile Changes in Mimetic Aging Mice Induced by D-Galactose.

    PubMed

    Zhou, Yue-Yue; Ji, Xiong-Fei; Fu, Jian-Ping; Zhu, Xiao-Juan; Li, Rong-Hua; Mu, Chang-Kao; Wang, Chun-Lin; Song, Wei-Wei

    2015-01-01

    D-galactose injection has been shown to induce many changes in mice that represent accelerated aging. This mouse model has been widely used for pharmacological studies of anti-aging agents. The underlying mechanism of D-galactose induced aging remains unclear, however, it appears to relate to glucose and 1ipid metabolic disorders. Currently, there has yet to be a study that focuses on investigating gene expression changes in D-galactose aging mice. In this study, integrated analysis of gas chromatography/mass spectrometry-based metabonomics and gene expression profiles was used to investigate the changes in transcriptional and metabolic profiles in mimetic aging mice injected with D-galactose. Our findings demonstrated that 48 mRNAs were differentially expressed between control and D-galactose mice, and 51 potential biomarkers were identified at the metabolic level. The effects of D-galactose on aging could be attributed to glucose and 1ipid metabolic disorders, oxidative damage, accumulation of advanced glycation end products (AGEs), reduction in abnormal substance elimination, cell apoptosis, and insulin resistance.

  1. Metabolic profiling of an alcoholic fatty liver in zebrafish (Danio rerio).

    PubMed

    Jang, Zi-Hey; Chung, Hee-Chung; Ahn, Yun Gyong; Kwon, Yong-Kook; Kim, Jin-Sup; Ryu, Jae-Ho; Ryu, Do Hyun; Kim, Cheol-Hee; Hwang, Geum-Sook

    2012-07-06

    Zebrafish (Danio rerio) is becoming a popular developmental biology model to study diseases and for drug discovery. In this study, we performed proton nuclear magnetic resonance spectroscopy ((1)H-NMR)- and gas chromatography-mass spectrometry (GC/MS)-based metabolic profiling of an alcoholic fatty liver using a zebrafish disease model. We examined metabolic differences between the control and alcoholic fatty liver groups in zebrafish to determine how metabolism in an alcoholic fatty liver is regulated. Multivariate statistical analysis showed a significant difference between the control and alcoholic fatty liver groups. The alcoholic fatty liver group showed increased excretion of isoleucine, acetate, succinate, choline, creatine, acetoacetate, 3-hydroxybutyrate (3HB), ethyl glucuronide (EtG), lactate/pyruvate ratio, fatty acids, and cholesterol, and decreased excretion of citrate, aspartate, tyrosine, glycine, glucose, alanine, betaine, and maltose. Metabolites identified in the fatty liver groups were associated with long-term alcohol consumption, which causes both oxidation-reduction (redox) changes and oxidative stress. This study suggests that global metabolite profiling in a zebrafish model can provide insights into the metabolic changes in an alcoholic fatty liver.

  2. A Pilot Metabolic Profiling Study of Patients With Neonatal Jaundice and Response to Phototherapy.

    PubMed

    Cai, A; Qi, S; Su, Z; Shen, H; Yang, Y; Cai, W; Dai, Y

    2016-08-01

    Phototherapy has been widely used in treating neonatal jaundice, but detailed metabonomic profiles of neonatal jaundice patients and response to phototherapy have not been characterized. Our aim was to depict the serum metabolic characteristics of neonatal jaundice patients relative to controls and changes in response to phototherapy. A (1) H nuclear magnetic resonance (NMR)-based metabonomic approach was employed to study the metabolic profiling of serum from healthy infants (n = 25) and from infants with neonatal jaundice (n = 30) pre- and postphototherapy. The acquired data were processed by multivariate principal component analysis (PCA) and orthogonal partial least-squares-discriminant analysis (OPLS-DA). The PLS-DA and OPLS-DA model identified nine metabolites capable of distinguishing patients from controls. In addition, 28 metabolites such as β-glucose, α-glucose, valine, and pyruvate changed in response to phototherapy. This study offers useful information on metabolic disorders in neonatal jaundice patients and the effects of phototherapy on lipids, amino acid, and energy metabolism.

  3. Method to Identify Saline-Contaminated Electrolyte Profiles

    PubMed Central

    Patel, Devin K.; Naik, Rishi D.; Boyer, Richard B.; Wikswo, John; Vasilevskis, Eduard E.

    2015-01-01

    Background With providers becoming more selective in ordering daily chemistry profiles, it is critical that profiles ordered are accurate. Contaminated electrolyte profiles are an overlooked and potentially dangerous source of inaccurate clinical data. This study aimed to develop a method to accurately identify electrolyte profiles contaminated with normal saline to prevent reporting of erroneous measurements. Methods We conducted a retrospective cohort study of 76,497 electrolyte profiles from 5,032 patients in a deidentified clinical database of all patients in the electronic medical record at Vanderbilt University Medical Center. Five methods to identify errors in quantification based on either deviations from observed concentration distributions or expected numerical changes from saline contamination were developed and tested. Potentially contaminated measurements were validated based on changes in electrolyte concentrations observed in the subsequent sample. Results Identification of erroneous electrolyte profiles based on absolute and percent deviations from normal variation rarely resulted in greater than 50% of identified samples validated as contaminated. A targeted methodology based on expected changes in calcium and chloride concentrations due to saline contamination validated approximately 80% of identified samples when higher thresholds for changes in electrolyte concentration were used and 50% of identified samples when lower thresholds were used. Conclusion Targeted methodology based on changes in chloride and calcium successfully identified electrolyte profiles suspicious for contamination. Implementation of this methodology could prevent misinterpretation of a patient’s clinical course, inappropriate interventions, and unwarranted changes in treatment strategy. PMID:25719332

  4. Metagenomic and Metabolic Profiling of Nonlithifying and Lithifying Stromatolitic Mats of Highborne Cay, The Bahamas

    PubMed Central

    Khodadad, Christina L. M.; Foster, Jamie S.

    2012-01-01

    Background Stromatolites are laminated carbonate build-ups formed by the metabolic activity of microbial mats and represent one of the oldest known ecosystems on Earth. In this study, we examined a living stromatolite located within the Exuma Sound, The Bahamas and profiled the metagenome and metabolic potential underlying these complex microbial communities. Methodology/Principal Findings The metagenomes of the two dominant stromatolitic mat types, a nonlithifying (Type 1) and lithifying (Type 3) microbial mat, were partially sequenced and compared. This deep-sequencing approach was complemented by profiling the substrate utilization patterns of the mats using metabolic microarrays. Taxonomic assessment of the protein-encoding genes confirmed previous SSU rRNA analyses that bacteria dominate the metagenome of both mat types. Eukaryotes comprised less than 13% of the metagenomes and were rich in sequences associated with nematodes and heterotrophic protists. Comparative genomic analyses of the functional genes revealed extensive similarities in most of the subsystems between the nonlithifying and lithifying mat types. The one exception was an increase in the relative abundance of certain genes associated with carbohydrate metabolism in the lithifying Type 3 mats. Specifically, genes associated with the degradation of carbohydrates commonly found in exopolymeric substances, such as hexoses, deoxy- and acidic sugars were found. The genetic differences in carbohydrate metabolisms between the two mat types were confirmed using metabolic microarrays. Lithifying mats had a significant increase in diversity and utilization of carbon, nitrogen, phosphorus and sulfur substrates. Conclusion/Significance The two stromatolitic mat types retained similar microbial communities, functional diversity and many genetic components within their metagenomes. However, there were major differences detected in the activity and genetic pathways of organic carbon utilization. These

  5. Metagenomic and metabolic profiling of nonlithifying and lithifying stromatolitic mats of Highborne Cay, The Bahamas.

    PubMed

    Khodadad, Christina L M; Foster, Jamie S

    2012-01-01

    Stromatolites are laminated carbonate build-ups formed by the metabolic activity of microbial mats and represent one of the oldest known ecosystems on Earth. In this study, we examined a living stromatolite located within the Exuma Sound, The Bahamas and profiled the metagenome and metabolic potential underlying these complex microbial communities. The metagenomes of the two dominant stromatolitic mat types, a nonlithifying (Type 1) and lithifying (Type 3) microbial mat, were partially sequenced and compared. This deep-sequencing approach was complemented by profiling the substrate utilization patterns of the mats using metabolic microarrays. Taxonomic assessment of the protein-encoding genes confirmed previous SSU rRNA analyses that bacteria dominate the metagenome of both mat types. Eukaryotes comprised less than 13% of the metagenomes and were rich in sequences associated with nematodes and heterotrophic protists. Comparative genomic analyses of the functional genes revealed extensive similarities in most of the subsystems between the nonlithifying and lithifying mat types. The one exception was an increase in the relative abundance of certain genes associated with carbohydrate metabolism in the lithifying Type 3 mats. Specifically, genes associated with the degradation of carbohydrates commonly found in exopolymeric substances, such as hexoses, deoxy- and acidic sugars were found. The genetic differences in carbohydrate metabolisms between the two mat types were confirmed using metabolic microarrays. Lithifying mats had a significant increase in diversity and utilization of carbon, nitrogen, phosphorus and sulfur substrates. The two stromatolitic mat types retained similar microbial communities, functional diversity and many genetic components within their metagenomes. However, there were major differences detected in the activity and genetic pathways of organic carbon utilization. These differences provide a strong link between the metagenome and the

  6. Distinct age and differentiation-state dependent metabolic profiles of oligodendrocytes under optimal and stress conditions

    PubMed Central

    Fuh, Shih-Chieh; Hossain, Shireen; Almazan, Guillermina; Multhaup, Gerhard; Healy, Luke M.; Kennedy, Timothy E.; Antel, Jack P.

    2017-01-01

    Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress, adult human oligodendrocytes reduce overall energy production rate impacting the capacity to maintain myelination. Here, we directly compare the metabolic profiles of oligodendrocytes derived from adult rat brain with oligodendrocytes newly differentiated in vitro from oligodendrocyte progenitor cells obtained from the post natal rat brain, under both optimal culture and metabolic stress (low/no glucose) conditions. Oxygen consumption and extracellular acidification rates were measured using a Seahorse extracellular flux analyzer. Our findings indicate that under optimal conditions, adult rat oligodendrocytes preferentially use glycolysis whereas newly differentiated post natal rat oligodendrocytes, and the oligodendrocyte progenitor cells from which they are derived, mainly utilize oxidative phosphorylation to produce ATP. Metabolic stress increases the rate of ATP production via oxidative phosphorylation and significantly reduces glycolysis in adult oligodendrocytes. The rate of ATP production was relatively unchanged in newly differentiated post natal oligodendrocytes under these stress conditions, while it was significantly reduced in oligodendrocyte progenitor cells. Our study indicates that both age and maturation influence the metabolic profile under optimal and stressed conditions, emphasizing the need to consider these variables for in vitro studies that aim to model adult human disease. PMID:28792512

  7. Effects of a cocaine hydrolase engineered from human butyrylcholinesterase on metabolic profile of cocaine in rats.

    PubMed

    Chen, Xiabin; Zheng, Xirong; Zhou, Ziyuan; Zhan, Chang-Guo; Zheng, Fang

    2016-11-25

    Accelerating cocaine metabolism through enzymatic hydrolysis at cocaine benzoyl ester is recognized as a promising therapeutic approach for cocaine abuse treatment. Our more recently designed A199S/F227A/S287G/A328W/Y332G mutant of human BChE, denoted as cocaine hydrolase-3 (CocH3), has a considerably improved catalytic efficiency against cocaine and has been proven active in blocking cocaine-induced toxicity and physiological effects. In the present study, we have further characterized the effects of CocH3 on the detailed metabolic profile of cocaine in rats administrated intravenously (IV) with 5 mg/kg cocaine, demonstrating that IV administration of 0.15 mg/kg CocH3 dramatically changed the metabolic profile of cocaine. Without CocH3 administration, the dominant cocaine-metabolizing pathway in rats was cocaine methyl ester hydrolysis to benzoylecgonine (BZE). With the CocH3 administration, the dominant cocaine-metabolizing pathway in rats became cocaine benzoyl ester hydrolysis to ecgonine methyl ester (EME), and the other two metabolic pathways (i.e. cocaine methyl ester hydrolysis to BZE and cocaine oxidation to norcocaine) became insignificant. The CocH3-catalyzed cocaine benzoyl ester hydrolysis to EME was so efficient such that the measured maximum blood cocaine concentration (∼38 ng/ml) was significantly lower than the threshold blood cocaine concentration (∼72 ng/ml) required to produce any measurable physiological effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Change in Metabolic Profile after 1-Year Nutritional-Behavioral Intervention in Obese Children

    PubMed Central

    Verduci, Elvira; Lassandro, Carlotta; Giacchero, Roberta; Miniello, Vito Leonardo; Banderali, Giuseppe; Radaelli, Giovanni

    2015-01-01

    Research findings are inconsistent about improvement of specific cardio-metabolic variables after lifestyle intervention in obese children. The aim of this trial was to evaluate the effect of a 1-year intervention, based on normocaloric diet and physical activity, on body mass index (BMI), blood lipid profile, glucose metabolism and metabolic syndrome. Eighty-five obese children aged ≥6 years were analyzed. The BMI z-score was calculated. Fasting blood samples were analyzed for lipids, insulin and glucose. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated and insulin resistance was defined as HOMA-IR >3.16. HOMA-β%, quantitative insulin sensitivity check index and triglyceride glucose index were calculated. The metabolic syndrome was defined in accordance with the International Diabetes Federation criteria. At the end of intervention children showed a reduction (mean (95% CI)) in BMI z-score (−0.58 (−0.66; −0.50)), triglycerides (−0.35 (−0.45; −0.25) mmol/L) and triglyceride glucose index (−0.29 (−0.37; −0.21)), and an increase in HDL cholesterol (0.06 (0.01; 0.11) mmol/L). Prevalence of insulin resistance declined from 51.8% to 36.5% and prevalence of metabolic syndrome from 17.1% to 4.9%. Nutritional-behavioral interventions can improve the blood lipid profile and insulin sensitivity in obese children, and possibly provide benefits in terms of metabolic syndrome. PMID:26633492

  9. Metabolic pathway profiling of the derivative of important herbal component noscapine.

    PubMed

    Yao, Yonghua; Xiong, Yang

    2016-02-01

    The present study aims to investigate the influence of metabolic behavior by the introduction of bromo atom into the structure of noscapine. Oral gavage of 50 mg/kg bromo-noscapine for 6- to 8-week-old male mice with C57BL/6 background resulted in the detection of the metabolite undergoing cleavage of methylenedioxy group (II), demethylated bromo-noscapine (III, IV), meconine (V), bromo-cotarnine (VI), bisdemethylated bromo-noscapine (VII), and their corresponding glucuronides (G1-G4) in urine, feces, and serum (24 h). In vitro human liver microsomes or mice liver microsomes incubation system can also give the formation of phase I metabolites. Furthermore, the phase I drug-metabolizing enzymes involved in the metabolism of bromo-noscapine was screened. Many CYP isoforms were involved in the formation of metabolite II, and CYP3A4, CYP1A1, CYP2C19, and CYP2D6 were major CYP isoforms. All the determined CYP isoforms showed the catalytic activity towards the formation of metabolites III, V, and VI. The major CYP isoforms involved in the catalytic formation of metabolite IV were CYP2C19, CYP2D6, and CYP2E1. In conclusion, to date, many structural derivatives of noscapine have been synthesized based on the efficiency. However, the metabolic behavior remains to be elucidated, and the present study gave an example through the investigation of metabolic pathway of bromo-noscapine. The introduction of bromo atom into the structure of noscapine did not alter the metabolites profile, but changed the drug-metabolizing enzyme profiles.

  10. Elucidation of Xenobiotic Metabolism Pathways in Human Skin and Human Skin Models by Proteomic Profiling

    PubMed Central

    van Eijl, Sven; Zhu, Zheying; Cupitt, John; Gierula, Magdalena; Götz, Christine; Fritsche, Ellen; Edwards, Robert J.

    2012-01-01

    Background Human skin has the capacity to metabolise foreign chemicals (xenobiotics), but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin. Methodology/Principal Findings Label-free proteomic analysis of whole human skin (10 donors) was applied and analysed using custom-built PROTSIFT software. The results showed the presence of enzymes with a capacity for the metabolism of alcohols through dehydrogenation, aldehydes through dehydrogenation and oxidation, amines through oxidation, carbonyls through reduction, epoxides and carboxylesters through hydrolysis and, of many compounds, by conjugation to glutathione. Whereas protein levels of these enzymes in skin were mostly just 4–10 fold lower than those in liver and sufficient to support metabolism, the levels of cytochrome P450 enzymes were at least 300-fold lower indicating they play no significant role. Four epidermal models of human skin had profiles very similar to one another and these overlapped substantially with that of whole skin. Conclusions/Significance The proteomics profiling approach was successful in producing a comprehensive analysis of the biotransformation characteristics of whole human skin and various in vitro skin models. The results show that skin contains a range of defined enzymes capable of metabolising different classes of chemicals. The degree of similarity of the profiles of the in vitro models indicates their suitability for epidermal toxicity testing. Overall, these results provide a

  11. Thermodynamic-based computational profiling of cellular regulatory control in hepatocyte metabolism.

    PubMed

    Beard, Daniel A; Qian, Hong

    2005-03-01

    Thermodynamic-based constraints on biochemical fluxes and concentrations are applied in concert with mass balance of fluxes in glycogenesis and glycogenolysis in a model of hepatic cell metabolism. Constraint-based modeling methods that facilitate predictions of reactant concentrations, reaction potentials, and enzyme activities are introduced to identify putative regulatory and control sites in biological networks by computing the minimal control scheme necessary to switch between metabolic modes. Computational predictions of control sites in glycogenic and glycogenolytic operational modes in the hepatocyte network compare favorably with known regulatory mechanisms. The developed hepatic metabolic model is used to computationally analyze the impairment of glucose production in von Gierke's and Hers' diseases, two metabolic diseases impacting glycogen metabolism. The computational methodology introduced here can be generalized to identify downstream targets of agonists, to systematically probe possible drug targets, and to predict the effects of specific inhibitors (or activators) on integrated network function.

  12. Development of a Clickable Probe for Profiling of Protein Glutathionylation in the Central Cellular Metabolism of E. coli and Drosophila.

    PubMed

    Feng, Shan; Chen, Yuling; Yang, Fan; Zhang, Lei; Gong, Yiyi; Adilijiang, Gulishana; Gao, Yan; Deng, Haiteng

    2015-11-19

    Protein glutathionylation is an important post-translational modification that regulates many cellular processes, including energy metabolism, signal transduction, and protein homeostasis. Global profiling of glutathionylated proteins (denoted as glutathionylome) is crucial for understanding redox-regulated signal transduction. Here, we developed a novel method based on click reaction and proteomics to enrich and identify the glutathionylated peptides in Escherichia coli and Drosophila lysates, in which 937 and 1,930 potential glutathionylated peptides were identified, respectively. Bioinformatics analysis showed that the cysteine residue next to negatively charged amino acid residues has a higher frequency of glutathionylation. Importantly, we found that most proteins associated with metabolic pathways were glutathionylated and that the glutathionylation sites of metabolic enzymes were highly conserved among different species. Our results indicate that the glutathione analog is a useful tool to characterize protein glutathionylation, and glutathionylation of metabolic enzymes, which play important roles in regulating cellular metabolism, is conserved.

  13. Metabolic scaling in animals: methods, empirical results, and theoretical explanations.

    PubMed

    White, Craig R; Kearney, Michael R

    2014-01-01

    Life on earth spans a size range of around 21 orders of magnitude across species and can span a range of more than 6 orders of magnitude within species of animal. The effect of size on physiology is, therefore, enormous and is typically expressed by how physiological phenomena scale with mass(b). When b ≠ 1 a trait does not vary in direct proportion to mass and is said to scale allometrically. The study of allometric scaling goes back to at least the time of Galileo Galilei, and published scaling relationships are now available for hundreds of traits. Here, the methods of scaling analysis are reviewed, using examples for a range of traits with an emphasis on those related to metabolism in animals. Where necessary, new relationships have been generated from published data using modern phylogenetically informed techniques. During recent decades one of the most controversial scaling relationships has been that between metabolic rate and body mass and a number of explanations have been proposed for the scaling of this trait. Examples of these mechanistic explanations for metabolic scaling are reviewed, and suggestions made for comparing between them. Finally, the conceptual links between metabolic scaling and ecological patterns are examined, emphasizing the distinction between (1) the hypothesis that size- and temperature-dependent variation among species and individuals in metabolic rate influences ecological processes at levels of organization from individuals to the biosphere and (2) mechanistic explanations for metabolic rate that may explain the size- and temperature-dependence of this trait.

  14. Association between muscle mass and adipo-metabolic profile: a cross-sectional study in older subjects

    PubMed Central

    Perna, Simone; Guido, Davide; Grassi, Mario; Rondanelli, Mariangela

    2015-01-01

    Background Sarcopenia, the decrease in muscle mass and function, may lead to various negative health outcomes in elderly. The association among sarcopenia with adiposity and metabolic markers has rarely been studied in the elderly population, with controversial results. The aim of this study is to evaluate this relationship in older subjects. Methods A cross-sectional study was conducted in 290 elderly patients, focusing on the possible association between muscle mass loss, assessed by relative skeletal muscle mass (RSMM), and an adipo-metabolic profile (AMP) defined by adiposity and metabolic biochemical markers. Measurements of body composition were assessed by dual energy X-ray absorptiometry. Biochemical parameters, such as albumin, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total cholesterol, triglycerides, C-reactive protein, and homocysteine and its related markers (folate and vitamin B12) were measured. Using canonical correlation analysis and structural equation modeling, an individual score of AMP was created and correlated with RSMM. Results The AMP–RSMM correlation was equal to +0.642 (95% confidence interval, +0.512 to +0.773; P<0.001). Hence, a negative association between sarcopenia severity and adiposity/metabolic biochemical markers was highlighted. Conclusion This study contained a novel way to examine the relationship between the variables of interest based on a composite index of adiposity and metabolic conditions. Results shed light on the orientation and magnitude of adiposity and metabolic markers in preventing muscle mass loss. There might be a protective effect of adiposity, compatible with the “obesity paradox.” PMID:25759569

  15. Profiling sugar metabolism during fruit development in a peach progeny with different fructose-to-glucose ratios.

    PubMed

    Desnoues, Elsa; Gibon, Yves; Baldazzi, Valentina; Signoret, Véronique; Génard, Michel; Quilot-Turion, Bénédicte

    2014-11-25

    Fruit taste is largely affected by the concentration of soluble sugars and organic acids and non-negligibly by fructose concentration, which is the sweetest-tasting sugar. To date, many studies investigating the sugars in fruit have focused on a specific sugar or enzyme and often on a single variety, but only a few detailed studies addressing sugar metabolism both as a whole and dynamic system are available. In commercial peach fruit, sucrose is the main sugar, followed by fructose and glucose, which have similar levels. Interestingly, low fructose-to-glucose ratios have been observed in wild peach accessions. A cross between wild peach and commercial varieties offers an outstanding possibility to study fruit sugar metabolism. This work provides a large dataset of sugar composition and the capacities of enzymes that are involved in sugar metabolism during peach fruit development and its genetic diversity. A large fraction of the metabolites and enzymes involved in peach sugar metabolism were assayed within a peach progeny of 106 genotypes, of which one quarter displayed a low fructose-to-glucose ratio. This profiling was performed at six stages of growth using high throughput methods. Our results permit drawing a quasi-exhaustive scheme of sugar metabolism in peach. The use of a large number of genotypes revealed a remarkable robustness of enzymatic capacities across genotypes and years, despite strong variations in sugar composition, in particular the fructose-to-glucose ratio, within the progeny. A poor correlation was also found between the enzymatic capacities and the accumulation rates of metabolites. These results invalidate the hypothesis of the straightforward enzymatic control of sugar concentration in peach fruit. Alternative hypotheses concerning the regulation of fructose concentration are discussed based on experimental data. This work lays the foundation for a comprehensive study of the mechanisms involved in sugar metabolism in developing fruit.

  16. Association of pre-pregnancy body mass index with offspring metabolic profile: Analyses of 3 European prospective birth cohorts

    PubMed Central

    Williams, Dylan M.; Kangas, Antti J.; Soininen, Pasi; Jarvelin, Marjo-Riitta

    2017-01-01

    Background A high proportion of women start pregnancy overweight or obese. According to the developmental overnutrition hypothesis, this could lead offspring to have metabolic disruption throughout their lives and thus perpetuate the obesity epidemic across generations. Concerns about this hypothesis are influencing antenatal care. However, it is unknown whether maternal pregnancy adiposity is associated with long-term risk of adverse metabolic profiles in offspring, and if so, whether this association is causal, via intrauterine mechanisms, or explained by shared familial (genetic, lifestyle, socioeconomic) characteristics. We aimed to determine if associations between maternal body mass index (BMI) and offspring systemic cardio-metabolic profile are causal, via intrauterine mechanisms, or due to shared familial factors. Methods and findings We used 1- and 2-stage individual participant data (IPD) meta-analysis, and a negative-control (paternal BMI) to examine the association between maternal pre-pregnancy BMI and offspring serum metabolome from 3 European birth cohorts (offspring age at blood collection: 16, 17, and 31 years). Circulating metabolic traits were quantified by high-throughput nuclear magnetic resonance metabolomics. Results from 1-stage IPD meta-analysis (N = 5327 to 5377 mother-father-offspring trios) showed that increasing maternal and paternal BMI was associated with an adverse cardio-metabolic profile in offspring. We observed strong positive associations with very-low-density lipoprotein (VLDL)-lipoproteins, VLDL-cholesterol (C), VLDL-triglycerides, VLDL-diameter, branched/aromatic amino acids, glycoprotein acetyls, and triglycerides, and strong negative associations with high-density lipoprotein (HDL), HDL-diameter, HDL-C, HDL2-C, and HDL3-C (all P < 0.003). Slightly stronger magnitudes of associations were present for maternal compared with paternal BMI across these associations; however, there was no strong statistical evidence for

  17. Obese Patients With a Binge Eating Disorder Have an Unfavorable Metabolic and Inflammatory Profile.

    PubMed

    Succurro, Elena; Segura-Garcia, Cristina; Ruffo, Mariafrancesca; Caroleo, Mariarita; Rania, Marianna; Aloi, Matteo; De Fazio, Pasquale; Sesti, Giorgio; Arturi, Franco

    2015-12-01

    To evaluate whether obese patients with a binge eating disorder (BED) have an altered metabolic and inflammatory profile related to their eating behaviors compared with non-BED obese.A total of 115 White obese patients consecutively recruited underwent biochemical, anthropometrical evaluation, and a 75-g oral glucose tolerance test. Patients answered the Binge Eating Scale and were interviewed by a psychiatrist. The patients were subsequently divided into 2 groups according to diagnosis: non-BED obese (n = 85) and BED obese (n = 30). Structural equation modeling analysis was performed to elucidate the relation between eating behaviors and metabolic and inflammatory profile.BED obese exhibited significantly higher percentages of altered eating behaviors, body mass index (P < 0.001), waist circumference (P < 0.01), fat mass (P < 0.001), and a lower lean mass (P < 0.001) when compared with non-BED obese. Binge eating disorder obese also had a worse metabolic and inflammatory profile, exhibiting significantly lower high-density lipoprotein cholesterol levels (P < 0.05), and higher levels of glycated hemoglobin (P < 0.01), uric acid (P < 0.05), erythrocyte sedimentation rate (P < 0.001), high-sensitive C-reactive protein (P < 0.01), and white blood cell counts (P < 0.01). Higher fasting insulin (P < 0.01) and higher insulin resistance (P < 0.01), assessed by homeostasis model assessment index and visceral adiposity index (P < 0.001), were observed among BED obese. All differences remained significant after adjusting for body mass index. No significant differences in fasting plasma glucose or 2-hour postchallenge plasma glucose were found. Structural equation modeling analysis confirmed the relation between the altered eating behaviors of BED and the metabolic and inflammatory profile.Binge eating disorder obese exhibited an unfavorable metabolic and inflammatory profile, which is related to their characteristic

  18. In situ metabolic profiling of single cells by laser ablation electrospray ionization mass spectrometry.

    PubMed

    Shrestha, Bindesh; Vertes, Akos

    2009-10-15

    Depending on age, phase in the cell cycle, nutrition, and environmental factors, individual cells exhibit large metabolic diversity. To explore metabolic variations in cell populations, laser ablation electrospray ionization (LAESI) mass spectrometry (MS) was used for the in situ analysis of individual cells at atmospheric pressure. Single cell ablation was achieved by delivering mid-IR laser pulses through the etched tip of a GeO(2)-based glass fiber. Metabolic analysis was performed from single cells and small cell populations of Allium cepa and Narcissus pseudonarcissus bulb epidermis, as well as single eggs of Lytechinus pictus. Of the 332 peaks detected for A. cepa, 35 were assigned to metabolites with the help of accurate ion masses and tandem MS. The metabolic profiles from single cells of the two plant species included a large variety of oligosaccharides including possibly fructans in A. cepa, and alkaloids, e.g., lycorine in N. pseudonarcissus. Analysis of adjacent individual cells with a difference in pigmentation showed that, in addition to essential metabolites found in both variants, the pigmented cells contained anthocyanidins, other flavonoids, and their glucosides. Analysis of single epidermal cells from different scale leaves in an A. cepa bulb showed metabolic differences corresponding to their age. Our results indicate the feasibility of using LAESI-MS for the in situ analysis of metabolites in single cells with potential applications in studying cell differentiation, changes due to disease states, and response to xenobiotics.

  19. Metabolic profile of oxazepam and related benzodiazepines: clinical and forensic aspects.

    PubMed

    Dinis-Oliveira, Ricardo Jorge

    2017-09-14

    Anxiolytic drugs, namely benzodiazepines, are the most commonly used psychoactive substances since anxiety disorders are prevalent mental disorders particularly in the Western world. Oxazepam is a short-acting benzodiazepine and one of the most frequently prescribed anxiolytic drugs. It is also the active metabolite of a wide range of other benzodiazepines, such as diazepam, ketazolam, temazepam, chlordiazepoxide, demoxazepam, halazepam, medazepam, prazepam, pinazepam, and chlorazepate. Therefore, relevant clinical and forensic outocomes may arise, namely those related to interference in driving performance. It is clinically available as a racemic formulation, with S-enantiomer being more active than R-enantiomer. In humans, it is mainly polimorphically metabolized by glucuronide conjugation at the 3-carbon hydroxyl group, yielding stable diastereomeric glucuronides (R- and S-oxazepam glucuronide). Relevant metabolic and stereoselective interspecies differences have been reported. In this work, the pharmacokinetics of oxazepam with particular focus on metabolic pathways is fully reviewed. Moreover, the metabolic profile of other prescribed benzodiazepines that produce oxazepam as a metabolite is also discussed. It is aimed that knowing the metabolism of oxazepam and related benzodiazepines may lead to the development of new analytical strategies for its early detection and help in further toxicological and clinical interpretations.

  20. Metabolomic profiling reveals a finely tuned, starvation-induced metabolic switch in Trypanosoma cruzi epimastigotes.

    PubMed

    Barisón, María Julia; Rapado, Ludmila Nakamura; Merino, Emilio F; Furusho Pral, Elizabeth Mieko; Mantilla, Brian Suarez; Marchese, Letícia; Nowicki, Cristina; Silber, Ariel Mariano; Cassera, Maria Belen

    2017-05-26

    Trypanosoma cruzi, the etiological agent of Chagas disease, is a protozoan parasite with a complex life cycle involving a triatomine insect and mammals. Throughout its life cycle, the T. cruzi parasite faces several alternating events of cell division and cell differentiation in which exponential and stationary growth phases play key biological roles. It is well accepted that arrest of the cell division in the epimastigote stage, both in the midgut of the triatomine insect and in vitro, is required for metacyclogenesis, and it has been previously shown that the parasites change the expression profile of several proteins when entering this quiescent stage. However, little is known about the metabolic changes that epimastigotes undergo before they develop into the metacyclic trypomastigote stage. We applied targeted metabolomics to measure the metabolic intermediates in the most relevant pathways for energy metabolism and oxidative imbalance in exponentially growing and stationary growth-arrested epimastigote parasites. We show for the first time that T. cruzi epimastigotes transitioning from the exponential to the stationary phase exhibit a finely tuned adaptive metabolic mechanism that enables switching from glucose to amino acid consumption, which is more abundant in the stationary phase. This metabolic plasticity appears to be crucial for survival of the T. cruzi parasite in the myriad different environmental conditions to which it is exposed during its life cycle. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Comparative metabolic and lipidomic profiling of human breast cancer cells with different metastatic potentials

    PubMed Central

    Kim, So-Hyun; Kwon, Yeo-Jung; Chun, Young-Jin; Choi, Hyung-Kyoon

    2016-01-01

    This study conducted comprehensive and comparative metabolic and lipidomic profiling of a human epithelial breast cell line (MCF-10A), a slightly metastatic (MCF-7), and a highly metastatic (MDA-MB-231) breast cancer cell line using gas chromatography mass spectrometry (GC-MS) and direct infusion mass spectrometry (DI-MS). Among 39 metabolites identified by GC-MS analysis, xanthine, glucose-6-phosphate, mannose-6-phosphate, guanine, and adenine were selected as prognostic markers of breast cancer metastasis. Major metabolic pathways involved in differentiation of the cell lines were alanine, aspartate, and glutamate metabolism, purine metabolism and glycine, serine, and threonine metabolism. Among 44 intact lipid species identified by DI-MS analysis, the levels of most phospholipids were higher in both metastatic groups than in normal cells. Specifically, the levels of phosphatidylserine (PS) 18:0/20:4, phosphatidylinositol (PI) 18:0/20:4, and phosphatidylcholine (PC) 18:0/20:4 were markedly higher while those of phosphatidylethanolamine (PE) 18:1/18:1 and PI 18:0/18:1 were lower in MDA-MB-231 cells than in MCF-7 cells. A partial-least-squares regression model was developed and validated for predicting the metastatic potential of breast cancer cells. The information obtained in this study will be useful when developing diagnostic tools and for identifying potential therapeutic targets for metastatic breast cancer. PMID:27564096

  2. Glucose Metabolic Profile by Visual Assessment Combined with Statistical Parametric Mapping Analysis in Pediatric Patients with Epilepsy.

    PubMed

    Zhu, Yuankai; Feng, Jianhua; Wu, Shuang; Hou, Haifeng; Ji, Jianfeng; Zhang, Kai; Chen, Qing; Chen, Lin; Cheng, Haiying; Gao, Liuyan; Chen, Zexin; Zhang, Hong; Tian, Mei

    2017-08-01

    PET with (18)F-FDG has been used for presurgical localization of epileptogenic foci; however, in nonsurgical patients, the correlation between cerebral glucose metabolism and clinical severity has not been fully understood. The aim of this study was to evaluate the glucose metabolic profile using (18)F-FDG PET/CT imaging in patients with epilepsy. Methods: One hundred pediatric epilepsy patients who underwent (18)F-FDG PET/CT, MRI, and electroencephalography examinations were included. Fifteen age-matched controls were also included. (18)F-FDG PET images were analyzed by visual assessment combined with statistical parametric mapping (SPM) analysis. The absolute asymmetry index (|AI|) was calculated in patients with regional abnormal glucose metabolism. Results: Visual assessment combined with SPM analysis of (18)F-FDG PET images detected more patients with abnormal glucose metabolism than visual assessment only. The |AI| significantly positively correlated with seizure frequency (P < 0.01) but negatively correlated with the time since last seizure (P < 0.01) in patients with abnormal glucose metabolism. The only significant contributing variable to the |AI| was the time since last seizure, in patients both with hypometabolism (P = 0.001) and with hypermetabolism (P = 0.005). For patients with either hypometabolism (P < 0.01) or hypermetabolism (P = 0.209), higher |AI| values were found in those with drug resistance than with seizure remission. In the post-1-y follow-up PET studies, a significant change of |AI| (%) was found in patients with clinical improvement compared with those with persistence or progression (P < 0.01). Conclusion:(18)F-FDG PET imaging with visual assessment combined with SPM analysis could provide cerebral glucose metabolic profiles in nonsurgical epilepsy patients. |AI| might be used for evaluation of clinical severity and progress in these patients. Patients with a prolonged period of seizure freedom may have more subtle (or no) metabolic

  3. Metabolic profiling of stages of healthy pregnancy in Hu sheep using nuclear magnetic resonance (NMR).

    PubMed

    Sun, Lingwei; Guo, Yixuan; Fan, Yixuan; Nie, Haitao; Wang, Ruocheng; Wang, Feng

    2017-04-01

    Nutrition is one of the most important factors affecting the reproductive performance of animals. Changes in the ovine maternal metabolism during pregnancy are critical to fetal development. To understand the differences in ovine metabolic changes that occur during normal pregnancy, pregnant ewes carrying twin fetuses (n = 8) were selected at 35 days of gestation (dG). All ewes received 100% of National Research Council (NRC) requirements of all nutrients and energy during this experiment. At 50, 70, 90, and 110 dG, maternal plasma samples were collected and designated as one of four corresponding time points (T1, T2, T3, and T4, respectively). Maternal plasma samples were analyzed using (1)H nuclear magnetic resonance spectroscopy to compare their metabolomic profiles among time points. We used multivariate pattern recognition to screen for different metabolites in the plasma of the ewes. The body weight and food intake of the ewes were significantly (P < 0.05) different at the four time points, and increased with the passage of pregnancy time. The principal component analysis model results showed that the metabolic states at time points T2 and T3 moved gradually further away from that at T1 and were furthest away from that at T1 at time point T4. Among the different time points, there were thirteen significantly differential metabolites in the maternal plasma (P < 0.05). These metabolites were closely related to amino acid metabolism and lipid metabolism, which might occur at different time points in pregnant ewes. In particular, newly observed changes in 1-methylhistidine and malonate were the first such changes found in maternal plasma. These results demonstrate that the metabolomics approach has value for evaluating metabolism in pregnancy with advancing gestation. In conclusion, during normal pregnancy in Hu sheep, related metabolites play an important role in amino acid and lipid metabolism for meeting the nutritional demands of pregnant ewes.

  4. Differential Metabolic Profiles during the Albescent Stages of 'Anji Baicha' (Camellia sinensis).

    PubMed

    Li, Chun-Fang; Yao, Ming-Zhe; Ma, Chun-Lei; Ma, Jian-Qiang; Jin, Ji-Qiang; Chen, Liang

    2015-01-01

    'Anji Baicha' is an albino tea cultivar with white shoots at low air temperature and green shoots at high air temperature in early spring. The metabolite contents in the shoots dynamically vary with the color changes and with shoot development. To investigate the metabolomic variation during the albescent and re-greening stages, gas chromatography-mass spectrometry combined with multivariate analysis were applied to analyze the metabolite profiles in the different color stages during the development of 'Anji Baicha' leaves. The metabolite profiles of three albescent stages, including the yellow-green stage, the early albescent stage, and the late albescent stage, as well as the re-greening stage were distinguished using principal component analysis, revealing that the distinct developmental stages were likely responsible for the observed metabolic differences. Furthermore, a group classification and pairwise discrimination was revealed among the three albescent stages and re-greening stage by partial least squares discriminant analysis. A total of 65 differential metabolites were identified with a variable influence on projection greater than 1. The main differential metabolic pathways of the albescent stages compared with the re-greening stage included carbon fixation in photosynthetic organisms and the phenylpropanoid and flavonoid biosynthesis pathways. Compared with the re-greening stage, the carbohydrate and amino acid metabolic pathways were disturbed during the albescent stages. During the albescent stages, the sugar (fructofuranose), sugar derivative (glucose-1-phosphate) and epicatechin concentrations decreased, whereas the amino acid (mainly glycine, serine, tryptophan, citrulline, glutamine, proline, and valine) concentrations increased. These results reveal the changes in metabolic profiling that occur during the color changes associated with the development of the albino tea plant leaves.

  5. Serum global metabolomics profiling reveals profound metabolic impairments in patients with MPS IIIA and MPS IIIB.

    PubMed

    Fu, Haiyan; Meadows, Aaron S; Pineda, Ricardo J; Mohney, Robert P; Stirdivant, Steve; McCarty, Douglas M

    2017-04-05

    The monogenic defects in specific lysosomal enzymes in mucopolysaccharidosis (MPS) III lead to lysosomal storage of glycosaminoglycans and complex CNS and somatic pathology, for which the detailed mechanisms remain unclear. In this study, serum samples from patients with MPS IIIA (age 2-9 yr) and MPS IIIB (2-13 yr) and healthy controls (age 2-9 yr) were assayed by global metabolomics profiling of 658 metabolites using mass spectrometry. Significant alterations were detected in 423 metabolites in all MPS III patients, of which 366 (86.5%) decreased and 57 (13.5%) increased. Similar profiles were observed when analyzing data from MPS IIIA and MPS IIIB samples separately, with only limited age variations in 36 metabolites. The observed metabolic disturbances in MPS III patients involve virtually all major pathways of amino acid (101/150), peptide (17/21), carbohydrate (19/23), lipid (221/325), nucleotide (15/25), energy (8/9), vitamins and co-factors (8/21), and xenobiotics (34/84) metabolism. Notably, detected serum metabolite decreases involved all key amino acids, all major neurotransmitter pathways, and broad neuroprotective compounds. The elevated metabolites are predominantly lipid derivatives, and also include cysteine metabolites and a fibrinogen peptide fragment, consistent with the status of oxidative stress and inflammation in MPS III. This study demonstrates that the lysosomal glycosaminoglycans storage triggers profound metabolic disturbances in patients with MPS III disorders, leading to severe functional depression of virtually all metabolic pathways, which emerge early during the disease progression. Serum global metabolomics profiling may provide an important and minimally invasive tool for better understanding the disease mechanisms and identification of potential biomarkers for MPS III.

  6. Disposition and metabolic profiling of [(14)C]cerlapirdine using accelerator mass spectrometry.

    PubMed

    Tse, Susanna; Leung, Louis; Raje, Sangeeta; Seymour, Mark; Shishikura, Yoko; Obach, R Scott

    2014-12-01

    Cerlapirdine (SAM-531, PF-05212365) is a selective, potent, full antagonist of the 5-hydroxytryptamine 6 (5-HT6) receptor. Cerlapirdine and other 5-HT6 receptor antagonists have been in clinical development for the symptomatic treatment of Alzheimer's disease. A human absorption, distribution, metabolism, and excretion study was conducted to gain further understanding of the metabolism and disposition of cerlapirdine. Because of the low amount of radioactivity administered, total (14)C content and metabolic profiles in plasma, urine, and feces were determined using accelerator mass spectrometry (AMS). After a single, oral 5-mg dose of [(14)C]cerlapirdine (177 nCi), recovery of total (14)C was almost complete, with feces being the major route of elimination of the administered dose, whereas urinary excretion played a lesser role. The extent of absorption was estimated to be at least 70%. Metabolite profiling in pooled plasma samples showed that unchanged cerlapirdine was the major drug-related component in circulation, representing 51% of total (14)C exposure in plasma. One metabolite (M1, desmethylcerlapirdine) was detected in plasma, and represented 9% of the total (14)C exposure. In vitro cytochrome P450 reaction phenotyping studies showed that M1 was formed primarily by CYP2C8 and CYP3A4. In pooled urine samples, three major drug-related peaks were detected, corresponding to cerlapirdine-N-oxide (M3), cerlapirdine, and desmethylcerlapirdine. In feces, cerlapirdine was the major (14)C component excreted, followed by desmethylcerlapirdine. The results of this study demonstrate that the use of the AMS technique enables comprehensive quantitative elucidation of the disposition and metabolic profiles of compounds administered at a low radioactive dose.

  7. Impact of a synbiotic food on the gut microbial ecology and metabolic profiles

    PubMed Central

    2010-01-01

    Background The human gut harbors a diverse community of microorganisms which serve numerous important functions for the host wellbeing. Functional foods are commonly used to modulate the composition of the gut microbiota contributing to the maintenance of the host health or prevention of disease. In the present study, we characterized the impact of one month intake of a synbiotic food, containing fructooligosaccharides and the probiotic strains Lactobacillus helveticus Bar13 and Bifidobacterium longum Bar33, on the gut microbiota composition and metabolic profiles of 20 healthy subjects. Results The synbiotic food did not modify the overall structure of the gut microbiome, as indicated by Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE). The ability of the probiotic L. helveticus and B. longum strains to pass through the gastrointestinal tract was hypothesized on the basis of real-time PCR data. In spite of a stable microbiota, the intake of the synbiotic food resulted in a shift of the fecal metabolic profiles, highlighted by the Gas Chromatography Mass Spectrometry Solid Phase Micro-Extraction (GC-MS/SPME) analysis. The extent of short chain fatty acids (SCFA), ketones, carbon disulfide and methyl acetate was significantly affected by the synbiotic food consumption. Furthermore, the Canonical discriminant Analysis of Principal coordinates (CAP) of GC-MS/SPME profiles allowed a separation of the stool samples recovered before and after the consumption of the functional food. Conclusion In this study we investigated the global impact of a dietary intervention on the gut ecology and metabolism in healthy humans. We demonstrated that the intake of a synbiotic food leads to a modulation of the gut metabolic activities with a maintenance of the gut biostructure. In particular, the significant increase of SCFA, ketones, carbon disulfide and methyl acetate following the feeding period suggests potential health promoting effects of the

  8. Impact of a synbiotic food on the gut microbial ecology and metabolic profiles.

    PubMed

    Vitali, Beatrice; Ndagijimana, Maurice; Cruciani, Federica; Carnevali, Paola; Candela, Marco; Guerzoni, Maria Elisabetta; Brigidi, Patrizia

    2010-01-07

    The human gut harbors a diverse community of microorganisms which serve numerous important functions for the host wellbeing. Functional foods are commonly used to modulate the composition of the gut microbiota contributing to the maintenance of the host health or prevention of disease. In the present study, we characterized the impact of one month intake of a synbiotic food, containing fructooligosaccharides and the probiotic strains Lactobacillus helveticus Bar13 and Bifidobacterium longum Bar33, on the gut microbiota composition and metabolic profiles of 20 healthy subjects. The synbiotic food did not modify the overall structure of the gut microbiome, as indicated by Polymerase Chain Reaction-Denaturing Gradient Gel Electrophoresis (PCR-DGGE). The ability of the probiotic L. helveticus and B. longum strains to pass through the gastrointestinal tract was hypothesized on the basis of real-time PCR data. In spite of a stable microbiota, the intake of the synbiotic food resulted in a shift of the fecal metabolic profiles, highlighted by the Gas Chromatography Mass Spectrometry Solid Phase Micro-Extraction (GC-MS/SPME) analysis. The extent of short chain fatty acids (SCFA), ketones, carbon disulfide and methyl acetate was significantly affected by the synbiotic food consumption. Furthermore, the Canonical discriminant Analysis of Principal coordinates (CAP) of GC-MS/SPME profiles allowed a separation of the stool samples recovered before and after the consumption of the functional food. In this study we investigated the global impact of a dietary intervention on the gut ecology and metabolism in healthy humans. We demonstrated that the intake of a synbiotic food leads to a modulation of the gut metabolic activities with a maintenance of the gut biostructure. In particular, the significant increase of SCFA, ketones, carbon disulfide and methyl acetate following the feeding period suggests potential health promoting effects of the synbiotic food.

  9. 1H-NMR-based metabolic profiling of a colorectal cancer CT-26 lung metastasis model in mice.

    PubMed

    Li, Yan; Wang, Chunting; Li, Dandan; Deng, Pengchi; Shao, Xiaoni; Hu, Jing; Liu, Chunqi; Jie, Hui; Lin, Yiyun; Li, Zhuoling; Qian, Xinying; Zhang, Huaqin; Zhao, Yinglan

    2017-09-13

    Lung metastasis is an important cause for the low 5-year survival rate of colorectal cancer patients. Understanding the metabolic profile of lung metastasis of colorectal cancer is important for developing molecular diagnostic and therapeutic approaches. We carried out the metabonomic profiling of lung tissue samples on a mouse lung metastasis model of colorectal cancer using 1H-nuclear magnetic resonance (1H-NMR). The lung tissues of mice were collected at different intervals after marine colon cancer cell line CT-26 was intravenously injected into BALB/c mice. The distinguishing metabolites of lung tissue were investigated using 1H-NMR-based metabonomic assay, which is a highly sensitive and non-destructive method for biomarker identification. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were applied to analyze 1H-NMR profiling data to seek potential biomarkers. All of the 3 analyses achieved excellent separations between the normal and metastasis groups. A total of 42 metabolites were identified, ~12 of which were closely correlated with the process of metastasis from colon to lung. These altered metabolites indicated the disturbance of metabolism in metastatic tumors including glycolysis, TCA cycle, glutaminolysis, choline metabolism and serine biosynthesis. Our findings firstly identified the distinguishing metabolites in mouse colorectal cancer lung metastasis models, and indicated that the metabolite disturbance may be associated with the progression of lung metastasis from colon cancer. The altered metabolites may be potential biomarkers that provide a promising molecular approach for clinical diagnosis and mechanistic study of colorectal cancer with lung metastasis.

  10. Metabolic Profiling of Intact Arabidopsis thaliana Leaves during Circadian Cycle Using 1H High Resolution Magic Angle Spinning NMR

    PubMed Central

    van Schadewijk, R.; de Groot, H. J. M.; Alia, A.

    2016-01-01

    Arabidopsis thaliana is the most widely used model organism for research in plant biology. While significant advances in understanding plant growth and development have been made by focusing on the molecular genetics of Arabidopsis, extracting and understanding the functional framework of metabolism is challenging, both from a technical perspective due to losses and modification during extraction of metabolites from the leaves, and from the biological perspective, due to random variation obscuring how well the function is performed. The purpose of this work is to establish the in vivo metabolic profile directly from the Arabidopsis thaliana leaves without metabolite extraction, to reduce the complexity of the results by multivariate analysis, and to unravel the mitigation of cellular complexity by predominant functional periodicity. To achieve this, we use the circadian cycle that strongly influences metabolic and physiological processes and exerts control over the photosynthetic machinery. High resolution-magic angle spinning nuclear magnetic resonance (HR-MAS NMR) was applied to obtain the metabolic profile directly from intact Arabidopsis leaves. Combining one- and two-dimensional 1H HR-MAS NMR allowed the identification of several metabolites including sugars and amino acids in intact leaves. Multivariate analysis on HR-MAS NMR spectra of leaves throughout the circadian cycle revealed modules of primary metabolites with significant and consistent variations of their molecular components at different time points of the circadian cycle. Since robust photosynthetic performance in plants relies on the functional periodicity of the circadian rhythm, our results show that HR-MAS NMR promises to be an important non-invasive method that can be used for metabolomics of the Arabidopsis thaliana mutants with altered physiology and photosynthetic efficiency. PMID:27662620

  11. Quantitative profiling of folate and one-carbon metabolism in large-scale epidemiological studies by mass spectrometry.

    PubMed

    Ueland, Per Magne; Midttun, Oivind; Windelberg, Amrei; Svardal, Asbjørn; Skålevik, Rita; Hustad, Steinar

    2007-01-01

    Derangements of one-carbon metabolism have been related to the development of chronic diseases. Metabolic profiling as part of epidemiological studies in this area should include intermediates involved in the transfer of one-carbon units, cofactors for the relevant enzymes and markers of inflammation, kidney function and smoking. We established five platforms that measured 6-16 analytes each. Platforms A (gas chromatography-mass spectrometry; GC-MS) and B (gas chromatography-tandem mass spectrometry; GC-MS/MS) involved methylchloroformate derivatization of primary amines, thiols and carboxylic acids. Platform C determined basic compounds by liquid chromatography-tandem mass spectrometry (LC-MS/MS), using an ether-linked phenyl reversed-phase column. Platforms D and E (LC-MS/MS) exploited the efficient ionization and high sensitivity obtained for a wide range of analytes, using a mobile phase containing a high concentration of acetic acid. The chromatographic run times ranged from 3 to 8 min. The analyte concentrations ranged from 0.2 nmol/L to 400 micromol/L. Platforms A and B both measured methylmalonic acid, total homocysteine and related amino acids. Platform B also included sarcosine, cystathionine, tryptophan and kynurenine. Platform C was optimized for the measurement of choline and betaine, but also included arginine, asymmetric and symmetric dimethylarginine and creatinine. A diversity of low abundance compounds mainly occurring in the nanomolar range were measured on platform D. These were vitamin B(2) and B(6) species, neopterin, cotinine and tryptophan metabolites. Platform E measured folates and folate catabolites. Approximately 40 analytes related to one-carbon metabolism were determined in less than 1 mL of plasma/serum using five complementary analytical platforms. As a method control, several metabolites were measured on two or more platforms. Logistics and data handling were carried out by specially designed software. This strategy allows profiling

  12. Urine metabolic profile changes of CCl4-liver fibrosis in rats and intervention effects of Yi Guan Jian Decoction using metabonomic approach

    PubMed Central

    2013-01-01

    Background Yi Guan Jian Decoction (YGJD), a famous Chinese prescription, has long been employed clinically to treat liver fibrosis. However, as of date, there is no report on the effects of YGJD from a metabonomic approach. In this study, a urine metabonomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to study the protective efficacy and metabolic profile changes caused by YGJD in carbon tetrachloride (CCl4)-induced liver fibrosis. Methods Urine samples from Wistar rats of three randomly divided groups (control, model, and YGJD treated) were collected at various time-points, and the metabolic profile changes were analyzed by GC/MS with principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Furthermore, histopathology and biochemical examination were also carried out to ensure the success of CCl4-induced liver fibrosis model. Results Urine metabolic profile studies suggested distinct clustering of the three groups, and YGJD group was much closer to the control group by showing a tendency of recovering towards the control group. Fourteen significantly changed metabolites were found, and YGJD treatment could reverse the levels of these metabolites to normal levels or close to normal levels. Conclusions The current study indicates that the YGJD has significant anti-fibrotic effects on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of energy metabolism, amino acid metabolism, tryptophan metabolism, cytochrome P450 metabolism, and gut microflora metabolism. The metabonomic approach can be recommended to study the pharmacological effect and mechanism of complex Chinese medicines. PMID:23725349

  13. Radical scavenging activity and LC-MS metabolic profiling of petals, stamens, and flowers of Crocus sativus L.

    PubMed

    Montoro, Paola; Maldini, Mariateresa; Luciani, Leonilda; Tuberoso, Carlo I G; Congiu, Francesca; Pizza, Cosimo

    2012-08-01

    Radical scavenging activities of Crocus sativus petals, stamens and entire flowers, which are waste products in the production of the spice saffron, by employing ABTS radical scavenging method, were determined. At the same time, the metabolic profiles of different extract (obtained by petals, stamens and flowers) were obtained by LC-ESI-IT MS (liquid chromatography coupled with electrospray mass spectrometry equipped with Ion Trap analyser). LC-ESI-MS is a techniques largely used nowadays for qualitative fingerprint of herbal extracts and particularly for phenolic compounds. To compare the different extracts under an analytical point of view a specific method for qualitative LC-MS analysis was developed. The high variety of glycosylated flavonoids found in the metabolic profiles could give value to C. sativus petals, stamens and entire flowers. Waste products obtained during saffron production, could represent an interesting source of phenolic compounds, with respect to the high variety of compounds and their free radical scavenging activity. © 2012 Institute of Food Technologists®

  14. Gas chromatographic metabolic profiling: a sensitive tool for functional microbial ecology.

    PubMed

    Coucheney, Elsa; Daniell, Tim J; Chenu, Claire; Nunan, Naoise

    2008-12-01

    Microbial metabolomics, which consists of a non-targeted analysis of the metabolites released from ('exometabolome') or existing in ('endometabolome') a cell has mostly been used to study the metabolism of particular microbes. Metabolomes also represent a picture of microbial activity and we suggest that the exometabolome may also contain pertinent information for studying microbial interaction networks. Gas chromatography coupled to mass spectrometry is the most commonly used technique in metabolomics studies. It allows a wide range of metabolites to be detected but requires the derivatisation of compounds prior to detection. This type of non-targeted analysis can introduce biases to the detection and quantification of the different metabolites, particularly at the extraction and derivatisation steps. The aims of this study, therefore, were to quantify the sources of variability and to test the sensitivity of the GC metabolic profiling approach to small environmental changes such as shifts in temperature. The temperature sensitivity of metabolic profiles was compared with that of catabolic profiles obtained using Biolog microplates. Analytical variability was compared with biological variability by incubating bacterial strains isolated from soil with fructose at 20 degrees C and by replicating each step of the protocol (incubation, extraction and derivatisation). For both the endo- and the exometabolome, more than 70% of the total variability was of biological origin and principal components analysis clearly separated the strains along the first ordination axis. The endometabolome distinguished bacterial strains at the species level only, whereas separation was evident at the species and group level with the exometabolome. Temperature had a significant but differential effect on the metabolite production of the bacterial strains whilst their catabolic profiles remained relatively unaffected. The exometabolome was more sensitive to temperature shifts than the

  15. Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome.

    PubMed

    Huang, Rong; Zheng, Jun; Li, Shengxian; Tao, Tao; Ma, Jing; Liu, Wei

    2015-05-01

    To investigate the different characteristics in Chinese Han women with polycystic ovary syndrome, and to analyze the significance of hyperandrogenism in insulin resistance and other metabolic profiles. A cross-sectional study. Medical university hospital. A total of 229 women with polycystic ovary syndrome aged 18-45 years. Women with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided into four groups according to the quartile intervals of free androgen index levels. Comparisons between groups were performed using one-way analysis of variance. Stepwise logistic regression analysis was performed to investigate the association between homeostasis model assessment-insulin resistance and independent variables. Within the four phenotypes, women with phenotype 1 (hyperandrogenism, oligo/anovulation, and polycystic ovaries) exhibited higher total testosterone, free androgen index, androstenedione, low-density lipoprotein, and lower quantitative insulin sensitivity check index (p < 0.05); women with phenotype 4 (oligo/anovulation and polycystic ovaries) showed lower total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance, but higher high-density lipoprotein (p < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance significantly increased, but high-density lipoprotein and quantitative insulin sensitivity check index decreased with the elevation of free androgen index intervals. After adjustment for lipid profiles, free androgen index was significantly associated with homeostasis model assessment-insulin resistance in both lean and overweight/obese women (odds ratio 1.302, p = 0.039 in lean vs. odds ratio 1.132, p = 0.036 in overweight/obese). Phenotypes 1 and 4 represent groups with the most and least severe metabolic profiles, respectively. Hyperandrogenism, particularly with elevated free androgen index, is likely a key contributing

  16. Muscle Transcriptional Profile Based on Muscle Fiber, Mitochondrial Respiratory Activity, and Metabolic Enzymes

    PubMed Central

    Liu, Xuan; Du, Yang; Trakooljul, Nares; Brand, Bodo; Muráni, Eduard; Krischek, Carsten; Wicke, Michael; Schwerin, Manfred; Wimmers, Klaus; Ponsuksili, Siriluck

    2015-01-01

    Skeletal muscle is a highly metabolically active tissue that both stores and consumes energy. Important biological pathways that affect energy metabolism and metabolic fiber type in muscle cells may be identified through transcriptomic profiling of the muscle, especially ante mortem. Here, gene expression was investigated in malignant hyperthermia syndrome (MHS)-negative Duroc and Pietrian (PiNN) pigs significantly differing for the muscle fiber types slow-twitch-oxidative fiber (STO) and fast-twitch-oxidative fiber (FTO) as well as mitochondrial activity (succinate-dependent state 3 respiration rate). Longissimus muscle samples were obtained 24 h before slaughter and profiled using cDNA microarrays. Differential gene expression between Duroc and PiNN muscle samples were associated with protein ubiquitination, stem cell pluripotency, amyloid processing, and 3-phosphoinositide biosynthesis and degradation pathways. In addition, weighted gene co-expression network analysis within both breeds identified several co-expression modules that were associated with the proportion of different fiber types, mitochondrial respiratory activity, and ATP metabolism. In particular, Duroc results revealed strong correlations between mitochondrion-associated co-expression modules and STO (r = 0.78), fast-twitch glycolytic fiber (r = -0.98), complex I (r=0.72) and COX activity (r = 0.86). Other pathways in the protein-kinase-activity enriched module were positively correlated with STO (r=0.93), while negatively correlated with FTO (r = -0.72). In contrast to PiNN, co-expression modules enriched in macromolecule catabolic process, actin cytoskeleton, and transcription activator activity were associated with fiber types, mitochondrial respiratory activity, and metabolic enzyme activities. Our results highlight the importance of mitochondria for the oxidative capacity of porcine muscle and for breed-dependent molecular pathways in muscle cell fibers. PMID:26681915

  17. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    PubMed Central

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors. PMID:24971025

  18. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork.

    PubMed

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors.

  19. Metabolic profiling of a range of peach fruit varieties reveals high metabolic diversity and commonalities and differences during ripening.

    PubMed

    Monti, Laura L; Bustamante, Claudia A; Osorio, Sonia; Gabilondo, Julieta; Borsani, Julia; Lauxmann, Martin A; Maulión, Evangelina; Valentini, Gabriel; Budde, Claudio O; Fernie, Alisdair R; Lara, María V; Drincovich, María F

    2016-01-01

    Peach (Prunus persica) fruits from different varieties display differential organoleptic and nutritional properties, characteristics related to their chemical composition. Here, chemical biodiversity of peach fruits from fifteen varieties, at harvest and after post-harvest ripening, was explored by gas chromatography-mass spectrometry. Metabolic profiling revealed that metabolites involved in organoleptic properties (sugars, organic and amino acids), stress tolerance (raffinose, galactinol, maltitol), and with nutritional properties (amino, caffeoylquinic and dehydroascorbic acids) displayed variety-dependent levels. Peach varieties clustered into four groups: two groups of early-harvest varieties with higher amino acid levels; two groups of mid- and late-harvest varieties with higher maltose levels. Further separation was mostly dependent on organic acids/raffinose levels. Variety-dependent and independent metabolic changes associated with ripening were detected; which contribute to chemical diversity or can be used as ripening markers, respectively. The great variety-dependent diversity in the content of metabolites that define fruit quality reinforces metabolomics usage as a tool to assist fruit quality improvement in peach. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Identifying the Preferred Subset of Enzymatic Profiles in Nonlinear Kinetic Metabolic Models via Multiobjective Global Optimization and Pareto Filters

    PubMed Central

    Pozo, Carlos; Guillén-Gosálbez, Gonzalo; Sorribas, Albert; Jiménez, Laureano

    2012-01-01

    Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the

  1. Identifying the preferred subset of enzymatic profiles in nonlinear kinetic metabolic models via multiobjective global optimization and Pareto filters.

    PubMed

    Pozo, Carlos; Guillén-Gosálbez, Gonzalo; Sorribas, Albert; Jiménez, Laureano

    2012-01-01

    Optimization models in metabolic engineering and systems biology focus typically on optimizing a unique criterion, usually the synthesis rate of a metabolite of interest or the rate of growth. Connectivity and non-linear regulatory effects, however, make it necessary to consider multiple objectives in order to identify useful strategies that balance out different metabolic issues. This is a fundamental aspect, as optimization of maximum yield in a given condition may involve unrealistic values in other key processes. Due to the difficulties associated with detailed non-linear models, analysis using stoichiometric descriptions and linear optimization methods have become rather popular in systems biology. However, despite being useful, these approaches fail in capturing the intrinsic nonlinear nature of the underlying metabolic systems and the regulatory signals involved. Targeting more complex biological systems requires the application of global optimization methods to non-linear representations. In this work we address the multi-objective global optimization of metabolic networks that are described by a special class of models based on the power-law formalism: the generalized mass action (GMA) representation. Our goal is to develop global optimization methods capable of efficiently dealing with several biological criteria simultaneously. In order to overcome the numerical difficulties of dealing with multiple criteria in the optimization, we propose a heuristic approach based on the epsilon constraint method that reduces the computational burden of generating a set of Pareto optimal alternatives, each achieving a unique combination of objectives values. To facilitate the post-optimal analysis of these solutions and narrow down their number prior to being tested in the laboratory, we explore the use of Pareto filters that identify the preferred subset of enzymatic profiles. We demonstrate the usefulness of our approach by means of a case study that optimizes the

  2. Detection of selective antibacterial peptides by the Polarity Profile method.

    PubMed

    Polanco, Carlos; Buhse, Thomas; Samaniego, José Lino; Castañón-González, Jorge Alberto

    2013-01-01

    Antimicrobial peptides occupy a prominent place in the production of pharmaceuticals, because of their effective contribution to the protection of the immune system against almost all types of pathogens. These peptides are thoroughly studied by computational methods designed to shed light on their main functions. In this paper, we propose a computational approach, named the Polarity Profile method that represents an improvement to the former Polarity Index method. The Polarity Profile method is very effective in detecting the subgroup of antibacterial peptides called selective cationic amphipathic antibacterial peptides (SCAAP) that show high toxicity towards bacterial membranes and exhibit almost zero toxicity towards mammalian cells. Our study was restricted to the peptides listed in the antimicrobial peptides database (APD2) of December 19, 2012. Performance of the Polarity Profile method is demonstrated through a comparison to the former Polarity Index method by using the same sets of peptides. The efficiency of the Polarity Profile method exceeds 85% taking into account the false positive and/or false negative peptides.

  3. Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression.

    PubMed

    Jia, Hong-Mei; Li, Qi; Zhou, Chao; Yu, Meng; Yang, Yong; Zhang, Hong-Wu; Ding, Gang; Shang, Hai; Zou, Zhong-Mei

    2016-03-23

    Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury.

  4. Metabolic Profiles of Obesity in American Indians: The Strong Heart Family Study

    PubMed Central

    Best, Lyle G.; Umans, Jason G.; Uppal, Karan; Tran, ViLinh T.; Jones, Dean P.; Lee, Elisa T.; Howard, Barbara V.; Zhao, Jinying

    2016-01-01

    Obesity is a typical metabolic disorder resulting from the imbalance between energy intake and expenditure. American Indians suffer disproportionately high rates of obesity and diabetes. The goal of this study is to identify metabolic profiles of obesity in 431 normoglycemic American Indians participating in the Strong Heart Family Study. Using an untargeted liquid chromatography–mass spectrometry, we detected 1,364 distinct m/z features matched to known compounds in the current metabolomics databases. We conducted multivariate analysis to identify metabolic profiles for obesity, adjusting for standard obesity indicators. After adjusting for covariates and multiple testing, five metabolites were associated with body mass index and seven were associated with waist circumference. Of them, three were associated with both. Majority of the obesity-related metabolites belongs to lipids, e.g., fatty amides, sphingolipids, prenol lipids, and steroid derivatives. Other identified metabolites are amino acids or peptides. Of the nine identified metabolites, five metabolites (oleoylethanolamide, mannosyl-diinositol-phosphorylceramide, pristanic acid, glutamate, and kynurenine) have been previously implicated in obesity or its related pathways. Future studies are warranted to replicate these findings in larger populations or other ethnic groups. PMID:27434237

  5. Inner workings of thrombolites: spatial gradients of metabolic activity as revealed by metatranscriptome profiling

    PubMed Central

    Mobberley, J. M.; Khodadad, C. L. M.; Visscher, P. T.; Reid, R. P.; Hagan, P.; Foster, J. S.

    2015-01-01

    Microbialites are sedimentary deposits formed by the metabolic interactions of microbes and their environment. These lithifying microbial communities represent one of the oldest ecosystems on Earth, yet the molecular mechanisms underlying the function of these communities are poorly understood. In this study, we used comparative metagenomic and metatranscriptomic analyses to characterize the spatial organization of the thrombolites of Highborne Cay, The Bahamas, an actively forming microbialite system. At midday, there were differences in gene expression throughout the spatial profile of the thrombolitic mat with a high abundance of transcripts encoding genes required for photosynthesis, nitrogen fixation and exopolymeric substance production in the upper three mm of the mat. Transcripts associated with denitrification and sulfate reduction were in low abundance throughout the depth profile, suggesting these metabolisms were less active during midday. Comparative metagenomics of the Bahamian thrombolites with other known microbialite ecosystems from across the globe revealed that, despite many shared core pathways, the thrombolites represented genetically distinct communities. This study represents the first time the metatranscriptome of living microbialite has been characterized and offers a new molecular perspective on those microbial metabolisms, and their underlying genetic pathways, that influence the mechanisms of carbonate precipitation in lithifying microbial mat ecosystems. PMID:26213359

  6. Inner workings of thrombolites: spatial gradients of metabolic activity as revealed by metatranscriptome profiling

    NASA Astrophysics Data System (ADS)

    Mobberley, J. M.; Khodadad, C. L. M.; Visscher, P. T.; Reid, R. P.; Hagan, P.; Foster, J. S.

    2015-07-01

    Microbialites are sedimentary deposits formed by the metabolic interactions of microbes and their environment. These lithifying microbial communities represent one of the oldest ecosystems on Earth, yet the molecular mechanisms underlying the function of these communities are poorly understood. In this study, we used comparative metagenomic and metatranscriptomic analyses to characterize the spatial organization of the thrombolites of Highborne Cay, The Bahamas, an actively forming microbialite system. At midday, there were differences in gene expression throughout the spatial profile of the thrombolitic mat with a high abundance of transcripts encoding genes required for photosynthesis, nitrogen fixation and exopolymeric substance production in the upper three mm of the mat. Transcripts associated with denitrification and sulfate reduction were in low abundance throughout the depth profile, suggesting these metabolisms were less active during midday. Comparative metagenomics of the Bahamian thrombolites with other known microbialite ecosystems from across the globe revealed that, despite many shared core pathways, the thrombolites represented genetically distinct communities. This study represents the first time the metatranscriptome of living microbialite has been characterized and offers a new molecular perspective on those microbial metabolisms, and their underlying genetic pathways, that influence the mechanisms of carbonate precipitation in lithifying microbial mat ecosystems.

  7. Metabolic Profiles and Free Radical Scavenging Activity of Cordyceps bassiana Fruiting Bodies According to Developmental Stage

    PubMed Central

    Hyun, Sun-Hee; Lee, Seok-Young; Sung, Gi-Ho; Kim, Seong Hwan; Choi, Hyung-Kyoon

    2013-01-01

    The metabolic profiles of Cordyceps bassiana according to fruiting body developmental stage were investigated using gas chromatography-mass spectrometry. We were able to detect 62 metabolites, including 48 metabolites from 70% methanol extracts and 14 metabolites from 100% n-hexane extracts. These metabolites were classified as alcohols, amino acids, organic acids, phosphoric acids, purine nucleosides and bases, sugars, saturated fatty acids, unsaturated fatty acids, or fatty amides. Significant changes in metabolite levels were found according to developmental stage. Relative levels of amino acids, purine nucleosides, and sugars were higher in development stage 3 than in the other stages. Among the amino acids, valine, isoleucine, lysine, histidine, glutamine, and aspartic acid, which are associated with ABC transporters and aminoacyl-tRNA biosynthesis, also showed higher levels in stage 3 samples. The free radical scavenging activities, which were significantly higher in stage 3 than in the other stages, showed a positive correlation with purine nucleoside metabolites such as adenosine, guanosine, and inosine. These results not only show metabolic profiles, but also suggest the metabolic pathways associated with fruiting body development stages in cultivated C. bassiana. PMID:24058459

  8. Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression

    PubMed Central

    Jia, Hong-mei; Li, Qi; Zhou, Chao; Yu, Meng; Yang, Yong; Zhang, Hong-wu; Ding, Gang; Shang, Hai; Zou, Zhong-mei

    2016-01-01

    Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury. PMID:27006086

  9. Metabolic Profiles of Obesity in American Indians: The Strong Heart Family Study.

    PubMed

    Zhao, Qi; Zhu, Yun; Best, Lyle G; Umans, Jason G; Uppal, Karan; Tran, ViLinh T; Jones, Dean P; Lee, Elisa T; Howard, Barbara V; Zhao, Jinying

    2016-01-01

    Obesity is a typical metabolic disorder resulting from the imbalance between energy intake and expenditure. American Indians suffer disproportionately high rates of obesity and diabetes. The goal of this study is to identify metabolic profiles of obesity in 431 normoglycemic American Indians participating in the Strong Heart Family Study. Using an untargeted liquid chromatography-mass spectrometry, we detected 1,364 distinct m/z features matched to known compounds in the current metabolomics databases. We conducted multivariate analysis to identify metabolic profiles for obesity, adjusting for standard obesity indicators. After adjusting for covariates and multiple testing, five metabolites were associated with body mass index and seven were associated with waist circumference. Of them, three were associated with both. Majority of the obesity-related metabolites belongs to lipids, e.g., fatty amides, sphingolipids, prenol lipids, and steroid derivatives. Other identified metabolites are amino acids or peptides. Of the nine identified metabolites, five metabolites (oleoylethanolamide, mannosyl-diinositol-phosphorylceramide, pristanic acid, glutamate, and kynurenine) have been previously implicated in obesity or its related pathways. Future studies are warranted to replicate these findings in larger populations or other ethnic groups.

  10. Effects of Cadmium Exposure on Growth and Metabolic Profile of Bermudagrass [Cynodon dactylon (L.) Pers.

    PubMed Central

    Xie, Yan; Hu, Longxing; Du, Zhimin; Sun, Xiaoyan; Amombo, Erick; Fan, Jibiao; Fu, Jinmin

    2014-01-01

    Metabolic responses to cadmium (Cd) may be associated with variations in Cd tolerance in plants. The objectives of this study were to examine changes in metabolic profiles in bermudagrass in response to Cd stress and to identify predominant metabolites associated with differential Cd tolerance using gas chromatography-mass spectrometry. Two genotypes of bermudagrass with contrasting Cd tolerance were exposed to 0 and 1.5 mM CdSO4 for 14 days in hydroponics. Physiological responses to Cd were evaluated by determining turf quality, growth rate, chlorophyll content and normalized relative transpiration. All these parameters exhibited higher tolerance in WB242 than in WB144. Cd treated WB144 transported more Cd to the shoot than in WB242. The metabolite analysis of leaf polar extracts revealed 39 Cd responsive metabolites in both genotypes, mainly consisting of amino acids, organic acids, sugars, fatty acids and others. A difference in the metabolic profiles was observed between the two bermudagrass genotypes exposed to Cd stress. Seven amino acids (norvaline, glycine, proline, serine, threonine, glutamic acid and gulonic acid), four organic acids (glyceric acid, oxoglutaric acid, citric acid and malic acid,) and three sugars (xylulose, galactose and talose) accumulated more in WB242 than WB144. However, compared to the control, WB144 accumulated higher quantities of sugars than WB242 in the Cd regime. The differential accumulation of these metabolites could be associated with the differential Cd tolerance in bermudagrass. PMID:25545719

  11. Effects of potato spindle tuber viroid infection on tomato metabolic profile.

    PubMed

    Bagherian, Seyed Ali Akbar; Hamzehzarghani, Habiballah; Izadpanah, Keramatollah; Djavaheri, Mohammad

    2016-08-20

    Viroids are the smallest plant pathogens consisting of a single stranded circular RNA molecule with a strong secondary structure, lacking a coat protein or any other proteins. The mechanism of viroid pathogenicity has remained unclear. Recent advances in instrumentation and data mining have made it possible to study the effects of various stresses on primary and secondary metabolisms. Here, we have utilized metabolic profiling approach to show how PSTVd infection alters tomato metabolic profile and the related pathways. Three terminal leaflets of third true leaf of 20-day-old tolerant tomato cultivar 'Moneymaker' were mechanically inoculated by PSTVd intermediate variant cDNAs and samples were taken from eighth leaf, 19days post-inoculation. Metabolites were extracted and analyzed by gas chromatography/mass spectrometry (GC/MS) and subjected to statistical data analysis. Affected pathways were identified by Pathway Tools program and were compared with microarray data previously reported. The study showed that 79 metabolites changed significantly and 23 pathways were identified in relation to these metabolites. Fourteen of these pathways were similar to those reported in other works. The altered pathways in PSTVd infected tomato leaves included, eight cutin and wax biosynthesis, seven pathways that produce defense related compounds, two energy generator pathways, three hormone biosynthesis pathways, two signal transduction pathways, and one nucleotide biosynthesis pathway. Our data on up/down-regulation of pathways supported the data produced on their corresponding gene(s) up/down-regulation. Copyright © 2016 Elsevier GmbH. All rights reserved.

  12. Metabolic profile of nebivolol, a beta-adrenoceptor antagonist with unique characteristics.

    PubMed

    Agabiti Rosei, Enrico; Rizzoni, Damiano

    2007-01-01

    beta-Adrenoceptor antagonists (beta-blockers) have historically been considered an effective and safe option for first-line treatment of hypertension. However, very recently, it has been proposed that beta-blockers should no longer be considered suitable for first-line therapy in the patient with uncomplicated hypertension because of unfavourable morbidity and mortality data. New evidence from recent clinical studies of nebivolol, a third-generation highly selective beta(1)-blocker with additional endothelial nitric oxide (NO)-mediated vasodilating activity, confirms previous findings that this drug differs from other beta-blockers. The combined mechanisms of beta-adrenoceptor antagonism and NO-mediated vasodilation may potentiate the blood pressure-lowering effect of this agent, and confer a broader favourable metabolic profile, which may be clinically relevant for hypertensive patients. The antioxidant properties of nebivolol and its neutral or even favourable effects on both carbohydrate and lipid metabolism are well documented. These properties consistently differentiate nebivolol from nonvasodilating beta-blockers such as atenolol, metoprolol or bisoprolol. Therapeutic indications for beta-blockers include a wide range of co-morbidities found in hypertensive patients, including ischaemic heart disease, tachyarrhythmias and heart failure. Given that the majority of hypertensive patients require more than one drug to control blood pressure, the multiple mechanisms of action and favourable metabolic profile of nebivolol could make it an alternative therapeutic option for hypertensive patients requiring beta-adrenoceptor therapy.

  13. Adenovirus-36 Seropositivity and Its Relation with Obesity and Metabolic Profile in Children

    PubMed Central

    Del Moral-Hernández, Oscar; Salgado-Bernabé, Aralia B.; Guzmán-Guzmán, Iris P.; Salgado-Goytia, Lorenzo; Muñoz-Valle, José F.

    2013-01-01

    The human adenovirus 36 (Ad-36) is causally and correlatively associated in animals and humans, respectively, with increased adiposity and altered metabolic profile. In previous studies, the relationship between Ad-36 seropositivity with obesity was established in adults and children. We evaluated the association of positive antibodies to Ad-36 with obesity and metabolic profile in Mexican children. Seventy-five children with normal-weight and 82 with obesity were studied in this research. All children had a clinic assessment which included weight, height, body circumferences, and skinfold thickness. Laboratory analyzes included triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, and glucose and insulin levels. An enzyme-linked immunosorbent assay (ELISA) was used to determine the antibodies to Ad-36 in the serum samples. The overall Ad-36 seroprevalence was 73.9%. Ad-36 seropositivity had a higher prevalence in obese children than in normal weight group (58.6 versus 41.4%, P = 0.007). Ad-36 seropositivity was associated with obesity (OR = 2.66, P = 0.01) and high-density lipoprotein <40 mg/dL (OR = 2.85, P = 0.03). The Ad-36 seropositive group had greater risk of 4 metabolic abnormalities compared with those children without none alteration. In summary, Ad-36 seropositivity was associated with obesity and low HDL-c levels in the sample of children studied. PMID:24324491

  14. Adenovirus-36 seropositivity and its relation with obesity and metabolic profile in children.

    PubMed

    Parra-Rojas, Isela; Del Moral-Hernández, Oscar; Salgado-Bernabé, Aralia B; Guzmán-Guzmán, Iris P; Salgado-Goytia, Lorenzo; Muñoz-Valle, José F

    2013-01-01

    The human adenovirus 36 (Ad-36) is causally and correlatively associated in animals and humans, respectively, with increased adiposity and altered metabolic profile. In previous studies, the relationship between Ad-36 seropositivity with obesity was established in adults and children. We evaluated the association of positive antibodies to Ad-36 with obesity and metabolic profile in Mexican children. Seventy-five children with normal-weight and 82 with obesity were studied in this research. All children had a clinic assessment which included weight, height, body circumferences, and skinfold thickness. Laboratory analyzes included triglycerides, total cholesterol, high-density lipoprotein, low-density lipoprotein, and glucose and insulin levels. An enzyme-linked immunosorbent assay (ELISA) was used to determine the antibodies to Ad-36 in the serum samples. The overall Ad-36 seroprevalence was 73.9%. Ad-36 seropositivity had a higher prevalence in obese children than in normal weight group (58.6 versus 41.4%, P = 0.007). Ad-36 seropositivity was associated with obesity (OR = 2.66, P = 0.01) and high-density lipoprotein <40 mg/dL (OR = 2.85, P = 0.03). The Ad-36 seropositive group had greater risk of 4 metabolic abnormalities compared with those children without none alteration. In summary, Ad-36 seropositivity was associated with obesity and low HDL-c levels in the sample of children studied.

  15. Effect of probiotics on metabolic profiles in type 2 diabetes mellitus: A meta-analysis of randomized, controlled trials.

    PubMed

    Li, Caifeng; Li, Xin; Han, Hongqiu; Cui, Hailong; Peng, Min; Wang, Guolin; Wang, Zhiqiang

    2016-06-01

    Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease which is imposing heavy burden on global health and economy. Recent studies indicate gut microbiota play important role on the pathogenesis and metabolic disturbance of T2DM. As an effective mean of regulating gut microbiota, probiotics are live micro-organisms that are believed to provide a specific health benefit on the host. Whether probiotic supplementation could improve metabolic profiles by modifying gut microbiota in T2DM or not is still in controversy.The aim of the study is to assess the effect of probiotic supplementation on metabolic profiles in T2DM.We searched PubMed, EMBASE, and Cochrane Library up to 12 April 2016. Two review authors independently assessed study eligibility, extracted data, and evaluated risk of bias of included studies. Data were pooled by using the random-effect model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Heterogeneity was assessed and quantified (I).A total of 12 randomized controlled trials (RCTs) were included. Lipid profiles (n = 508) and fasting blood glucose (FBG) (n = 520) were reported in 9 trials; the homeostasis model of assessment for insulin resistance index (HOMA-IR) (n = 368) and glycosylated hemoglobin (HbA1c) (n = 380) were reported in 6 trials. Probiotics could alleviate FBG (SMD -0.61 mmol/L, 95% CI [-0.92, -0.30], P = 0.0001). Probiotics could increase high-density lipoprotein-cholesterol (HDL-C) (SMD 0.42 mmol/L, 95% CI [0.08, 0.76], P = 0.01). There were no significant differences in low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), HbA1c and HOMA-IR between the treatment group and the control group.Probiotics may improve glycemic control and lipid metabolism in T2DM. Application of probiotic agents might become a new method for glucose management in T2DM.

  16. Raman-based noninvasive metabolic profile evaluation of in vitro bovine embryos

    NASA Astrophysics Data System (ADS)

    dos Santos, Érika Cristina; Martinho, Herculano; Annes, Kelly; da Silva, Thais; Soares, Carlos Alexandre; Leite, Roberta Ferreira; Milazzotto, Marcella Pecora

    2016-07-01

    The timing of the first embryonic cell divisions may predict the ability of an embryo to establish pregnancy. Similarly, metabolic profiles may be markers of embryonic viability. However, in bovine, data about the metabolomics profile of these embryos are still not available. In the present work, we describe Raman-based metabolomic profiles of culture media of bovine embryos with different developmental kinetics (fast x slow) throughout the in vitro culture. The principal component analysis enabled us to classify embryos with different developmental kinetics since they presented specific spectroscopic profiles for each evaluated time point. We noticed that bands at 1076 cm-1 (lipids), 1300 cm-1 (Amide III), and 2719 cm-1 (DNA nitrogen bases) gave the most relevant spectral features, enabling the separation between fast and slow groups. Bands at 1001 cm-1 (phenylalanine) and 2892 cm-1 (methylene group of the polymethylene chain) presented specific patterns related to embryonic stage and can be considered as biomarkers of embryonic development by Raman spectroscopy. The culture media analysis by Raman spectroscopy proved to be a simple and sensitive technique that can be applied with high efficiency to characterize the profiles of in vitro produced bovine embryos with different development kinetics and different stages of development.

  17. A Numerical Method for Synthesizing Atmospheric Temperature and Humidity Profiles.

    NASA Astrophysics Data System (ADS)

    Tatarskaia, Maia S.; Lataitis, Richard J.; Boba Stankov, B.; Tatarskii, Viatcheslav V.

    1998-07-01

    A numerical technique is described for synthesizing realistic atmospheric temperature and humidity profiles. The method uses an ensemble of radiosonde measurements collected at a site of interest. Erroneous profiles are removed by comparing their likelihood with prevailing meteorological conditions. The remaining profiles are decomposed using the method of empirical orthogonal functions. The corresponding eigenprofiles and the statistics of the expansion coefficients are used to numerically generate synthetic profiles that obey the same statistics (i.e., have the same mean, variability, and vertical correlation) as the initial dataset. The technique was applied to a set of approximately 1000 temperature and humidity soundings made in Denver, Colorado, during the winter months of 1991-95. This dataset was divided into four cloud classification categories and daytime and nighttime launches to better characterize typical profiles for the eight cases considered. It was found that 97% of the variance in the soundings could be accounted for by using only five eigenprofiles in the reconstructions. Ensembles of numerically generated profiles can be used to test the accuracy of various retrieval algorithms under controlled conditions not usually available in practice.

  18. A Method for Finding Metabolic Pathways Using Atomic Group Tracking

    PubMed Central

    Zhong, Cheng; Lin, Hai Xiang; Wang, Jianyi

    2017-01-01

    A fundamental computational problem in metabolic engineering is to find pathways between compounds. Pathfinding methods using atom tracking have been widely used to find biochemically relevant pathways. However, these methods require the user to define the atoms to be tracked. This may lead to failing to predict the pathways that do not conserve the user-defined atoms. In this work, we propose a pathfinding method called AGPathFinder to find biochemically relevant metabolic pathways between two given compounds. In AGPathFinder, we find alternative pathways by tracking the movement of atomic groups through metabolic networks and use combined information of reaction thermodynamics and compound similarity to guide the search towards more feasible pathways and better performance. The experimental results show that atomic group tracking enables our method to find pathways without the need of defining the atoms to be tracked, avoid hub metabolites, and obtain biochemically meaningful pathways. Our results also demonstrate that atomic group tracking, when incorporated with combined information of reaction thermodynamics and compound similarity, improves the quality of the found pathways. In most cases, the average compound inclusion accuracy and reaction inclusion accuracy for the top resulting pathways of our method are around 0.90 and 0.70, respectively, which are better than those of the existing methods. Additionally, AGPathFinder provides the information of thermodynamic feasibility and compound similarity for the resulting pathways. PMID:28068354

  19. Taxonomic and predicted metabolic profiles of the human gut microbiome in pre-Columbian mummies.

    PubMed

    Santiago-Rodriguez, Tasha M; Fornaciari, Gino; Luciani, Stefania; Dowd, Scot E; Toranzos, Gary A; Marota, Isolina; Cano, Raul J

    2016-11-01

    Characterization of naturally mummified human gut remains could potentially provide insights into the preservation and evolution of commensal and pathogenic microorganisms, and metabolic profiles. We characterized the gut microbiome of two pre-Columbian Andean mummies dating to the 10-15th centuries using 16S rRNA gene high-throughput sequencing and metagenomics, and compared them to a previously characterized gut microbiome of an 11th century AD pre-Columbian Andean mummy. Our previous study showed that the Clostridiales represented the majority of the bacterial communities in the mummified gut remains, but that other microbial communities were also preserved during the process of natural mummification, as shown with the metagenomics analyses. The gut microbiome of the other two mummies were mainly comprised by Clostridiales or Bacillales, as demonstrated with 16S rRNA gene amplicon sequencing, many of which are facultative anaerobes, possibly consistent with the process of natural mummification requiring low oxygen levels. Metagenome analyses showed the presence of other microbial groups that were positively or negatively correlated with specific metabolic profiles. The presence of sequences similar to both Trypanosoma cruzi and Leishmania donovani could suggest that these pathogens were prevalent in pre-Columbian individuals. Taxonomic and functional profiling of mummified human gut remains will aid in the understanding of the microbial ecology of the process of natural mummification.

  20. Metabolic profile in workers occupationally exposed to arsenic: role of GST polymorphisms.

    PubMed

    Marcos, Ricardo; Martínez, Valeria; Hernández, Alba; Creus, Amadeu; Sekaran, Chandra; Tokunaga, Hiroshi; Quinteros, Domingo

    2006-03-01

    Arsenic is a well-known human carcinogen with a ubiquitous distribution in the natural environment. Chronic exposure to inorganic arsenic involves a biotransformation process that leds to the main excretion of organic methylated metabolites, such as monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), as well as the parental inorganic species. Interindividual variation in arsenic metabolism has been extensively reported, and polymorphisms in genes involved in such process could be related to changes in the arsenic excretion profile and the response to chronic exposures. Our analysis of the metabolic profiles in three groups of workers exposed to different arsenic exposure levels showed high amounts of inorganic arsenic and MMA in the most-exposed workers versus the least-exposed workers, in whom high amounts of DMA were observed. With respect to the role of different genetic polymorphisms in the glutathione S-transferase (GST) genes in the modulation of the urinary profiles, for the overall population only a tendency was just observed between GSTM1 null and MMA excretion as well as between GSTP1 val/val and DMA excretion.

  1. Association between LAP Index (Lipid Accumulation Product) and metabolic profile in hospitalized patients.

    PubMed

    Vieira, Bruna Angelo; Sauer, Patrícia; Marcadenti, Aline; Piovesan, Carla Haas

    2015-06-01

    Lipid Accumulation Product (LAP) Index correlates to cardiovascular risk factors in general population but it has not been tested in hospitalized patients. We aimed to evaluate associations between LAP Index and metabolic profile in a tertiary hospital. Cross-sectional study with 90 inpatients. Lipid profile, fasting glucose, systolic and diastolic blood pressure measurements were obtained from electronic medical records. Weight, height and waist circumferences (WC) were assessed; Body Mass Index (BMI) and LAP Index were calculated. Data were expressed as mean ± standard deviation or percentage. Pearson's correlation and Multiple Linear Regression were used to assess the objectives. Mean age of participants was 55.03 ± 14.86 years and 47.8% (n = 43) were men. After adjustment for sex, age and physic activity LAP Index (log-transformed) was significantly associated with HDL-cholesterol (p < 0.001), fasting glucose (p = 0.02), systolic blood pressure (p = 0.03) and a trend toward total cholesterol (p = 0.07). There are independent association between LAP Index (log-transformed) and metabolic profile in hospitalized patients. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  2. Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes.

    PubMed

    Sadeghian, Saeed; Boroumand, Mohammad Ali; Sotoudeh-Anvari, Maryam; Rabbani, Shahram; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    This experimental study was performed to determine the impact of opium use on serum lipid profile and glucose metabolism in rats with streptozotocin-induced diabetes. To determine the effect of opium, 20 male rats were divided into control (n = 10) and opium-treated (n = 10) groups. After diabetes induction, the animals were investigated for daily glucose measurements for 35 days. Serum lipid profile and haemoglobin A1c (HbA(1c)) were assayed at the baseline (before induction of diabetes) and at 35-day follow-up. The glycaemia levels in the rats treated with opium were similar to the levels measured in the control rats (544.8 +/- 62.2 mg/dl v. 524.6 +/- 50.0 mg/dl, P = 0.434). In addition, there was no difference between the opium-treated rats and control rats in HbA(1c) (6.5 +/- 0.5% v. 6.6 +/- 0.2%, P = 0.714). Compared to the control rats, the serum total cholesterol, high density lipoprotein (HDL), triglyceride and lipoprotein (a) in the test animals were similar. Opium use has no significant effect on glucose metabolism and serum lipid profile in rats with induced diabetes.

  3. Protocol for quality control in metabolic profiling of biological fluids by U(H)PLC-MS.

    PubMed

    Gika, Helen G; Zisi, Chrysostomi; Theodoridis, Georgios; Wilson, Ian D

    2016-01-01

    The process of untargeted metabolic profiling/phenotyping of complex biological matrices, i.e., biological fluids such as blood plasma/serum, saliva, bile, and tissue extracts, provides the analyst with a wide range of challenges. Not the least of these challenges is demonstrating that the acquired data are of "good" quality and provide the basis for more detailed multivariate, and other, statistical analysis necessary to detect, and identify, potential biomarkers that might provide insight into the process under study. Here straightforward and pragmatic "quality control (QC)" procedures are described that allow investigators to monitor the analytical processes employed for global, untargeted, metabolic profiling. The use of this methodology is illustrated with an example from the analysis of human urine where an excel spreadsheet of the preprocessed LC-MS output is provided with embedded macros, calculations and visualization plots that can be used to explore the data. Whilst the use of these procedures is exemplified on human urine samples, this protocol is generally applicable to metabonomic/metabolomic profiling of biofluids, tissue and cell extracts from many sources. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Blood viscosity measurement: an integral method using Doppler ultrasonic profiles

    NASA Astrophysics Data System (ADS)

    Flaud, P.; Bensalah, A.

    2005-12-01

    The aim of this work is to present a new indirect and noninvasive method for the measurement of the Newtonian blood viscosity. Based on an integral form of the axial Navier-Stokes equation, this method is particularly suited for in vivo investigations using ultrasonic arterial blood velocity profiles. Its main advantage is that it is applicable to periodic as well as non periodic flows. Moreover it does not require classical filtering methods enhancing signal to noise ratio of the physiological signals. This method only requires the knowledge of the velocimetric data measured inside a spatially and temporally optimized zone of the Doppler velocity profiles. The results obtained using numerical simulation as well as in vitro or in vivo experiments prove the effectiveness of the method. It is then well adapted to the clinical environment as a systematic quasi on-line method for the measurement of the blood viscosity.

  5. A Metabolic Profiling Strategy for the Dissection of Plant Defense against Fungal Pathogens

    PubMed Central

    Aliferis, Konstantinos A.; Faubert, Denis; Jabaji, Suha

    2014-01-01

    Here we present a metabolic profiling strategy employing direct infusion Orbitrap mass spectrometry (MS) and gas chromatography-mass spectrometry (GC/MS) for the monitoring of soybean's (Glycine max L.) global metabolism regulation in response to Rhizoctonia solani infection in a time-course. Key elements in the approach are the construction of a comprehensive metabolite library for soybean, which accelerates the steps of metabolite identification and biological interpretation of results, and bioinformatics tools for the visualization and analysis of its metabolome. The study of metabolic networks revealed that infection results in the mobilization of carbohydrates, disturbance of the amino acid pool, and activation of isoflavonoid, α-linolenate, and phenylpropanoid biosynthetic pathways of the plant. Components of these pathways include phytoalexins, coumarins, flavonoids, signaling molecules, and hormones, many of which exhibit antioxidant properties and bioactivity helping the plant to counterattack the pathogen's invasion. Unraveling the biochemical mechanism operating during soybean-Rhizoctonia interaction, in addition to its significance towards the understanding of the plant's metabolism regulation under biotic stress, provides valuable insights with potential for applications in biotechnology, crop breeding, and agrochemical and food industries. PMID:25369450

  6. Systems responses of rats to mequindox revealed by metabolic and transcriptomic profiling.

    PubMed

    Zhao, Xiu-Ju; Hao, Fuhua; Huang, Chongyang; Rantalainen, Mattias; Lei, Hehua; Tang, Huiru; Wang, Yulan

    2012-09-07

    Mequindox is used as an antibiotic drug in livestock; however, its toxicity remains largely unclear. Previously, we investigated metabolic responses of mice to mequindox exposure. In order to evaluate dependences of animal species in response to mequindox insult, we present the metabolic consequences of mequindox exposure in a rat model, by employing the combination of metabonomics and transcriptomics. Metabolic profiling of urine revealed that metabolic recovery is achieved for rats exposed to a low or moderate dose of mequindox, whereas high levels of mequindox exposure trigger liver dysfunction, causing no such recovery. We found that mequindox exposure causes suppression of the tricarboxylic acid cycle and stimulation of glycolysis, which is in contrast to a mouse model previously investigated. In addition, mequindox dosage induces promotion of β-oxidation of fatty acids, which was confirmed by elevated expressions of acox1, hsd17b2, and cpt1a in liver. Furthermore, altered levels of N-methylnicotinate, 1-methylnicotinamide, and glutathione disulfide highlighted the promotion of vitamin B3 antioxidative cycle in rats exposed to mequindox. Moreover, mequindox exposure altered levels of gut microbiotal related co-metabolites, suggesting a perturbation of the gut microflora of the host. Our work provides a comprehensive view of the toxicological effects of mequindox, which is important in the usage of mequindox in animal and human food safety.

  7. Metabolic profiling during ex vivo machine perfusion of the human liver.

    PubMed

    Bruinsma, Bote G; Sridharan, Gautham V; Weeder, Pepijn D; Avruch, James H; Saeidi, Nima; Özer, Sinan; Geerts, Sharon; Porte, Robert J; Heger, Michal; van Gulik, Thomas M; Martins, Paulo N; Markmann, James F; Yeh, Heidi; Uygun, Korkut

    2016-03-03

    As donor organ shortages persist, functional machine perfusion is under investigation to improve preservation of the donor liver. The transplantation of donation after circulatory death (DCD) livers is limited by poor outcomes, but its application may be expanded by ex vivo repair and assessment of the organ before transplantation. Here we employed subnormothermic (21 °C) machine perfusion of discarded human livers combined with metabolomics to gain insight into metabolic recovery during machine perfusion. Improvements in energetic cofactors and redox shifts were observed, as well as reversal of ischemia-induced alterations in selected pathways, including lactate metabolism and increased TCA cycle intermediates. We next evaluated whether DCD livers with steatotic and severe ischemic injury could be discriminated from 'transplantable' DCD livers. Metabolomic profiling was able to cluster livers with similar metabolic patterns based on the degree of injury. Moreover, perfusion parameters combined with differences in metabolic factors suggest variable mechanisms that result in poor energy recovery in injured livers. We conclude that machine perfusion combined with metabolomics has significant potential as a clinical instrument for the assessment of preserved livers.

  8. Generalized framework for context-specific metabolic model extraction methods

    PubMed Central

    Robaina Estévez, Semidán; Nikoloski, Zoran

    2014-01-01

    Genome-scale metabolic models (GEMs) are increasingly applied to investigate the physiology not only of simple prokaryotes, but also eukaryotes, such as plants, characterized with compartmentalized cells of multiple types. While genome-scale models aim at including the entirety of known metabolic reactions, mounting evidence has indicated that only a subset of these reactions is active in a given context, including: developmental stage, cell type, or environment. As a result, several methods have been proposed to reconstruct context-specific models from existing genome-scale models by integrating various types of high-throughput data. Here we present a mathematical framework that puts all existing methods under one umbrella and provides the means to better understand their functioning, highlight similarities and differences, and to help users in selecting a most suitable method for an application. PMID:25285097

  9. A New Rapid Method for Measuring the Vertical Head Profile.

    PubMed

    Keller, Carl

    2017-03-01

    This study describes a new technique for measuring the head profile in a geologic formation. The technique provides rapid, low cost information on the depth of water-producing zones and aquitards in heterogeneous aquifers, yielding estimates of hydraulic heads in each zone while identifying any potential for cross contamination between zones. The measurements can be performed in a typical borehole in just a few hours. The procedure uses both the continuous transmissivity profile obtained by the installation (eversion) of a flexible borehole liner into an open borehole and the subsequent removal (inversion) of the same liner from the borehole. The method is possible because of the continuous transmissivity profile (T profile described by Keller et al. 2014) obtained by measuring the rate of liner eversion under a constant driving head. The hydraulic heads of producing zones are measured using the reverse head profile (RHP) method (patent no. 9,008,971) based on a stepwise inversion of the borehole liner. As each interval of the borehole is uncovered by inversion of the liner, the head beneath the liner is allowed to equilibrate to a steady-state value. The individual hydraulic heads contributing to each measurement are calculated using the measured transmissivity for each zone. Application of the RHP method to a sedimentary bedrock borehole in New Jersey verified that it reproduced the head distribution obtained the same day in the same borehole instrumented with a multilevel sampling system.

  10. The relationship of metabolic syndrome and health-promoting lifestyle profiles of Latinos in the Northwest.

    PubMed

    Sutherland, Leonie L; Simonson, Shawn; Weiler, Dawn M; Reis, Janet; Channel, Amara

    2014-01-01

    Latinos are at elevated risk for metabolic syndrome (MetS), a cluster of metabolic factors predictive of cardiovascular disease and diabetes. This study summarizes the association of MetS risk factors with self-reported health behaviors for 225 low-income, Northwest Latino men and women according to age and gender. The Health-Promoting Lifestyle Profile II (HPLP II) in English and Spanish was used to measure the extent to which participants engaged in health-promoting behavior. Biophysical measures included body composition, blood pressure, and fasting venous blood analysis. Men had significantly higher triglycerides, blood glucose, and systolic and diastolic blood pressure readings. Both men and women had central obesity measurements above the recommended cutoffs. There were no statistically significant differences except for physical activity on the HPLP II scores according to level of risk for MetS.

  11. Riluzole prodrugs for melanoma and ALS: design, synthesis, and in vitro metabolic profiling

    PubMed Central

    McDonnell, Mark E.; Vera, Matthew D.; Blass, Benjamin E.; Pelletier, Jeffrey C.; King, Richard C.; Fernandez-Metzler, Carmen; Smith, Garry R.; Wrobel, Jay; Chen, Suzie; Reitz, Allen B.

    2012-01-01

    Riluzole (1) is an approved therapeutic for the treatment of ALS and has also demonstrated antimelanoma activity in metabotropic glutamate GRM1 positive cell lines, a mouse xenograft assay and human clinical trials. Highly variable drug exposure following oral administration among patients, likely due to variable first pass effects from heterogeneous CYP1A2 expression, hinders its clinical use. In an effort to mitigate effects of this clearance pathway and uniformly administer riluzole at efficacious exposure levels, several classes of prodrugs of riluzole were designed, synthesized, and evaluated in multiple in vitro stability assays to predict in vivo drug levels. The optimal prodrug would possess the following profile: stability while transiting the digestive system, stability towards first pass metabolism, and metabolic lability in the plasma releasing riluzole. (S)-O-Benzyl serine derivative 9 was identified as the most promising therapeutically acceptable prodrug. PMID:22892214

  12. Metabolic profile of first and second generation antipsychotics among Chinese patients.

    PubMed

    Lee, Edwin; Chow, Lai-Yin; Leung, Chi-Ming

    2011-02-28

    The metabolic profiles of Chinese patients treated with second-generation antipsychotic (SGA) medication and first-generation antipsychotic (FGA) medication were compared. The sample comprised 99 patients treated with SGA (risperidone, olanzapine and ziprasidone) and 99 with FGA (chlorpromazine, haloperidol and trifluoperazine) from the outpatient clinic of a teaching hospital in Hong Kong. The most frequent psychiatric diagnosis was schizophrenia, followed by affective disorder and other psychiatric diagnoses. Subjects were measured for body weight, body height, fasting lipid and glucose levels. SGA was associated with higher LDL-cholesterol level than FGA. Individual comparison of different antipsychotics showed that patients on olanzapine had the greatest increases in cholesterol and triglycerides among all antipsychotics. The finding suggested SGA, particularly olanzapine, were associated with more metabolic risk factors than first-generation antipsychotics.

  13. Characterization of pu-erh tea using chemical and metabolic profiling approaches.

    PubMed

    Xie, Guoxiang; Ye, Mao; Wang, Yungang; Ni, Yan; Su, Mingming; Huang, Hua; Qiu, Mingfeng; Zhao, Aihua; Zheng, Xiaojiao; Chen, Tianlu; Jia, Wei

    2009-04-22

    In this study, the chemical constituents of pu-erh tea, black tea, and green tea, as well as those of pu-erh tea products of different ages, were analyzed and compared using a chemical profiling approach. Differences in tea processing resulted in differences in the chemical constituents and the color of tea infusions. Human biological responses to pu-erh tea ingestion were also studied by using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) in conjunction with multivariate statistical techniques. Metabolic alterations during and after pu-erh tea ingestion were characterized by increased urinary excretion of 5-hydroxytryptophan, inositol, and 4-methoxyphenylacetic acid, along with reduced excretion of 3-chlorotyrosine and creatinine. This study highlights the potential for metabonomic technology to assess nutritional interventions and is an important step toward a full understanding of pu-erh tea and its influence on human metabolism.

  14. Chronic unpredictable mild stress affects myocardial metabolic profiling of SD rats.

    PubMed

    Zhang, Wen-yuan; Liu, Shao; Li, Huan-de; Cai, Hua-lin

    2012-11-01

    Depression is frequently comorbid with cardiovascular diseases (CVDs), but a full understanding of the mechanisms is still on its way. Chronic unpredictable mild stress (CUMS) model is a commonly used model to mimic clinical depression, here we present a GC/MS-based metabolic profiling approach to investigate myocardial metabolic changes of CUMS SD rats. Principal Component Analysis (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA) were utilized to reveal differences between the model and control group. This study found that molecules proved cardioprotective involving glutamine (P=0.019) and inosine (P=0.013), fatty acid (9,12-octadecadienoic acid, P=0.002; hexadecanoic acid, P=0.006; octadecanoic acid, P=0.030) which serve as the major energy source of heart and collagen molecule precursor proline (P=0.036) had down-regulated in CUMS model group. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Optimization and Application of Direct Infusion Nanoelectrospray HRMS Method for Large-Scale Urinary Metabolic Phenotyping in Molecular Epidemiology

    PubMed Central

    2017-01-01

    Large-scale metabolic profiling requires the development of novel economical high-throughput analytical methods to facilitate characterization of systemic metabolic variation in population phenotypes. We report a fit-for-purpose direct infusion nanoelectrospray high-resolution mass spectrometry (DI-nESI-HRMS) method with time-of-flight detection for rapid targeted parallel analysis of over 40 urinary metabolites. The newly developed 2 min infusion method requires <10 μL of urine sample and generates high-resolution MS profiles in both positive and negative polarities, enabling further data mining and relative quantification of hundreds of metabolites. Here we present optimization of the DI-nESI-HRMS method in a detailed step-by-step guide and provide a workflow with rigorous quality assessment for large-scale studies. We demonstrate for the first time the application of the method for urinary metabolic profiling in human epidemiological investigations. Implementation of the presented DI-nESI-HRMS method enabled cost-efficient analysis of >10 000 24 h urine samples from the INTERMAP study in 12 weeks and >2200 spot urine samples from the ARIC study in <3 weeks with the required sensitivity and accuracy. We illustrate the application of the technique by characterizing the differences in metabolic phenotypes of the USA and Japanese population from the INTERMAP study. PMID:28245357

  16. Metabolic profiling using HPLC allows classification of drugs according to their mechanisms of action in HL-1 cardiomyocytes

    SciTech Connect

    Strigun, Alexander; Wahrheit, Judith; Beckers, Simone; Heinzle, Elmar; Noor, Fozia

    2011-04-15

    Along with hepatotoxicity, cardiotoxic side effects remain one of the major reasons for drug withdrawals and boxed warnings. Prediction methods for cardiotoxicity are insufficient. High content screening comprising of not only electrophysiological characterization but also cellular molecular alterations are expected to improve the cardiotoxicity prediction potential. Metabolomic approaches recently have become an important focus of research in pharmacological testing and prediction. In this study, the culture medium supernatants from HL-1 cardiomyocytes after exposure to drugs from different classes (analgesics, antimetabolites, anthracyclines, antihistamines, channel blockers) were analyzed to determine specific metabolic footprints in response to the tested drugs. Since most drugs influence energy metabolism in cardiac cells, the metabolite 'sub-profile' consisting of glucose, lactate, pyruvate and amino acids was considered. These metabolites were quantified using HPLC in samples after exposure of cells to test compounds of the respective drug groups. The studied drug concentrations were selected from concentration response curves for each drug. The metabolite profiles were randomly split into training/validation and test set; and then analysed using multivariate statistics (principal component analysis and discriminant analysis). Discriminant analysis resulted in clustering of drugs according to their modes of action. After cross validation and cross model validation, the underlying training data were able to predict 50%-80% of conditions to the correct classification group. We show that HPLC based characterisation of known cell culture medium components is sufficient to predict a drug's potential classification according to its mode of action.

  17. [Profile of free fatty acids (FFA) in serum of young Colombians with obesity and metabolic syndrome].

    PubMed

    Bermudez, J A; Velásquez, C M

    2014-12-01

    Obesity produces greater circulation of free fatty acids (FFA). In adults, the FFA composition changes in states of obesity; in adolescents, the results are contradictory. This study compare the FFA profile of obese youth with and without Metabolic Syndrome (MetS) and explore the association between FFA and metabolic alterations of obesity and MetS. A cross-sectional study with 96 young people between 10 and 18 years old was divided into three groups: 1) obese youth with MetS, 2) obese youth without MetS; and 3) adequate weight (AW), matched according to age, gender, pubertal maturation and socioeconomic stratum. The nutritional status was classified according to the body-mass index (BMI), according to the World Health Organization 2007 (WHO, 2007); the waist circumference (WC), adiposity, lipid profile, highly-sensitive reactive C protein (hsRCP), glucose, insulin and insulin resistance (IR), according to the homeostatic model assessment (HOMA Calculator Version 2.2.2). The FFA serum concentration was determined by gas chromatography. Both obese groups had higher adiposity, inflamation (hsRCP), FFA totals and frequency palmitoleic-16:Jn7, compared to AW. The obese with MetS presented more metabolic alterations, a greater amount of dihomo-γ-linolenic (DHGL-20:3n6) and a 20:3n6/18:2n6 relation, indicative of increased activity of A6 desaturase (D6D). The FFA totals, palmitoleic-l6:1n7, DHGL-20:3n6, D6D activity and hsRCP significantly correlated with variables of adiposity, IR and triglicerides. The results in obese with MetS corroborate the association among central obesity, inflammation and increased lipolysis in visceral adipose tissue and metabolic alterations.

  18. BMI and metabolic profile in patients with prolactinoma before and after treatment with dopamine agonists.

    PubMed

    dos Santos Silva, Cintia M; Barbosa, Flavia R P; Lima, Giovanna A B; Warszawski, Leila; Fontes, Rosita; Domingues, Romeu C; Gadelha, Mõnica R

    2011-04-01

    Hyperprolactinemia might be related to weight gain, metabolic syndrome (MS), and insulin resistance (IR). Treatment with dopamine agonist (DA) has been shown to reduce body weight and improve metabolic parameters. The objectives of this study were to determine the prevalence of obesity, overweight, MS, and IR in patients with prolactinoma before and after therapy with DA and to evaluate the relation between prolactin (PRL), body weight, fat distribution, leptin levels, IR, and lipid profile before treatment. In addition, we investigated the correlation of the reduction in PRL levels with weight loss and metabolic profile improvement. Twenty-two patients with prolactinoma completed 6 months of treatment with DA. These patients were submitted to clinical (BMI, waist circumference, blood pressure (BP)), laboratory evaluation (leptin, glucose, low-density lipoprotein (LDL)-cholesterol, and triglyceride (TG) levels) and abdominal computed tomography (CT) before and after treatment. The statistical analyses were done by nonparametric tests. At the beginning of the study, the prevalence of obesity, overweight, MS, and IR was 45, 27, 27, and 18%, respectively. After 6 months of treatment with DA, PRL levels normalized, but no significant difference in BMI was observed. However, there was a significant decrease on homeostasis model assessment of insulin resistance (HOMA(IR)) index, glucose, LDL-cholesterol, and TG levels. This study suggests a possible involvement of prolactinoma on the prevalence of obesity. We should consider that DA may be effective on improving metabolic parameters, and we speculate that a period longer than 6 months of treatment is necessary to conclude whether this drug can interfere in the body weight of patients with prolactinoma.

  19. Metabolic profiles of serum from rats after subchronic exposure to chlorpyrifos and carbaryl.

    PubMed

    Wang, Hui-Ping; Liang, Yu-Jie; Long, Ding-Xin; Chen, Jia-Xiang; Hou, Wei-Yuan; Wu, Yi-Jun

    2009-06-01

    Chlorpyrifos (CPF) and carbaryl (CAR) have been widely used in agricultural and domestic settings. Previous studies have demonstrated that CPF and CAR are generally neurotoxic to mammals, whereas the toxicities of these pesticides to other organs and their potential interactive effects remain unclear. The purpose of this study assessed the alterations of histopathology, biochemical parameters, and metabolic profiles of serum in rats following the treatment with CPF and CAR alone or in combination. No histopathological changes were observed in the liver and kidney tissues. Biochemical analysis of blood showed that alanine aminotransferase and total bilirubin in serum increased slightly in CPF-treated rats as compared to controls. Metabonomic analysis revealed alternations in a number of metabolites involving the metabolism of glucose, free fatty acids, and amino acids in liver mitochondria. The treatment of rats with CPF alone resulted in a decrease in lactate, low- and very low-density lipoprotein (LDL/VLDL), dimethylglycine (DMG), and aspartate. This was accompanied by an increase in isoleucine and leucine, 3-hydroxybutyrate (3-HB), N-acetylglycoprotein (NAC), acetone, succinate, glutamine, choline, creatine, glucose, and amino acids in a dose-dependent manner. Similarly, treatment with a high dose of CAR alone led to a decrease in DMG, aspartate, LDL/VLDL, and dimethylamine and an increase in taurine, glucose, and amino acids. The levels of lactate and LDL/VLDL decreased, while those of 3-HB, NAC, acetone, succinate, and glutamine elevated in the group of rats treated with a mixture of CPF and CAR as compared to the groups of CPF or CAR alone. Our results suggest that subchronic exposure to CPF and CAR alone, or in combination, could cause a disturbance in energy and fatty acid metabolism in the liver mitochondria of rats. Overall, we have shown that analysis of metabolic profiles can make exceptional contributions to the understanding of the individual or mutual

  20. A new method for comparing and matching snow profiles, application for profiles measured by penetrometers

    NASA Astrophysics Data System (ADS)

    Hagenmuller, Pascal; Pilloix, Thibault

    2016-05-01

    Hardness has long been recognized as a good predictor of snow mechanical properties and therefore as an indicator of snowpack stability at the measured point. Portable digital penetrometers enable the amassing of a large number of snow stratigraphic hardness profiles. Numerous probings can be performed to assess the snowpack spatial variability and to compensate for measurement errors. On a decameter scale, continuous internal layers are typically present in the snowpack. The variability in stratigraphic features observed in the measurement set mainly originates from the measured variations in internal layer thickness due to either a real heterogeneity in the snowpack or to errors in depth measurement. For the purpose of real time analysis of snowpack stability, a great amount of data collected by digital penetrometers must be quickly synthesized into a characterization representative of the test site. This paper presents a method with which to match and combine several hardness profiles by automatically adjusting their layer thicknesses. The objectives are to synthesize the information collected by several profiles into one representative profile of the measurement set, disentangle information about hardness and depth variabilities, and quantitatively compare hardness profiles measured by different penetrometers. The method was tested by using co-located hardness profiles measured with three different penetrometers --- the snow micropenetrometer (SMP), the Avatech SP1 and the ramsonde --- during the winter 2014-2015 at two sites in the French Alps. When applied to the SMP profiles of both sites, the method reveals a low spatial variability of hardness properties, which is usually masked by depth variations. The developed algorithm is further used to evaluate the new portable penetrometer SP1. The hardness measured with this instrument is shown to be in good agreement with the SMP measurements, but errors in the recovered depth are notable, with a standard

  1. Metabolic profile of different Italian cultivars of hazelnut (Corylus avellana) by nuclear magnetic resonance spectroscopy.

    PubMed

    Sciubba, Fabio; Di Cocco, Maria Enrica; Gianferri, Raffaella; Impellizzeri, Danilo; Mannina, Luisa; De Salvador, Flavio Roberto; Venditti, Alessandro; Delfini, Maurizio

    2014-01-01

    High-resolution proton NMR spectroscopy was performed on three Italian hazelnut cultivars, Tonda di Giffoni, Mortarella and Tonda Gentile Romana, and it allowed to define their metabolic profile. The hazelnuts were grown in the same pedoclimatic conditions in the Monti Cimini (Latium) area. The samples were obtained by using a modified Bligh-Dyer extraction protocol which did not give rise to artefacts arising from the demolition of macromolecular structures such as proteins and polysaccharides. Metabolites belonging to different chemical classes (amino acids, organic acids, carbohydrates, lipids and miscellaneous compounds) were identified and quantified. The three cultivars were discriminated by means of univariate (ANOVA) and multivariate (PCA) statistical analysis.

  2. In vivo metabolic flux profiling with stable isotopes discriminates sites and quantifies effects of mitochondrial dysfunction in C. elegans

    PubMed Central

    Ostrovsky, Julian; Clarke, Colleen; Preston, Judith; Bennett, Michael J.; Yudkoff, Marc; Xiao, Rui; Falk, Marni J.

    2014-01-01

    Mitochondrial respiratory chain (RC) disease diagnosis is complicated both by an absence of biomarkers that sufficiently divulge all cases and limited capacity to quantify adverse effects across intermediary metabolism. We applied high performance liquid chromatography (HPLC) and mass spectrometry (MS) studies of stable-isotope based precursor–product relationships in the nematode, C. elegans, to interrogate in vivo differences in metabolic flux among distinct genetic models of primary RC defects and closely related metabolic disorders. Methods C. elegans strains studied harbor single nuclear gene defects in complex I, II, or III RC subunits (gas-1, mev-1, isp-1); enzymes involved in coenzyme Q biosynthesis (clk-1), the tricarboxylic acid cycle (TCA, idh-1), or pyruvate metabolism (pdha-1); and central nodes of the nutrient-sensing signaling network that involve insulin response (daf-2) or the sirtuin homologue (sir-2.1). Synchronous populations of 2000 early larval stage worms were fed standard Escherichia coli on nematode growth media plates containing 1,6-13C2-glucose throughout their developmental period, with samples extracted on the first day of adult life in 4% perchloric acid with an internal standard. Quantitation of whole animal free amino acid concentrations and isotopic incorporation into amino and organic acids throughout development was performed in all strains by HPLC and isotope ratio MS, respectively. GC/MS analysis was also performed to quantify absolute isotopic incorporation in all molecular species of key TCA cycle intermediates in gas-1 and N2 adult worms. Results Genetic mutations within different metabolic pathways displayed distinct metabolic profiles. RC complex I (gas-1) and III (isp-1) subunit mutants, together with the coenzyme Q biosynthetic mutant (clk-1), shared a similar amino acid profile of elevated alanine and decreased glutamate. The metabolic signature of the complex II mutant (mev-1) was distinct from that of the other RC

  3. A simple and inexpensive method for muddy shore profiling

    NASA Astrophysics Data System (ADS)

    Chowdhury, Sayedur Rahman; Hossain, M. Shahadat; Sharifuzzaman, S. M.

    2014-11-01

    There are several well-established methods for obtaining beach profiles, and more accurate and precise high-tech methods are emerging. Traditional low-cost methods requiring minimal user skill or training are still popular among professionals, scientists, and coastal zone management practitioners. Simple methods are being developed with a primary focus on sand and gravel beaches. This paper describes a simple, low-cost, manual field method for measuring profiles of beaches, which is particularly suitable for muddy shores. The equipment is a type of flexible U-tube manometer that uses liquid columns in vertical tubes to measure differences in elevation; the supporting frame is constructed from wooden poles with base disks, which hold measuring scales and a PVC tube. The structure was trialed on a mudflat characterized by a 20-40-cm-thick surface layer of silt and clay, located at the Kutubdia Island, Bangladesh. The study results are discussed with notes on the method's applicability, advantages and limitations, and several optional modifications for different scenarios for routine profiling of muddy shores. The equipment can be used by one person or two people, and the accuracy of the method is comparable to those in other methods. The equipment can also be used on sandy or gravel beaches.

  4. HPLC-based metabolic profiling and quality control of leaves of different Panax species

    PubMed Central

    Yang, Seung-Ok; Lee, Sang Won; Kim, Young Ock; Sohn, Sang-Hyun; Kim, Young Chang; Hyun, Dong Yoon; Hong, Yoon Pyo; Shin, Yu Su

    2013-01-01

    Leaves from Panax ginseng Meyer (Korean origin and Chinese origin of Korean ginseng) and P. quinquefolius (American ginseng) were harvested in Haenam province, Korea, and were analyzed to investigate patterns in major metabolites using HPLC-based metabolic profiling. Partial least squares discriminant analysis (PLS-DA) was used to analyze the HPLC chromatogram data. There was a clear separation between Panax species and/or origins from different countries in the PLS-DA score plots. The ginsenoside compounds of Rg1, Re, Rg2, Rb2, Rb3, and Rd in Korean leaves were higher than in Chinese and American ginseng leaves, and the Rb1 level in P. quinquefolius leaves was higher than in P. ginseng (Korean origin or Chinese origin). HPLC chromatogram data coupled with multivariate statistical analysis can be used to profile the metabolite content and undertake quality control of Panax products. PMID:23717177

  5. Serum adipocytokine profile and metabolic syndrome in young adult female dermatomyositis patients

    PubMed Central

    Silva, Marilda Guimarães; Borba, Eduardo Ferreira; de Mello, Suzana Beatriz Veríssimo; Shinjo, Samuel Katsuyuki

    2016-01-01

    OBJECTIVES: To analyse the frequency of metabolic syndrome in young adult female dermatomyositis patients and its possible association with clinical and laboratory dermatomyositis-related features and serum adipocytokines. METHOD: This cross-sectional study included 35 dermatomyositis patients and 48 healthy controls. Metabolic syndrome was defined according to the 2009 Joint Interim Statement. RESULTS: Patient age was comparable in the dermatomyositis and control groups, and the median disease duration was 1.0 year. An increased prevalence of metabolic syndrome was detected in the dermatomyositis group (34.3% vs. 6.3%; p=0.001). In addition, increased serum adiponectin and resistin levels were noted in contrast to lower leptin levels. In dermatomyositis patients, adipocytokine levels were correlated with the levels of total cholesterol, low-density cholesterol, triglycerides and muscle enzymes. A comparison of dermatomyositis patients with (n=12) and without (n=23) syndrome metabolic revealed that adipocytokine levels were also correlated with age, and that dermatomyositis patients with metabolic syndrome tended to have more disease activity despite similar adipocytokine levels. CONCLUSIONS: Metabolic syndrome is highly prevalent in young adult female dermatomyositis patients and is related to age and disease activity. Moreover, increased serum adiponectin and resistin levels were detected in dermatomyositis patients, but lower serum leptin levels were observed. PMID:28076515

  6. The associations between yogurt consumption, diet quality, and metabolic profiles in children in the USA.

    PubMed

    Zhu, Yong; Wang, Huifen; Hollis, James H; Jacques, Paul F

    2015-06-01

    Recent studies have shown that yogurt consumption was associated with better diet quality and a healthier metabolic profile in adults. However, such associations have not been investigated in children. The present study examined the associations in children using data from a nationally representative survey. Data from 5,124 children aged 2-18 years, who participated in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2006 in the USA were analyzed. The frequency of yogurt consumption over 12 months was determined using a validated food frequency questionnaire. Diet quality was assessed by the Healthy Eating Index 2005 (HEI-2005) using one 24-HR dietary recall, and metabolic profiles were obtained from the NHANES laboratory data. It was found that only 33.1 % of children consumed yogurt at least once per week (frequent consumers). Adjusting for covariates, frequent consumers had better diet quality than infrequent consumers, as indicated by a higher HEI-2005 total score (P = 0.04). Frequent yogurt consumption was associated with a lower fasting insulin level (P < 0.001), a lower homeostatic model assessment of insulin resistance (P < 0.001), and a higher quantitative insulin sensitivity check index (P = 0.03). However, yogurt consumption was not associated with body weight, fasting glucose, serum lipid profiles, C-reactive protein, and blood pressures (all P > 0.05). These results suggest that frequent yogurt consumption may contribute to improved diet quality and a healthier insulin profile in children. Future longitudinal studies and clinical trials in children are warranted to explore the health benefits of yogurt consumption.

  7. Vitamin C improves basal metabolic rate and lipid profile in alloxan-induced diabetes mellitus in rats.

    PubMed

    Owu, D U; Antai, A B; Udofia, K H; Obembe, A O; Obasi, K O; Eteng, M U

    2006-12-01

    Diabetes mellitus (DM)is a multi-factorial disease which is characterized by hyperglycaemia, lipoprotein abnormalities and oxidative stress. This study evaluated effect of oral vitamin C administration on basal metabolic rate and lipid profile of alloxan-induced diabetic rats. Vitamin C was administered at 200 mg/kg body wt. by gavage for four weeks to diabetic rats after which the resting metabolic rate and plasma lipid profile was determined. The results showed that vitamin C administration significantly (p less than 0.01) reduced the resting metabolic rate in diabetic rats; and also lowered plasma triglyceride, total cholesterol and low-density lipoprotein cholesterol. These results suggest that the administration of vitamin C in this model of established diabetes mellitus might be beneficial for the restoration of basal metabolic rate and improvement of lipid profile. This may at least in part reduce the risk of cardiovascular events seen in diabetes mellitus.

  8. Metabolic Profiling of a Mapping Population Exposes New Insights in the Regulation of Seed Metabolism and Seed, Fruit, and Plant Relations

    PubMed Central

    Toubiana, David; Semel, Yaniv; Tohge, Takayuki; Beleggia, Romina; Cattivelli, Luigi; Rosental, Leah; Nikoloski, Zoran; Zamir, Dani; Fernie, Alisdair R.; Fait, Aaron

    2012-01-01

    To investigate the regulation of seed metabolism and to estimate the degree of metabolic natural variability, metabolite profiling and network analysis were applied to a collection of 76 different homozygous tomato introgression lines (ILs) grown in the field in two consecutive harvest seasons. Factorial ANOVA confirmed the presence of 30 metabolite quantitative trait loci (mQTL). Amino acid contents displayed a high degree of variability across the population, with similar patterns across the two seasons, while sugars exhibited significant seasonal fluctuations. Upon integration of data for tomato pericarp metabolite profiling, factorial ANOVA identified the main factor for metabolic polymorphism to be the genotypic background rather than the environment or the tissue. Analysis of the coefficient of variance indicated greater phenotypic plasticity in the ILs than in the M82 tomato cultivar. Broad-sense estimate of heritability suggested that the mode of inheritance of metabolite traits in the seed differed from that in the fruit. Correlation-based metabolic network analysis comparing metabolite data for the seed with that for the pericarp showed that the seed network displayed tighter interdependence of metabolic processes than the fruit. Amino acids in the seed metabolic network were shown to play a central hub-like role in the topology of the network, maintaining high interactions with other metabolite categories, i.e., sugars and organic acids. Network analysis identified six exceptionally highly co-regulated amino acids, Gly, Ser, Thr, Ile, Val, and Pro. The strong interdependence of this group was confirmed by the mQTL mapping. Taken together these results (i) reflect the extensive redundancy of the regulation underlying seed metabolism, (ii) demonstrate the tight co-ordination of seed metabolism with respect to fruit metabolism, and (iii) emphasize the centrality of the amino acid module in the seed metabolic network. Finally, the study highlights the added

  9. Metabolic profiling reveals altered pattern of central metabolism in navel orange plants as a result of boron deficiency.

    PubMed

    Liu, Guidong; Dong, Xiaochang; Liu, Leichao; Wu, Lishu; Peng, Shu'ang; Jiang, Cuncang

    2015-04-01

    We focused on the changes of metabolite profiles in navel orange plants under long-term boron (B) deficiency using a gas chromatography-mass spectrometry (GC-MS) approach. Curling of the leaves and leaf chlorosis were observed only in the upper leaves (present before start of the treatment) of B-deficient plants, while the lower leaves (grown during treatment) did not show any visible symptoms. The metabolites with up-accumulation in B-deficient leaves were mainly proline, l-ornithine, lysine, glucoheptonic acid, fucose, fumarate, oxalate, quinate, myo-inositol and allo-inositol, while the metabolites with down-accumulation in B-deficient leaves were mainly serine, asparagine, saccharic acid, citrate, succinate, shikimate and phytol. The levels of glucose and fructose were increased only in the upper leaves by B deficiency, while starch content was increased in all the leaves and in roots. The increased levels of malate, ribitol, gluconic acid and glyceric acid occurred only in the lower leaves of B-deficient plants. The increased levels of phenols only in the upper leaves indicated that the effects of B on phenol metabolism in citrus plants may be a consequence of disruptions in leaf structure. Metabolites with opposite reactions in upper and lower leaves were mainly glutamine, glycine and pyrrole-2-carboxylic acid. To our knowledge, the phenomena of allo-inositol even higher than myo-inositol occurred characterized for the first time in this species. These results suggested that the altered pattern of central metabolism may be either specific or adaptive responses of navel orange plants to B deficiency. © 2014 Scandinavian Plant Physiology Society.

  10. Metabolomic profiling reveals severe skeletal muscle group-specific perturbations of metabolism in aged FBN rats.

    PubMed

    Garvey, Sean M; Dugle, Janis E; Kennedy, Adam D; McDunn, Jonathan E; Kline, William; Guo, Lining; Guttridge, Denis C; Pereira, Suzette L; Edens, Neile K

    2014-06-01

    Mammalian skeletal muscles exhibit age-related adaptive and pathological remodeling. Several muscles in particular undergo progressive atrophy and degeneration beyond median lifespan. To better understand myocellular responses to aging, we used semi-quantitative global metabolomic profiling to characterize trends in metabolic changes between 15-month-old adult and 32-month-old aged Fischer 344 × Brown Norway (FBN) male rats. The FBN rat gastrocnemius muscle exhibits age-dependent atrophy, whereas the soleus muscle, up until 32 months, exhibits markedly fewer signs of atrophy. Both gastrocnemius and soleus muscles were analyzed, as well as plasma and urine. Compared to adult gastrocnemius, aged gastrocnemius showed evidence of reduced glycolytic metabolism, including accumulation of glycolytic, glycogenolytic, and pentose phosphate pathway intermediates. Pyruvate was elevated with age, yet levels of citrate and nicotinamide adenine dinucleotide were reduced, consistent with mitochondrial abnormalities. Indicative of muscle atrophy, 3-methylhistidine and free amino acids were elevated in aged gastrocnemius. The monounsaturated fatty acids oleate, cis-vaccenate, and palmitoleate also increased in aged gastrocnemius, suggesting altered lipid metabolism. Compared to gastrocnemius, aged soleus exhibited far fewer changes in carbohydrate metabolism, but did show reductions in several glycolytic intermediates, fumarate, malate, and flavin adenine dinucleotide. Plasma biochemicals showing the largest age-related increases included glycocholate, heme, 1,5-anhydroglucitol, 1-palmitoleoyl-glycerophosphocholine, palmitoleate, and creatine. These changes suggest reduced insulin sensitivity in aged FBN rats. Altogether, these data highlight skeletal muscle group-specific perturbations of glucose and lipid metabolism consistent with mitochondrial dysfunction in aged FBN rats.

  11. Metabolic Profiles in Cell Lines Infected with Classical Swine Fever Virus

    PubMed Central

    Gou, Hongchao; Zhao, Mingqiu; Yuan, Jin; Xu, Hailuan; Ding, Hongxing; Chen, Jinding

    2017-01-01

    Viruses require energy and biosynthetic precursors from host cells for replication. An understanding of the metabolic interplay between classical swine fever virus (CSFV) and host cells is important for exploring the complex pathological mechanisms of classical swine fever (CSF). In the current study, and for the first time, we utilized an approach involving gas chromatography coupled with mass spectrometry (GC-MS) to examine the metabolic profiles within PK-15 and 3D4/2 cells infected with CSFV. The differential metabolites of PK-15 cells caused by CSFV infection mainly included the decreased levels of glucose 6-phosphate [fold change (FC) = −1.94)] and glyceraldehyde-3-phosphate (FC = −1.83) during glycolysis, ribulose 5-phosphate (FC = −1.51) in the pentose phosphate pathway, guanosine (FC = −1.24) and inosine (FC = −1.16) during purine biosynthesis, but the increased levels of 2-ketoisovaleric acid (FC = 0.63) during the citrate cycle, and ornithine (FC = 0.56) and proline (FC = 0.62) during arginine and proline metabolism. However, metabolite changes caused by CSFV infection in 3D4/2 cells included the reduced glyceraldehyde-3-phosphate (FC = −0.77) and pyruvic acid (FC = −1.42) during glycolysis, 2-ketoglutaric acid (FC = −1.52) in the citrate cycle, and the elevated cytosine (FC = 2.15) during pyrimidine metabolism. Our data showed that CSFV might rebuild cellular metabolic programs, thus aiding viral replication. These findings may be important in developing targets for new biomarkers for the diagnosis and identification of enzyme inhibitors or metabolites as antiviral drugs, or screening viral gene products as vaccines. PMID:28473819

  12. Metabolic Profiles in Cell Lines Infected with Classical Swine Fever Virus.

    PubMed

    Gou, Hongchao; Zhao, Mingqiu; Yuan, Jin; Xu, Hailuan; Ding, Hongxing; Chen, Jinding

    2017-01-01

    Viruses require energy and biosynthetic precursors from host cells for replication. An understanding of the metabolic interplay between classical swine fever virus (CSFV) and host cells is important for exploring the complex pathological mechanisms of classical swine fever (CSF). In the current study, and for the first time, we utilized an approach involving gas chromatography coupled with mass spectrometry (GC-MS) to examine the metabolic profiles within PK-15 and 3D4/2 cells infected with CSFV. The differential metabolites of PK-15 cells caused by CSFV infection mainly included the decreased levels of glucose 6-phosphate [fold change (FC) = -1.94)] and glyceraldehyde-3-phosphate (FC = -1.83) during glycolysis, ribulose 5-phosphate (FC = -1.51) in the pentose phosphate pathway, guanosine (FC = -1.24) and inosine (FC = -1.16) during purine biosynthesis, but the increased levels of 2-ketoisovaleric acid (FC = 0.63) during the citrate cycle, and ornithine (FC = 0.56) and proline (FC = 0.62) during arginine and proline metabolism. However, metabolite changes caused by CSFV infection in 3D4/2 cells included the reduced glyceraldehyde-3-phosphate (FC = -0.77) and pyruvic acid (FC = -1.42) during glycolysis, 2-ketoglutaric acid (FC = -1.52) in the citrate cycle, and the elevated cytosine (FC = 2.15) during pyrimidine metabolism. Our data showed that CSFV might rebuild cellular metabolic programs, thus aiding viral replication. These findings may be important in developing targets for new biomarkers for the diagnosis and identification of enzyme inhibitors or metabolites as antiviral drugs, or screening viral gene products as vaccines.

  13. Disposition and metabolic profiling of the penetration enhancer Azone. I. In vitro studies: Urinary profiles of hamster, rat, monkey, and man

    SciTech Connect

    Wiechers, J.W.; Drenth, B.F.; Adolfsen, F.A.; Prins, L.; de Zeeuw, R.A. )

    1990-05-01

    Chain-labeled {sup 14}C-Azone was intravenously administered to hamster, monkey, and rat, to compare its metabolic profile with that obtained previously in humans after dermal application. Azone-derived radioactivity was excreted predominantly in the urine for both hamster and monkey, which is similar to the disposition in humans. Metabolic profiling in urine revealed extensive systemic metabolism to occur in all species studied. The main fraction of the metabolites was most polar in man, followed by rat, monkey, and hamster. Traces of the parent compound were detectable only in hamster urine. Although some of the polar major human metabolites were also present in rat urine, the animals were unsuitable for collecting metabolites of Azone observed in humans. In rats, complete cleavage of the dodecyl side chain was ruled out by administering Azone that had been labeled at two distinct positions of the molecule. Additionally, oral administration of Azone to rats resulted in the same metabolic profile as intravenous administration, indicating that gastrointestinal metabolism does not occur or is similar to systemic metabolism.

  14. The Antagonistic Effect of Mycotoxins Deoxynivalenol and Zearalenone on Metabolic Profiling in Serum and Liver of Mice

    PubMed Central

    Ji, Jian; Zhu, Pei; Cui, Fangchao; Pi, Fuwei; Zhang, Yinzhi; Li, Yun; Wang, Jiasheng; Sun, Xiulan

    2017-01-01

    Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEN), through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg ZEN, and the combined DON + ZEN with final concentration 2 mg/kg DON and 20 mg/kg ZEN for 21 days, were deconvoluted, aligned and identified with MS DIAL. The data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with variable importance for the projection (VIP) > 1, t-test p value < 0.05. The metabolic pathway analysis was performed with MetaMapp and drawn by CytoScape. Results show that the combined DON and ZEN treatment has an obvious “antagonistic effect” in serum and liver tissue metabolic profiling of mice. The blood biochemical indexes, like alkaline phosphatase, alanine transaminase, and albumin (ALB)/globulin (GLO), reveal a moderated trend in the combined DON + ZEN treatment group, which is consistent with histopathological examination. The metabolic pathway analysis demonstrated that the combined DON and ZEN treatment could down-regulate the valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, and O-glycosyl compounds related glucose metabolism in liver tissue. The metabolic profiling in serum confirmed the finding that the combined DON and ZEN treatment has an “antagonistic effect” on liver metabolism of mice. PMID:28075412

  15. The Antagonistic Effect of Mycotoxins Deoxynivalenol and Zearalenone on Metabolic Profiling in Serum and Liver of Mice.

    PubMed

    Ji, Jian; Zhu, Pei; Cui, Fangchao; Pi, Fuwei; Zhang, Yinzhi; Li, Yun; Wang, Jiasheng; Sun, Xiulan

    2017-01-10

    Metabolic profiling in liver and serum of mice was studied for the combined toxic effects of deoxynivalenol (DON) and zearalenone (ZEN), through gas chromatography mass spectrum. The spectrum of serum and liver sample of mice, treated with individual 2 mg/kg DON, 20 mg/kg ZEN, and the combined DON + ZEN with final concentration 2 mg/kg DON and 20 mg/kg ZEN for 21 days, were deconvoluted, aligned and identified with MS DIAL. The data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with variable importance for the projection (VIP) > 1, t-test p value < 0.05. The metabolic pathway analysis was performed with MetaMapp and drawn by CytoScape. Results show that the combined DON and ZEN treatment has an obvious "antagonistic effect" in serum and liver tissue metabolic profiling of mice. The blood biochemical indexes, like alkaline phosphatase, alanine transaminase, and albumin (ALB)/globulin (GLO), reveal a moderated trend in the combined DON + ZEN treatment group, which is consistent with histopathological examination. The metabolic pathway analysis demonstrated that the combined DON and ZEN treatment could down-regulate the valine, leucine and isoleucine biosynthesis, glycine, serine and threonine metabolism, and O-glycosyl compounds related glucose metabolism in liver tissue. The metabolic profiling in serum confirmed the finding that the combined DON and ZEN treatment has an "antagonistic effect" on liver metabolism of mice.

  16. Multimode Rayleigh wave profiling by hybrid surface and borehole methods

    NASA Astrophysics Data System (ADS)

    Lin, Shibin; Ashlock, Jeramy C.

    2014-05-01

    To improve the accuracy of shallow seismic shear wave velocity profiling, we propose a minimally invasive hybrid surface-and-borehole method that enhances the detection of higher modes of Rayleigh wave dispersion data. The new method combines techniques from the multichannel analysis of surface waves and multichannel simulation with one receiver (MSOR) methods to record components of Rayleigh wave motion at the surface as well as at shallow depths within the soil mass. The performance of the proposed method is demonstrated through computational and experimental studies. We show that individual modes of Rayleigh waves can exhibit different dominant depths at which their motion is most significant. This is demonstrated through a numerical study of eigenvectors of layered soil profiles via the stiffness matrix method, and confirmed by a finite element simulation of the apparent dispersion trends recorded at shallow depths using MSOR. Upon superimposing dispersion data recorded via the receivers at various depths, the resulting multimode dispersion data is used in a multi-objective inverse analysis, for which the difference between experimental and theoretical dispersive phase-velocity spectra are minimized for multiple modes simultaneously. In the numerical study, we demonstrate that the resulting inverted profiles and theoretical dispersion data have improved accuracy relative to single-mode inversion. Preliminary field tests are performed using the new hybrid method, and the results are shown to support the conclusions of the numerical study and confirm the feasibility of the proposed technique. Although the use of multiple modes in surface wave testing is not new, the proposed hybrid method can provide more accurate and complete multimodal dispersion data than achieved with surface-only Rayleigh wave methods. As a result, errors because of misidentification or partial measurement of higher modes may be minimized, thus reducing statistical uncertainty in the

  17. Calcium-Vitamin D Co-supplementation Affects Metabolic Profiles, but not Pregnancy Outcomes, in Healthy Pregnant Women

    PubMed Central

    Asemi, Zatollah; Samimi, Mansooreh; Siavashani, Mehrnush Amiri; Mazloomi, Maryam; Tabassi, Zohreh; Karamali, Maryam; Jamilian, Mehri; Esmaillzadeh, Ahmad

    2016-01-01

    Background: Pregnancy is associated with unfavorable metabolic profile, which might in turn result in adverse pregnancy outcomes. The current study was designed to evaluate the effects of calcium plus Vitamin D administration on metabolic status and pregnancy outcomes in healthy pregnant women. Methods: This randomized double-blind placebo-controlled clinical trial was performed among 42 pregnant women aged 18–40 years who were at week 25 of gestation. Subjects were randomly allocated to consume either 500 mg calcium-200 IU cholecalciferol supplements (n = 21) or placebo (n = 21) for 9 weeks. Blood samples were obtained at the onset of the study and after 9-week trial to determine related markers. Post-delivery, the newborn's weight, length, and head circumference were measured during the first 24 h after birth. Results: Consumption of calcium-Vitamin D co-supplements resulted in a significant reduction of serum high-sensitivity C-reactive protein levels compared with placebo (−1856.8 ± 2657.7 vs. 707.1 ± 3139.4 μg/mL, P = 0.006). We also found a significant elevation of plasma total antioxidant capacity (89.3 ± 118.0 vs. −9.4 ± 164.9 mmol/L, P = 0.03), serum 25-hydroxyvitamin D (2.5 ± 3.5 vs. −1.7 ± 1.7 ng/mL, P < 0.0001), and calcium levels (0.6 ± 0.6 vs. −0.1 ± 0.4 mg/dL, P < 0.0001). The supplementation led to a significant decrease in diastolic blood pressure (−1.9 ± 8.3 vs. 3.1 ± 5.2 mmHg, P = 0.02) compared with placebo. No significant effect of calcium-Vitamin D co-supplements was seen on other metabolic profiles. We saw no significant change of the co-supplementation on pregnancy outcomes as well. Conclusions: Although calcium-Vitamin D co-supplementation for 9 weeks in pregnant women resulted in improved metabolic profiles, it did not affect pregnancy outcomes. PMID:27076887

  18. Lipoprotein particle subclass profiles among metabolically healthy and unhealthy obese and non-obese adults: does size matter?

    PubMed

    Phillips, Catherine M; Perry, Ivan J

    2015-10-01

    No data regards lipoprotein particle profiles in obese and non-obese metabolic health subtypes exist. We characterised lipoprotein size, particle and subclass concentrations among metabolically healthy and unhealthy obese and non-obese adults. Cross-sectional sample of 1834 middle-aged Irish adults were classified as obese (BMI ≥30 kg/m(2)) and non-obese (BMI <30 kg/m(2)). Metabolic health was defined using three metabolic health definitions based on various cardiometabolic abnormalities including metabolic syndrome criteria, insulin resistance and inflammation. Lipoprotein size, particle and subclass concentrations were determined using nuclear magnetic resonance (NMR) spectroscopy. Lipoprotein profiling identified a range of adverse phenotypes among the metabolically unhealthy individuals, regardless of BMI and metabolic health definition, including increased numbers of small low density lipoprotein (LDL) (P < 0.001) and high density lipoprotein (HDL) particles (P < 0.001), large very low density lipoprotein (VLDL) particles (P < 0.001) and greater lipoprotein related insulin resistance (P < 0.001). The most significant predictors of metabolic health were lower numbers of large VLDL (ORs 2.72-3.13 and 2.49-3.86, P < 0.05 among obese and non-obese individuals, respectively) and small dense LDL particles (ORs 1.78-2.39 and 1.50-1.94, P < 0.05) and higher numbers of large LDL (ORs 1.82-2.66 and 2.84-3.27, P < 0.05) and large HDL particles (ORs 1.88-2.58 and 1.81-3.49, P < 0.05). Metabolically healthy adults displayed favourable lipoprotein particle profiles, irrespective of BMI and metabolic health definition. These findings underscore the importance of maintaining a healthy lipid profile in the context of overall cardiometabolic health. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Effects of alpha-tocopherol on oxidative status and metabolic profile in overweight women.

    PubMed

    Ble-Castillo, J L; Cleva-Villanueva, G; Díaz-Zagoya, J C; Medina-Santillán, R; Rubio-Arias, H O; Méndez, J D

    2007-12-01

    Despite extensive research, the effects of alpha-tocopherol supplementation remain controversial. Few studies have been focused on obese and overweight people. We examined the effects of alpha-tocopherol (AT) on the oxidative status and metabolic profile in overweight women. Sixteen overweight women between the ages of 40-60 years old, received AT, 800 IU/day during 12 weeks, followed by a 6-week washout period. Blood samples were taken at the beginning and then every 6 weeks until the end of the study. AT, retinol, malondialdehyde (MDA), total antioxidant status (TAS), selenium-dependent glutathione peroxidase (GPx) and CuZn-superoxide dismutase (SOD) were quantified to evaluate the oxidative stress. The metabolic profile was estimated by measuring glycated hemoglobin (HbA1c) in erythrocytes and glucose, phosphate, magnesium, lipid and lipoprotein concentrations in serum. Under AT administration HbA1c, serum- MDA levels and erythrocyte GPx activity were markedly reduced. TAS, AT and Mg2+ concentrations in serum and SOD activity in erythrocytes were higher after AT treatment. Body weight; glucose, lipid and retinol concentrations, or blood cells count were unchanged. Lipid peroxidation was considerably reduced in AT treated women and also improved serum antioxidant status was observed, but the imbalanced response between erythrocyte SOD and GPx activities could affect normal response to oxidative stress.

  20. Effects of α-Tocopherol on Oxidative Status and Metabolic Profile in Overweight Women

    PubMed Central

    Ble-Castillo, J. L.; Cleva-Villanueva, G.; Díaz-Zagoya, J. C.; Medina-Santillán, R.; Rubio-Arias, H. O.; Méndez, J. D.

    2007-01-01

    Despite extensive research, the effects of α-tocopherol supplementation remain controversial. Few studies have been focused on obese and overweight people. We examined the effects of α-tocopherol (AT) on the oxidative status and metabolic profile in overweight women. Sixteen overweight women between the ages of 40–60 years old, received AT, 800 IU/day during 12 weeks, followed by a 6-week washout period. Blood samples were taken at the beginning and then every 6 weeks until the end of the study. AT, retinol, malondialdehyde (MDA), total antioxidant status (TAS), selenium-dependent glutathione peroxidase (GPx) and CuZn-superoxide dismutase (SOD) were quantified to evaluate the oxidative stress. The metabolic profile was estimated by measuring glycated hemoglobin (HbA1c) in erythrocytes and glucose, phosphate, magnesium, lipid and lipoprotein concentrations in serum. Under AT administration HbA1c, serum-MDA levels and erythrocyte GPx activity were markedly reduced. TAS, AT and Mg2+ concentrations in serum and SOD activity in erythrocytes were higher after AT treatment. Body weight; glucose, lipid and retinol concentrations, or blood cells count were unchanged. Lipid peroxidation was considerably reduced in AT treated women and also improved serum antioxidant status was observed, but the imbalanced response between erythrocyte SOD and GPx activities could affect normal response to oxidative stress. PMID:18180536

  1. Metabolic profiling of the protozoan parasite Entamoeba invadens revealed activation of unpredicted pathway during encystation.

    PubMed

    Jeelani, Ghulam; Sato, Dan; Husain, Afzal; Escueta-de Cadiz, Aleyla; Sugimoto, Masahiro; Soga, Tomoyoshi; Suematsu, Makoto; Nozaki, Tomoyoshi

    2012-01-01

    Encystation, which is cellular differentiation from the motile, proliferative, labile trophozoite form to the dormant, resistant cyst form, is a crucial process found in parasitic and free-living protozoa such as Entamoeba, Giardia, Acanthamoeba, and Balamuthia. Since encystation is an essential process to deal with the adverse external environmental changes during the life cycle, and often integral to the transmission of the diseases, biochemical understanding of the process potentially provides useful measures against the infections caused by this group of protozoa. In this study, we investigated metabolic and transcriptomic changes that occur during encystation in Entamoeba invadens, the reptilian sibling of mammal-infecting E. histolytica, using capillary electrophoresis-tandem mass spectrometry-based metabolite profiling and DNA microarray-based expression profiling. As the encystation progressed, the levels of majority of metabolites involved in glycolysis and nucleotides drastically decreased, indicating energy generation is ceased. Furthermore, the flux of glycolysis was redirected toward chitin wall biosynthesis. We found remarkable temporal increases in biogenic amines such as isoamylamine, isobutylamine, and cadaverine, during the early period of encystation, when the trophozoites form large multicellular aggregates (precyst). We also found remarkable induction of γ-aminobutyric acid (GABA) during encystation. This study has unveiled for the first time the dynamics of the transcriptional and metabolic regulatory networks during encystation, and should help in better understanding of the process in pathogenic eukaryotes, and further development of measures controlling infections they cause.

  2. Metabolic Profiling of the Protozoan Parasite Entamoeba invadens Revealed Activation of Unpredicted Pathway during Encystation

    PubMed Central

    Jeelani, Ghulam; Sato, Dan; Husain, Afzal; Escueta-de Cadiz, Aleyla; Sugimoto, Masahiro; Soga, Tomoyoshi; Suematsu, Makoto; Nozaki, Tomoyoshi

    2012-01-01

    Encystation, which is cellular differentiation from the motile, proliferative, labile trophozoite form to the dormant, resistant cyst form, is a crucial process found in parasitic and free-living protozoa such as Entamoeba, Giardia, Acanthamoeba, and Balamuthia. Since encystation is an essential process to deal with the adverse external environmental changes during the life cycle, and often integral to the transmission of the diseases, biochemical understanding of the process potentially provides useful measures against the infections caused by this group of protozoa. In this study, we investigated metabolic and transcriptomic changes that occur during encystation in Entamoeba invadens, the reptilian sibling of mammal-infecting E. histolytica, using capillary electrophoresis-tandem mass spectrometry-based metabolite profiling and DNA microarray-based expression profiling. As the encystation progressed, the levels of majority of metabolites involved in glycolysis and nucleotides drastically decreased, indicating energy generation is ceased. Furthermore, the flux of glycolysis was redirected toward chitin wall biosynthesis. We found remarkable temporal increases in biogenic amines such as isoamylamine, isobutylamine, and cadaverine, during the early period of encystation, when the trophozoites form large multicellular aggregates (precyst). We also found remarkable induction of γ-aminobutyric acid (GABA) during encystation. This study has unveiled for the first time the dynamics of the transcriptional and metabolic regulatory networks during encystation, and should help in better understanding of the process in pathogenic eukaryotes, and further development of measures controlling infections they cause. PMID:22662204

  3. Dietary live yeast alters metabolic profiles, protein biosynthesis and thermal stress tolerance of Drosophila melanogaster.

    PubMed

    Colinet, Hervé; Renault, David

    2014-04-01

    The impact of nutritional factors on insect's life-history traits such as reproduction and lifespan has been excessively examined; however, nutritional determinant of insect's thermal tolerance has not received a lot of attention. Dietary live yeast represents a prominent source of proteins and amino acids for laboratory-reared drosophilids. In this study, Drosophila melanogaster adults were fed on diets supplemented or not with live yeast. We hypothesized that manipulating nutritional conditions through live yeast supplementation would translate into altered physiology and stress tolerance. We verified how live yeast supplementation affected body mass characteristics, total lipids and proteins, metabolic profiles and cold tolerance (acute and chronic stress). Females fed with live yeast had increased body mass and contained more lipids and proteins. Using GC/MS profiling, we found distinct metabolic fingerprints according to nutritional conditions. Metabolite pathway enrichment analysis corroborated that live yeast supplementation was associated with amino acid and protein biosyntheses. The cold assays revealed that the presence of dietary live yeast greatly promoted cold tolerance. Hence, this study conclusively demonstrates a significant interaction between nutritional conditions and thermal tolerance.

  4. Perturbation in kidney lipid metabolic profiles in diabetic rats with reference to alcoholic oxidative stress

    PubMed Central

    Shanmugam, K. R.; Ramakrishna, C. H.; Mallikarjuna, K.; Reddy, K. Sathyavelu

    2009-01-01

    Diabetes is a major threat to global public health, and the number of diabetic patients is rapidly increasing worldwide. Evidence suggests that oxidative stress is involved in the pathophysiology of diabetic complications and alcoholic diseases. The aim of this study is to find out the impact of alcohol on lipid metabolic profiles in kidney tissue under streptozotocin induced diabetic condition. No study has been reported so far on the effect of alcohol on diabetic condition and also with reference to lipid metabolic profiles. Hence, the present study has been designed to elucidate the impact of alcoholism on diabetic condition. Male wistar strain albino rats were randomly divided into four groups: control (saline treated) NC, alcohol-treated (At), diabetic control (DC), and alcohol-treated diabetic rats (D+At). In alcohol-treated diabetic rats, we observed high levels of MDA, total cholesterol, triglycerides, phospholipids and also high levels of blood glucose than other groups. Moreover, degenerative changes of renal cells in alcohol-treated diabetic group were maximized by administration of alcohol as evinced by histopathological examination. This study suggests that alcohol consumption could be an aggravation factor which contributes for the formation of free radicals in diabetic condition. Therefore, consumption of alcohol during diabetic condition is harmful. PMID:20436729

  5. The relationship between blood pressure, anthropometric indices and metabolic profile in adolescents: a cross sectional study.

    PubMed

    Dalili, Setila; Mohammadi, Hamid; Rezvany, Seyed Mahmood; Dadashi, Arsalan; Novin, Mohammad Hassan; Gholaminejad, Hajar; Medghalchi, Abdolreza; Mohtasham Amiri, Zahra; Dalili, Hossein; Hassanzadeh Rad, Afagh

    2015-05-01

    To investigate the relationship between blood pressure, anthropometric indices and metabolic profile in adolescents. The present cross sectional study was conducted in 1005, 12-y-old junior students referred to 15 urban health centers of Rasht. Samples were recruited randomly and data were collected in a form which consisted of demographic characteristics, history of disease in samples and their immediate families, birth weight, physical examination and clinical examination including height, weight, blood pressure and body mass index. Also, metabolic profiles including fasting blood sugar (FBS), blood sugar (BS), cholesterol, and triglyceride (TG), low density lipoprotein (LDL), high-density lipoprotein (HDL) and insulin levels were measured. Data were analyzed in SPSS software, by descriptive and analytic statistics and p value 0.05 was considered statistically significant. Eight hundred fifty nine adolescents consisting of 550 (64 %) boys and 309 (34 %) girls participated in this study; 11.4 % (84/739 cases) of the participants had hypertension. The strongest correlation was seen between systolic blood pressure and weight, waist or hip circumferences and insulin levels. Also, FBS had very weak correlation with blood pressure. Thus, weight, waist and hip circumferences, insulin levels, high TG and low HDL have been indicated as the strongest correlating factors for high blood pressure.Thus, these factors should be investigated in high risk children and followed in hypertensive child to monitor cardiometabolic risk factors.

  6. Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum.

    PubMed

    Beisser, Daniela; Grohme, Markus A; Kopka, Joachim; Frohme, Marcus; Schill, Ralph O; Hengherr, Steffen; Dandekar, Thomas; Klau, Gunnar W; Dittrich, Marcus; Müller, Tobias

    2012-06-19

    Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress. In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurable metabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source

  7. Noninvasive Metabolic Profiling using Microfluidics for Analysis of Single Preimplantation Embryos

    PubMed Central

    Urbanski, John Paul; Johnson, Mark T.; Craig, David D.; Potter, David L.; Gardner, David K.; Thorsen, Todd

    2010-01-01

    Noninvasive analysis of metabolism at the single cell level will have many applications in evaluating cellular physiology. One clinically relevant application would be to determine the metabolic activities of embryos produced through assisted reproduction. There is increasing evidence that embryos with greater developmental capacity have distinct metabolic profiles. One of the standard techniques for evaluating embryonic metabolism has been to evaluate consumption and production of several key energetic substrates (glucose, pyruvate and lactate) using microfluorometric enzymatic assays. These assays are performed manually using constriction pipettes, which greatly limits the utility of this system. Through multilayer soft-lithography, we have designed a microfluidic device that can perform these assays in an automated fashion. Following manual loading of samples and enzyme cocktail reagents, this system performs sample and enzyme cocktail aliquotting, mixing of reagents, data acquisition and data analysis without operator intervention. Optimization of design and operating regimens has resulted in the ability to perform serial measurements of glucose, pyruvate and lactate in triplicate with sub-microliter sample volumes within 5 minutes. The current architecture allows for automated analysis of 10 samples and intermittent calibration over a three hour period. Standard curves generated for each metabolite have correlation coefficients that routinely exceed 0.99. Using a standard epifluorescent microscope and CCD camera, linearity is obtained with metabolite concentrations in the low micromolar range (low femtomoles of total analyte). This system is inherently flexible, being easily adapted for any NAD(P)H-based assay and scaled up in terms of sample ports. Open source JAVA-based software allows for simple alterations in routine algorithms. Furthermore, this device can be used as a standalone device in which media samples are loaded or be integrated into microfluidic

  8. Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum

    PubMed Central

    2012-01-01

    Background Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress. Results In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurable metabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and

  9. Comparative metabolic profiling of mce1 operon mutant vs wild-type Mycobacterium tuberculosis strains.

    PubMed

    Queiroz, Adriano; Medina-Cleghorn, Daniel; Marjanovic, Olivera; Nomura, Daniel K; Riley, Lee W

    2015-11-01

    Mycobacterium tuberculosis disrupted in a 13-gene operon (mce1) accumulates free mycolic acids (FM) in its cell wall and causes accelerated death in mice. Here, to more comprehensively analyze differences in their cell wall lipid composition, we used an untargeted metabolomics approach to compare the lipid profiles of wild-type and mce1 operon mutant strains. By liquid chromatography-mass spectrometry, we identified >400 distinct lipids significantly altered in the mce1 mutant compared to wild type. These lipids included decreased levels of saccharolipids and glycerophospholipids, and increased levels of alpha-, methoxy- and keto mycolic acids (MA), and hydroxyphthioceranic acid. The mutant showed reduced expression of mmpL8, mmpL10, stf0, pks2 and papA2 genes involved in transport and metabolism of lipids recognized to induce proinflammatory response; these lipids were found to be decreased in the mutant. In contrast, the transcripts of mmpL3, fasI, kasA, kasB, acpM and RV3451 involved in MA transport and metabolism increased; MA inhibits inflammatory response in macrophages. Since the mce1 operon is known to be regulated in intracellular M. tuberculosis, we speculate that the differences we observed in cell wall lipid metabolism and composition may affect host response to M. tuberculosis infection and determine the clinical outcome of such an infection. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life.

    PubMed

    Pinola, Pekka; Puukka, Katri; Piltonen, Terhi T; Puurunen, Johanna; Vanky, Eszter; Sundström-Poromaa, Inger; Stener-Victorin, Elisabet; Lindén Hirschberg, Angelica; Ravn, Pernille; Skovsager Andersen, Marianne; Glintborg, Dorte; Mellembakken, Jan Roar; Ruokonen, Aimo; Tapanainen, Juha S; Morin-Papunen, Laure C

    2017-03-01

    To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Case-control study. Not applicable. In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: <30, 30-39, and >39 years). None. Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two- to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  11. Metabolite profiling reveals clear metabolic changes during somatic embryo development of Norway spruce (Picea abies).

    PubMed

    Businge, Edward; Brackmann, Klaus; Moritz, Thomas; Egertsdotter, Ulrika

    2012-02-01

    Progress on industrial-scale propagation of conifers by somatic embryogenesis has been hampered by the differences in developmental capabilities between cell lines, which are limiting the capture of genetic gains from breeding programs. In this study, we investigated the metabolic events occurring during somatic embryo development in Norway spruce to establish a better understanding of the fundamental metabolic events required for somatic embryo development. Three embryogenic cell lines of Norway spruce (Picea abies (L.) Karst) with different developmental capabilities were studied during somatic embryo development from proliferation of proembryogenic masses to mature somatic embryos. The three different cell lines displayed normal, aberrant and blocked somatic embryo development. Metabolite profiles from four development stages in each of the cell lines were obtained using combined gas chromatography-mass spectrometry. Multivariate discriminant analyses of the metabolic data revealed significant metabolites (P  ≤  0.05) for each development stage and transition. The results suggest that endogenous auxin and sugar signaling affects initial stages of somatic embryo development. Furthermore, the results highlight the importance of a timed stress response and the presence of stimulatory metabolites during late stages of embryo development.

  12. Tissue metabolic profiling of lymph node metastasis of colorectal cancer assessed by 1H NMR.

    PubMed

    Zhang, Hailong; Qiao, Liang; Li, Xiaopeng; Wan, Yang; Yang, Li; Wang, Huijuan

    2016-12-01

    Lymph node metastasis is a decisive prognostic and therapeutic staging factor for colorectal cancer (CRC), which is one of the most prevalent types of cancer and a malignant tumor. The metabolic profiling of tissue samples from a large cohort of lymph node non‑metastatic CRC patients (n=73), lymph node metastatic CRC patients (n=52) and normal controls (n=41) was performed using 1H nuclear magnetic resonance (NMR) together with multivariate statistical analyses. Excellent separation was obtained between CRC patients and normal controls, and CRC patients were also perfectly classified according to lymph node metastasis. Forty‑two distinguishing metabolites were identified, which revealed disturbance of glycolysis, glutaminolysis, fatty acid metabolism, choline metabolism and amino acids, suggesting that cellular functions in energy production, macromolecular synthesis, oxidative stress and immune escape of cancer cells are affected in CRC. In total, 10 tissue metabolites were significantly disturbed between non‑metastatic and metastatic CRC patients. The present study firstly staged CRC patients by lymph node metastasis by metabolomic approach. The identified metabolites may be associated with the neoplasia, invasion and metastasis of the tumor. The results suggest the promising application of these metabolites in clinical therapy, and further understanding of the related mechanism warrants further investigation.

  13. Maternal chromium restriction modulates miRNA profiles related to lipid metabolism disorder in mice offspring.

    PubMed

    Zhang, Qian; Xiao, Xinhua; Zheng, Jia; Li, Ming; Yu, Miao; Ping, Fan; Wang, Zhixin; Qi, Cuijuan; Wang, Tong; Wang, Xiaojing

    2017-08-01

    Increasing evidence shows that maternal nutrition status has a vital effect on offspring susceptibility to obesity. MicroRNAs are related to lipid metabolism processes. This study aimed to evaluate whether maternal chromium restriction could affect miRNA expression involved in lipid metabolism in offspring. Weaning C57BL/6J mice born from mothers fed with normal control diet or chromium-restricted diet were fed for 13 weeks. The adipose miRNA expression profile was analyzed by miRNA array analysis. At 16 weeks old, pups from dams fed with chromium-restricted diet exhibit higher body weight, fat weight, and serum TC, TG levels. Six miRNAs were identified as upregulated in the RC group compared with the CC group, whereas eight miRNAs were lower than the threshold level set in the RC group. In the validated target genes of these differentially expressed miRNA, the MAPK signaling pathway serves an important role in the influence of early life chromium-restricted diet on lipid metabolism through miRNA. Long-term programming on various specific miRNA and MAPK signaling pathway may be involved in maternal chromium restriction in the adipose of female offspring. Impact statement For the first time, our study demonstrates important miRNA differences in the effect of maternal chromium restriction in offspring. These miRNAs may serve as "bridges" between the mother and the offspring by affecting the MAPK pathway.

  14. Growth and metabolic profiling of the novel thermophilic bacterium Thermoanaerobacter sp. strain YS13.

    PubMed

    Peng, Tingting; Pan, Siyi; Christopher, Lew P; Sparling, Richard; Levin, David B

    2016-09-01

    A strictly anaerobic, thermophilic bacterium, designated strain YS13, was isolated from a geothermal hot spring. Phylogenetic analysis using the 16S rRNA genes and cpn60 UT genes suggested strain YS13 as a species of Thermoanaerobacter. Using cellobiose or xylose as carbon source, YS13 was able to grow over a wide range of temperatures (45-70 °C), and pHs (pH 5.0-9.0), with optimum growth at 65 °C and pH 7.0. Metabolic profiling on cellobiose, glucose, or xylose in 1191 medium showed that H2, CO2, ethanol, acetate, and lactate were the major metabolites. Lactate was the predominant end product from glucose or cellobiose fermentations, whereas H2 and acetate were the dominant end products from xylose fermentation. The metabolic balance shifted away from ethanol to H2, acetate, and lactate when YS13 was grown on cellobiose as temperatures increased from 45 to 70 °C. When YS13 was grown on xylose, a metabolic shift from lactate to H2, CO2, and acetate was observed in cultures as the temperature of incubation increased from 45 to 65 °C, whereas a shift from ethanol and CO2 to H2, acetate, and lactate was observed in cultures incubated at 70 °C.

  15. Profiling of Cytosolic and Peroxisomal Acetyl-CoA Metabolism in Saccharomyces cerevisiae

    PubMed Central

    Chen, Yun; Siewers, Verena; Nielsen, Jens

    2012-01-01

    As a key intracellular metabolite, acetyl-coenzyme A (acetyl-CoA) plays a major role in various metabolic pathways that link anabolism and catabolism. In the yeast Saccharomyces cerevisiae, acetyl-CoA involving metabolism is compartmentalized, and may vary with the nutrient supply of a cell. Membranes separating intracellular compartments are impermeable to acetyl-CoA and no direct transport between the compartments occurs. Thus, without carnitine supply the glyoxylate shunt is the sole possible route for transferring acetyl-CoA from the cytosol or the peroxisomes into the mitochondria. Here, we investigate the physiological profiling of different deletion mutants of ACS1, ACS2, CIT2 and MLS1 individually or in combination under alternative carbon sources, and study how various mutations alter carbon distribution. Based on our results a detailed model of carbon distribution about cytosolic and peroxisomal acetyl-CoA metabolism in yeast is suggested. This will be useful to further develop yeast as a cell factory for the biosynthesis of acetyl-CoA-derived products. PMID:22876324

  16. Smoothed Profile Method to Simulate Colloidal Particles in Complex Fluids

    NASA Astrophysics Data System (ADS)

    Yamamoto, Ryoichi; Nakayama, Yasuya; Kim, Kang

    A new direct numerical simulation scheme, called "Smoothed Profile (SP) method," is presented. The SP method, as a direct numerical simulation of particulate flow, provides a way to couple continuum fluid dynamics with rigid-body dynamics through smoothed profile of colloidal particle. Our formulation includes extensions to colloids in multicomponent solvents such as charged colloids in electrolyte solutions. This method enables us to compute the time evolutions of colloidal particles, ions, and host fluids simultaneously by solving Newton, advection-diffusion, and Navier-Stokes equations so that the electro-hydrodynamic couplings can be fully taken into account. The electrophoretic mobilities of charged spherical particles are calculated in several situations. The comparisons with approximation theories show quantitative agreements for dilute dispersions without any empirical parameters.

  17. Metabolic profiling of polycystic ovary syndrome reveals interactions with abdominal obesity.

    PubMed

    Couto Alves, A; Valcarcel, B; Mäkinen, V-P; Morin-Papunen, L; Sebert, S; Kangas, A J; Soininen, P; Das, S; De Iorio, M; Coin, L; Ala-Korpela, M; Järvelin, M-R; Franks, S

    2017-09-01

    Polycystic ovary syndrome (PCOS) is a common reproductive disorder associated with metabolic disturbances including obesity, insulin resistance and diabetes mellitus. Here we investigate whether changes in the metabolic profile of PCOS women are driven by increased tendency to obesity or are specific features of PCOS related to increased testosterone levels. We conducted an NMR metabolomics association study of PCOS cases (n=145) and controls (n=687) nested in a population-based birth cohort (n=3127). Subjects were 31 years old at examination. The main analyses were adjusted for waist circumference (WC) as a proxy measure of central obesity. Subsequently, metabolite concentrations were compared between cases and controls within pre-defined WC strata. In each stratum, additional metabolomics association analyses with testosterone levels were conducted separately among cases and controls. Overall, women with PCOS showed more adverse metabolite profiles than the controls. Four lipid fractions in different subclasses of very low density lipoprotein (VLDL) were associated with PCOS, after adjusting for WC and correction for multiple testing (P<0.002). In stratified analysis the PCOS women within large WC strata (⩾98 cm) had significantly lower high density lipoprotein (HDL) levels, Apo A1 and albumin values compared with the controls. Testosterone levels were significantly associated with VLDL and serum lipids in PCOS cases with large WC but not in the controls. The higher testosterone levels, adjusted for WC, associated adversely with insulin levels and HOMA IR in cases but not in the controls. Our findings show that both abdominal obesity and hyperandrogenism contribute to the dyslipidaemia and other metabolic traits of PCOS which all may negatively contribute to the long-term health of women with PCOS.

  18. Body composition and metabolic profile in women with complete androgen insensitivity syndrome.

    PubMed

    Dati, E; Baroncelli, G I; Mora, S; Russo, G; Baldinotti, F; Parrini, D; Erba, P; Simi, P; Bertelloni, S

    2009-01-01

    Clinical and experimental data suggest that androgen receptor (AR) signaling plays a role on body composition, glucose homeostasis and lipid metabolism. The effect of AR disruption on such parameters was not extensively investigated in human people. A group of young to middle-age adult women with complete androgen insensitivity syndrome (CAIS, n = 18, age 32.2 +/- 9.3 years; women with testes removed n = 14) was investigated for body mass index (BMI), body composition (dual energy X-ray absorptiometry), serum glucose levels, insulin sensitivity (HOMA-IR) and lipid profile. Mean BMI (24.2 +/- 7.4 kg/m(2)) was not significantly increased (T-score 1.0 +/- 2.5, p = NS vs Italian female reference values), but prevalence of obesity was higher in women with CAIS than that reported in age-related Italian females (16.7% vs 3.6%, respectively). The majority of obese individuals with CAIS was in the subgroup with intact testes (3/4). DXA assessment (n = 15) demonstrated values of total free fat mass similar to that of 46,XX female controls. Increased body fat was found in CAIS women in comparison with both female and male controls. Abnormal values of cholesterol (total and LDL) and HOMA-IR were present in a large subset of patients. Our data suggest that in women with CAIS disruption of AR signaling may increase body fat and affect some metabolic parameters. Assessment of body composition, metabolic profile and, likely, cardiovascular risk seems to be advisable with ageing in these individuals.

  19. Kidney Tissue Targeted Metabolic Profiling of Unilateral Ureteral Obstruction Rats by NMR

    PubMed Central

    Li, Zhenyu; Li, Aiping; Gao, Jining; Li, Hong; Qin, Xuemei

    2016-01-01

    Renal interstitial fibrosis is a common pathological process in the progression of kidney disease. A nuclear magnetic resonance (NMR) based metabolomic approach was used to analyze the kidney tissues of rats with renal interstitial fibrosis (RIF), induced by unilateral ureteral obstruction (UUO). The combination of a variety of statistical methods were used to screen out 14 significantly changed potential metabolites, which are related with multiple biochemical processes including amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress. The exploration of the contralateral kidneys enhanced the understanding of the disease, which was also supported by serum biochemistry and kidney histopathology results. In addition, the pathological parameters (clinical chemistry, histological and immunohistochemistry results) were correlated with the significantly changed differential metabolites related with RIF. This study showed that targeted tissue metabolomic analysis can be used as a useful tool to understand the mechanism of the disease and provide a novel insight in the pathogenesis of RIF. PMID:27695416

  20. Turbulence profiling methods applied to ESO's adaptive optics facility

    NASA Astrophysics Data System (ADS)

    Valenzuela, Javier; Béchet, Clémentine; Garcia-Rissmann, Aurea; Gonté, Frédéric; Kolb, Johann; Le Louarn, Miska; Neichel, Benoît; Madec, Pierre-Yves; Guesalaga, Andrés.

    2014-07-01

    Two algorithms were recently studied for C2n profiling from wide-field Adaptive Optics (AO) measurements on GeMS (Gemini Multi-Conjugate AO system). They both rely on the Slope Detection and Ranging (SLODAR) approach, using spatial covariances of the measurements issued from various wavefront sensors. The first algorithm estimates the C2n profile by applying the truncated least-squares inverse of a matrix modeling the response of slopes covariances to various turbulent layer heights. In the second method, the profile is estimated by deconvolution of these spatial cross-covariances of slopes. We compare these methods in the new configuration of ESO Adaptive Optics Facility (AOF), a high-order multiple laser system under integration. For this, we use measurements simulated by the AO cluster of ESO. The impact of the measurement noise and of the outer scale of the atmospheric turbulence is analyzed. The important influence of the outer scale on the results leads to the development of a new step for outer scale fitting included in each algorithm. This increases the reliability and robustness of the turbulence strength and profile estimations.

  1. The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers.

    PubMed

    Paula, Pierozan; Fredrik, Jernerén; Yusuf, Ransome; Oskar, Karlsson

    2017-02-28

    The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO2 inhalation, and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO2 inhalation and decapitation. CO2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods are critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. This article is protected by copyright. All rights reserved.

  2. Efficient finite element method for grating profile reconstruction

    NASA Astrophysics Data System (ADS)

    Zhang, Ruming; Sun, Jiguang

    2015-12-01

    This paper concerns the reconstruction of grating profiles from scattering data. The inverse problem is formulated as an optimization problem with a regularization term. We devise an efficient finite element method (FEM) and employ a quasi-Newton method to solve it. For the direct problems, the FEM stiff and mass matrices are assembled once at the beginning of the numerical procedure. Then only minor changes are made to the mass matrix at each iteration, which significantly saves the computation cost. Numerical examples show that the method is effective and robust.

  3. Hepatic drug metabolizing profile of Flinders Sensitive Line rat model of depression.

    PubMed

    Kotsovolou, Olga; Ingelman-Sundberg, Magnus; Lang, Matti A; Marselos, Marios; Overstreet, David H; Papadopoulou-Daifoti, Zoi; Johanson, Inger; Fotopoulos, Andrew; Konstandi, Maria

    2010-08-16

    The Flinders Sensitive Line (FSL) rat model of depression exhibits some behavioral, neurochemical, and pharmacological features that have been reported in depressed patients and has been very effective in screening antidepressants. Major factor that determines the effectiveness and toxicity of a drug is the drug metabolizing capacity of the liver. Therefore, in order to discriminate possible differentiation in the hepatic drug metabolism between FSL rats and Sprague-Dawley (SD) controls, their hepatic metabolic profile was investigated in this study. The data showed decreased glutathione (GSH) content and glutathione S-transferase (GST) activity and lower expression of certain major CYP enzymes, including the CYP2B1, CYP2C11 and CYP2D1 in FSL rats compared to SD controls. In contrast, p-nitrophenol hydroxylase (PNP), 7-ethoxyresorufin-O-dealkylase (EROD) and 16alpha-testosterone hydroxylase activities were higher in FSL rats. Interestingly, the wide spread environmental pollutant benzo(alpha)pyrene (B(alpha)P) induced CYP1A1, CYP1A2, CYP2B1/2 and ALDH3c at a lesser extend in FSL than in SD rats, whereas the antidepressant mirtazapine (MIRT) up-regulated CYP1A1/2, CYP2C11, CYP2D1, CYP2E1 and CYP3A1/2, mainly, in FSL rats. The drug also further increased ALDH3c whereas suppressed GSH content in B(alpha)P-exposed FSL rats. In conclusion, several key enzymes of the hepatic biotransformation machinery are differentially expressed in FSL than in SD rats, a condition that may influence the outcome of drug therapy. The MIRT-induced up-regulation of several drug-metabolizing enzymes indicates the critical role of antidepressant treatment that should be always taken into account in the designing of treatment and interpretation of insufficient pharmacotherapy or drug toxicity.

  4. Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats.

    PubMed

    Allaway, David; Gilham, Matthew S; Colyer, Alison; Jönsson, Thomas J; Swanson, Kelly S; Morris, Penelope J

    2016-01-01

    Neutering is a significant risk factor for obesity in cats. The mechanisms that promote neuter-associated weight gain are not well understood but following neutering, acute changes in energy expenditure and energy consumption have been observed. Metabolic profiling (GC-MS and UHPLC-MS-MS) was used in a longitudinal study to identify changes associated with age, sexual development and neutering in male cats fed a nutritionally-complete dry diet to maintain an ideal body condition score. At eight time points, between 19 and 52 weeks of age, fasted blood samples were taken from kittens neutered at either 19 weeks of age (Early Neuter (EN), n = 8) or at 31 weeks of age (Conventional Neuter (CN), n = 7). Univariate and multivariate analyses were used to compare plasma metabolites (n = 370) from EN and CN cats. Age was the primary driver of variance in the plasma metabolome, including a developmental change independent of neuter group between 19 and 21 weeks in lysolipids and fatty acid amides. Changes associated with sexual development and its subsequent loss were also observed, with differences at some time points observed between EN and CN cats for 45 metabolites (FDR p<0.05). Pathway Enrichment Analysis also identified significant effects in 20 pathways, dominated by amino acid, sterol and fatty acid metabolism. Most changes were interpretable within the context of male sexual development, and changed following neutering in the CN group. Felinine metabolism in CN cats was the most significantly altered pathway, increasing during sexual development and decreasing acutely following neutering. Felinine is a testosterone-regulated, felid-specific glutathione derivative secreted in urine. Alterations in tryptophan, histidine and tocopherol metabolism observed in peripubertal cats may be to support physiological functions of glutathione following diversion of S-amino acids for urinary felinine secretion.

  5. Comprehensive Analysis of PPARα-Dependent Regulation of Hepatic Lipid Metabolism by Expression Profiling

    PubMed Central

    Rakhshandehroo, Maryam; Sanderson, Linda M.; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; de Groot, Philip J.; Müller, Michael; Kersten, Sander

    2007-01-01

    PPARα is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARα in hepatic lipid metabolism, many PPARα-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARα-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARα target genes, livers from several animal studies in which PPARα was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARα-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARα-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein β polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARα agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARα. Our study illustrates the power of transcriptional profiling to uncover novel PPARα-regulated genes and pathways in liver. PMID:18288265

  6. Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.

    PubMed

    Rakhshandehroo, Maryam; Sanderson, Linda M; Matilainen, Merja; Stienstra, Rinke; Carlberg, Carsten; de Groot, Philip J; Müller, Michael; Kersten, Sander

    2007-01-01

    PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARalpha-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARalpha target genes, livers from several animal studies in which PPARalpha was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARalpha-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARalpha-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein beta polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARalpha agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARalpha. Our study illustrates the power of transcriptional profiling to uncover novel PPARalpha-regulated genes and pathways in liver.

  7. Profiles of the biosynthesis and metabolism of pyridine nucleotides in potatoes (Solanum tuberosum L.).

    PubMed

    Katahira, Riko; Ashihara, Hiroshi

    2009-12-01

    As part of a research program on nucleotide metabolism in potato tubers (Solanum tuberosum L.), profiles of pyridine (nicotinamide) metabolism were examined based on the in situ metabolic fate of radio-labelled precursors and the in vitro activities of enzymes. In potato tubers, [(3)H]quinolinic acid, which is an intermediate of de novo pyridine nucleotide synthesis, and [(14)C]nicotinamide, a catabolite of NAD, were utilised for pyridine nucleotide synthesis. The in situ tracer experiments and in vitro enzyme assays suggest the operation of multiple pyridine nucleotide cycles. In addition to the previously proposed cycle consisting of seven metabolites, we found a new cycle that includes newly discovered nicotinamide riboside deaminase which is also functional in potato tubers. This cycle bypasses nicotinamide and nicotinic acid; it is NAD --> nicotinamide mononucleotide --> nicotinamide riboside --> nicotinic acid riboside --> nicotinic acid mononucleotide --> nicotinic acid adenine dinucleotide --> NAD. Degradation of the pyridine ring was extremely low in potato tubers. Nicotinic acid glucoside is formed from nicotinic acid in potato tubers. Comparative studies of [carboxyl-(14)C]nicotinic acid metabolism indicate that nicotinic acid is converted to nicotinic acid glucoside in all organs of potato plants. Trigonelline synthesis from [carboxyl-(14)C]nicotinic acid was also found. Conversion was greater in green parts of plants, such as leaves and stem, than in underground parts of potato plants. Nicotinic acid utilised for the biosynthesis of these conjugates seems to be derived not only from the pyridine nucleotide cycle, but also from the de novo synthesis of nicotinic acid mononucleotide.

  8. Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats

    PubMed Central

    Allaway, David; Gilham, Matthew S.; Colyer, Alison; Jönsson, Thomas J.; Swanson, Kelly S.; Morris, Penelope J.

    2016-01-01

    Neutering is a significant risk factor for obesity in cats. The mechanisms that promote neuter-associated weight gain are not well understood but following neutering, acute changes in energy expenditure and energy consumption have been observed. Metabolic profiling (GC-MS and UHPLC-MS-MS) was used in a longitudinal study to identify changes associated with age, sexual development and neutering in male cats fed a nutritionally-complete dry diet to maintain an ideal body condition score. At eight time points, between 19 and 52 weeks of age, fasted blood samples were taken from kittens neutered at either 19 weeks of age (Early Neuter (EN), n = 8) or at 31 weeks of age (Conventional Neuter (CN), n = 7). Univariate and multivariate analyses were used to compare plasma metabolites (n = 370) from EN and CN cats. Age was the primary driver of variance in the plasma metabolome, including a developmental change independent of neuter group between 19 and 21 weeks in lysolipids and fatty acid amides. Changes associated with sexual development and its subsequent loss were also observed, with differences at some time points observed between EN and CN cats for 45 metabolites (FDR p<0.05). Pathway Enrichment Analysis also identified significant effects in 20 pathways, dominated by amino acid, sterol and fatty acid metabolism. Most changes were interpretable within the context of male sexual development, and changed following neutering in the CN group. Felinine metabolism in CN cats was the most significantly altered pathway, increasing during sexual development and decreasing acutely following neutering. Felinine is a testosterone-regulated, felid-specific glutathione derivative secreted in urine. Alterations in tryptophan, histidine and tocopherol metabolism observed in peripubertal cats may be to support physiological functions of glutathione following diversion of S-amino acids for urinary felinine secretion. PMID:27942045

  9. Changes in metabolic profiles during acute kidney injury and recovery following ischemia/reperfusion.

    PubMed

    Wei, Qingqing; Xiao, Xiao; Fogle, Paul; Dong, Zheng

    2014-01-01

    Changes of metabolism have been implicated in renal ischemia/reperfusion injury (IRI). However, a global analysis of the metabolic changes in renal IRI is lacking and the association of the changes with ischemic kidney injury and subsequent recovery are unclear. In this study, mice were subjected to 25 minutes of bilateral renal IRI followed by 2 hours to 7 days of reperfusion. Kidney injury and subsequent recovery was verified by serum creatinine and blood urea nitrogen measurements. The metabolome of plasma, kidney cortex, and medulla were profiled by the newly developed global metabolomics analysis. Renal IRI induced overall changes of the metabolome in plasma and kidney tissues. The changes started in renal cortex, followed by medulla and plasma. In addition, we identified specific metabolites that may contribute to early renal injury response, perturbed energy metabolism, impaired purine metabolism, impacted osmotic regulation and the induction of inflammation. Some metabolites, such as 3-indoxyl sulfate, were induced at the earliest time point of renal IRI, suggesting the potential of being used as diagnostic biomarkers. There was a notable switch of energy source from glucose to lipids, implicating the importance of appropriate nutrition supply during treatment. In addition, we detected the depressed polyols for osmotic regulation which may contribute to the loss of kidney function. Several pathways involved in inflammation regulation were also induced. Finally, there was a late induction of prostaglandins, suggesting their possible involvement in kidney recovery. In conclusion, this study demonstrates significant changes of metabolome kidney tissues and plasma in renal IRI. The changes in specific metabolites are associated with and may contribute to early injury, shift of energy source, inflammation, and late phase kidney recovery.

  10. Metabolic Profiling of Geobacter sulfurreducens during Industrial Bioprocess Scale-Up.

    PubMed

    Muhamadali, Howbeer; Xu, Yun; Ellis, David I; Allwood, J William; Rattray, Nicholas J W; Correa, Elon; Alrabiah, Haitham; Lloyd, Jonathan R; Goodacre, Royston

    2015-05-15

    During the industrial scale-up of bioprocesses it is important to establish that the biological system has not changed significantly when moving from small laboratory-scale shake flasks or culturing bottles to an industrially relevant production level. Therefore, during upscaling of biomass production for a range of metal transformations, including the production of biogenic magnetite nanoparticles by Geobacter sulfurreducens, from 100-ml bench-scale to 5-liter fermentors, we applied Fourier transform infrared (FTIR) spectroscopy as a metabolic fingerprinting approach followed by the analysis of bacterial cell extracts by gas chromatography-mass spectrometry (GC-MS) for metabolic profiling. FTIR results clearly differentiated between the phenotypic changes associated with different growth phases as well as the two culturing conditions. Furthermore, the clustering patterns displayed by multivariate analysis were in agreement with the turbidimetric measurements, which displayed an extended lag phase for cells grown in a 5-liter bioreactor (24 h) compared to those grown in 100-ml serum bottles (6 h). GC-MS analysis of the cell extracts demonstrated an overall accumulation of fumarate during the lag phase under both culturing conditions, coinciding with the detected concentrations of oxaloacetate, pyruvate, nicotinamide, and glycerol-3-phosphate being at their lowest levels compared to other growth phases. These metabolites were overlaid onto a metabolic network of G. sulfurreducens, and taking into account the levels of these metabolites throughout the fermentation process, the limited availability of oxaloacetate and nicotinamide would seem to be the main metabolic bottleneck resulting from this scale-up process. Additional metabolite-feeding experiments were carried out to validate the above hypothesis. Nicotinamide supplementation (1 mM) did not display any significant effects on the lag phase of G. sulfurreducens cells grown in the 100-ml serum bottles. However

  11. Metabolite profiling of Phycomyces blakesleeanus carotene mutants reveals global changes across intermediary metabolism.

    PubMed

    Alcalde, Eugenio; Fraser, Paul David

    2016-11-01

    The filamentous fungus Phycomyces blakesleeanus provides a renewable biosource of industrial high-value compounds such as carotenes, other isoprenoids (ubiquinone and sterols), organic acids and fatty acids. Several Phycomyces mutants involved in the formation of β-carotene are available. For example, the carA mutants have a leaky mutation in the phytoene synthase and produce significantly lower amounts of carotenes, while the carB and carR mutants produce phytoene and lycopene, respectively, due to a null mutation in the genes encoding the phytoene dehydrogenase and lycopene cyclase, respectively. The carS mutants are mutated in the gene encoding the oxygenase responsible for the conversion of β-carotene into apocarotenoids and, as a result, β-carotene accumulates. In order to ascertain further the biochemical changes arising in these potential industrial strains, a metabolite profiling workflow was implemented for Phycomyces. GC-MS and ultra-performance liquid chromatography-photodiode array platforms enabled the identification of over 100 metabolites in 11 carA, carB, carR and carS mutant strains and their wild-type comparator. All mutant strains possessed decreased TCA cycle intermediates, galactose, alanine and ribitol, while dodecanol and valine showed a general increase. As predicted, other terpenoid levels were affected in the carB, carR and carS mutants but not in the carA mutants. The global changes across intermediary metabolism of the mutants suggest that complex metabolic networks exist between intermediary and secondary metabolism or that other mutations beyond the carotene pathway may exist in these mutants. These data show the utility of the methodology in metabolically phenotyping Phycomyces strains with potential industrial exploitation.

  12. Metabolic profile study of 7, 8-dihydroxyflavone in monkey plasma using high performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Sun, Taoping; Chen, Sijing; Huang, Hao; Li, Tianqing; Yang, Wei; Liu, Liegang

    2017-09-01

    7, 8-Dihydroxyflavone, as a high-affinity tropomyosin-receptor-kinase B agonist, can mimic the physiological actions of brain-derived neurotrophic factor and exert a variety of neurological actions in numerous models including Parkinsońs disease, depression, learning and memory. Nonetheless, a limited number of studies have been focused on its metabolism in mammal and no methodology has been reported for the determination of 7, 8-DHF and its metabolites. Herein, we developed a rapid, sensitive and accurate method using high performance liquid chromatography-tandem mass spectroscopy for the determination of 7, 8-DHF and its metabolites in monkey plasma. The lower limits of quantification for analytes were 0.4-2.0ngmL(-1). The intra-day and inter-day precisions (relative standard deviation, %) of analytes were within 11.83%, and the accuracy (relative error, %) ranged from -6.86 to 14.00%. The mean extraction recoveries for analytes were more than 89.14%. This validated method was successfully applied to the metabolic profile study of 7, 8-DHF in monkey plasma. The results indicated that 7, 8-DHF undergoes methylation, glucuronidation and/or sulfation, and the conjugated forms are the main metabolites in monkey plasma. We further demonstrated that methylated 7, 8-DHF can be also conjugated with glucuronidation/sulfation, and the methylation occurs mainly in the 8 position. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Association of circulating irisin levels with metabolic and metabolite profiles of Korean adolescents.

    PubMed

    Jang, Han Byul; Kim, Hyo-Jin; Kang, Jae Heon; Park, Sang Ick; Park, Kyung Hee; Lee, Hye-Ja

    2017-08-01

    Irisin, a novel exercise-induced myokine, has been suggested to regulate energy metabolism. We studied the relationship between circulating irisin and metabolic and metabolite profiles of Korean adolescents, and investigated the effects of physical activity, obesity, and metabolic syndrome (MetS) on irisin levels. Data were obtained from the Korean Children-Adolescents Study. Our cross-sectional study included 618 adolescents (370 normal-weight and 248 obese adolescents; 316 boys and 302 girls) aged 12-15years. Body composition was determined using an impedance body composition analyzer and general participant characteristics and lifestyle information were obtained from questionnaires. Serum irisin levels were measured using a commercial kit. Mean body mass index (BMI) was 19.4kg/m(2) in normal-weight adolescents and 31.4kg/m(2) in obese adolescents. Circulating irisin was positively correlated with adiposity indices, including BMI z-score, waist circumference, percent body fat, fat mass, fat-free mass, fat mass to fat-free mass ratio, and lipid and glucose metabolism markers, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, glucose, insulin, and homeostasis model assessment-estimated insulin resistance (all p≤0.006). Of these, increased body fat mass [standardized (Std) ß, 0.23; p<0.0001], LDL-C (Std ß, 0.14; p=0.0005) and fasting glucose (Std ß, 0.08; p=0.0383) were the main independent factors associated with higher irisin levels. Moreover, elevated serum irisin was associated with the risk of obesity [odds ratio (OR], 2.2; confidence interval (CI), 1.19-3.87] and MetS (OR, 2.0; CI, 1.15-3.47). Furthermore, irisin and branched-chain amino acids were positively associated (p<4×10(-4) for Bonferroni correction). Additionally, in the normal-weight group, girls had higher irisin levels than boys (p=0.006) and adolescents who engaged in regular physical activity had higher levels of irisin than sedentary adolescents (p=0

  14. Graphical method for profiling hob mill that generate cycloid worms

    NASA Astrophysics Data System (ADS)

    Teodor, V.; Berbinschi, S.; Baroiu, N.; Oancea, N.

    2015-11-01

    The hob mill for generating ordered curls of cycloid surface with non involute profiles may be profiled based on the fundamental theorems of surface enveloping - Olivier - as surface reciprocally enveloping with point like contact. In this paper, is proposed a methodology based on a complementary theorem of the surface enveloping in a graphical expression developed in a graphical design environment - CATIA. The graphical method presented in this paper is developed in two stages: determining of the rack gear model based on the solid model of the surface to be generated, using an original algorithm, following this, based on 3D modelling is determined the solid model of the primary peripheral surface of the hob mill. An application for a cycloid worm is presented - a central screw of helical pumps. In order to prove the quality of method, the analytical and graphical solutions are comparatively presented.

  15. An improved method for profile radiography of piping

    SciTech Connect

    Bell, M.S.; Haupt, J.D.

    1996-07-01

    The Petro-Chemical industry has used profile radiography for more than thirty years to find, and evaluate, corrosion in piping systems. The technique offers a method of ``seeing into`` a piece of pipe. This allows the inspector to see the ``whole picture``. Single point ultrasonic measurements cannot provide this degree of information. Shell`s objective for studying the use of this method centered on optimizing their profile radiography technique to improve accuracy and reproducibility of wall thickness measurements. Accuracy and reproducibility of measurements are particularly important when used to determine corrosion rates. To help achieve this objective, the authors developed an inspection procedure to minimize the more prominent sources of inaccuracies associated with this technique. Along with this procedure, they also developed an associated training program. All of Shell Oil`s Pressure Equipment inspectors and key contract employees have received this training.

  16. MProfiler: A Profile-Based Method for DNA Motif Discovery

    NASA Astrophysics Data System (ADS)

    Altarawy, Doaa; Ismail, Mohamed A.; Ghanem, Sahar M.

    Motif Finding is one of the most important tasks in gene regulation which is essential in understanding biological cell functions. Based on recent studies, the performance of current motif finders is not satisfactory. A number of ensemble methods have been proposed to enhance the accuracy of the results. Existing ensemble methods overall performance is better than stand-alone motif finders. A recent ensemble method, MotifVoter, significantly outperforms all existing stand-alone and ensemble methods. In this paper, we propose a method, MProfiler, to increase the accuracy of MotifVoter without increasing the run time by introducing an idea called center profiling. Our experiments show improvement in the quality of generated clusters over MotifVoter in both accuracy and cluster compactness. Using 56 datasets, the accuracy of the final results using our method achieves 80% improvement in correlation coefficient nCC, and 93% improvement in performance coefficient nPC over MotifVoter.

  17. Methods for verifying the accuracy of wind profiles

    NASA Technical Reports Server (NTRS)

    Strauch, R. C.

    1986-01-01

    Comparisons of radar-measured winds have been made with several types of measurements not only to verify radar data but also to seek a satisfactory comparison method. Three of the comparisons that have been made with Colorado Profiler radars are summarized. Radar measurements were compared with radiosonde measurements. Infrared lidar and 915 MHz radar were compared with radiosondes. A brief radar/radar comparison was made using the 50-MHz radar and a 3-cm wavelength meteorological Doppler radar during precipitation.

  18. Metabolic Profiling Provides a System Understanding of Hypothyroidism in Rats and Its Application

    PubMed Central

    Dong, Xin; Zhu, Zhenyu; Li, Wuhong; Lou, Ziyang; Chai, Yifeng

    2013-01-01

    Background Hypothyroidism is a chronic condition of endocrine disorder and its precise molecular mechanism remains obscure. In spite of certain efficacy of thyroid hormone replacement therapy in treating hypothyroidism, it often results in other side effects because of its over-replacement, so it is still urgent to discover new modes of treatment for hypothyroidism. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against hypothyroidism. However, its holistic effect assessment and mechanistic understanding are still lacking due to its complex components. Methodology/Principal Findings A urinary metabonomic method based on ultra performance liquid chromatography coupled to mass spectrometry was employed to explore global metabolic characters of hypothyroidism. Three typical hypothyroidism models (methimazole-, propylthiouracil- and thyroidectomy-induced hypothyroidism) were applied to elucidate the molecular mechanism of hypothyroidism. 17, 21, 19 potential biomarkers were identified with these three hypothyroidism models respectively, primarily involved in energy metabolism, amino acid metabolism, sphingolipid metabolism and purine metabolism. In order to avert the interference of drug interaction between the antithyroid drugs and SND, the thyroidectomy-induced hypothyroidism model was further used to systematically assess the therapeutic efficacy of SND on hypothyroidism. A time-dependent recovery tendency was observed in SND-treated group from the beginning of model to the end of treatment, suggesting that SND exerted a recovery effect on hypothyroidism in a time-dependent manner through partially regulating the perturbed metabolic pathways. Conclusions/Significance Our results showed that the metabonomic approach is instrumental to understand the pathophysiology of hypothyroidism and offers a valuable tool for systematically studying the therapeutic effects of SND on hypothyroidism. PMID

  19. Sleeve Gastrectomy Reduces Body Weight and Improves Metabolic Profile also in Obesity-Prone Rats.

    PubMed

    Moncada, Rafael; Becerril, Sara; Rodríguez, Amaia; Méndez-Giménez, Leire; Ramírez, Beatriz; Catalán, Victoria; Gómez-Ambrosi, Javier; Gil, M Jesús; Fernández, Secundino; Cienfuegos, Javier A; Valentí, Víctor; Frühbeck, Gema

    2016-07-01

    Susceptibility to obesity is associated with a notable inter-individual variation. The aim of the present study was to compare the effectiveness of sleeve gastrectomy (SG) on weight loss and metabolic profile in obesity-prone (OP) rats vs animals that are non-susceptible to obesity (NSO). Young male Wistar rats (n = 101) were put in a diet-induced obesity (DIO) programme with ad libitum access to a high-fed diet (HFD) during 12 months. Body weight and food intake were regularly registered. Thereafter, rats were ranked by final body weight to identify the obesity-prone (OP) (n = 13) and non-susceptible to obesity (NSO) (n = 14) animals. OP and NSO rats were submitted to surgical interventions (sham operation, SG and pair-fed to the amount of food eaten by sleeve-gastrectomized rats). Body weight, food intake, energy expenditure, body temperature, fat pads weight, and metabolic profiling were analysed 4 weeks after surgical or dietary interventions. SG in both OP and NSO rats decreased body weight as compared to sham and pair-fed groups (P < 0.05), mainly due to reductions in subcutaneous and perirenal fat mass (P < 0.001). Total weight loss achieved in sleeve-gastrectomized OP and NSO rats was higher than that of pair-fed ones (P < 0.05), showing that the SG effect goes beyond caloric restriction. In this regard, sleeve-gastrectomized rats exhibited significantly (P < 0.05) increased basal rectal temperature together with upregulated brown adipose tissue Ucp-1 protein expression levels. A significant (P < 0.05) improvement in insulin sensitivity was also observed in both OP and NSO animals that underwent SG as compared with pair-fed counterparts. Our findings provide the first evidence that obesity-prone rats also benefit from surgery responding effectively to SG, as evidenced by the significant body weight reduction and the metabolic profile improvement.

  20. Effects of phototherapy plus physical training on metabolic profile and quality of life in postmenopausal women.

    PubMed

    Paolillo, Fernanda Rossi; Borghi-Silva, Audrey; Arena, Ross; Parizotto, Nivaldo Antonio; Kurachi, Cristina; Bagnato, Vanderlei Salvador

    2017-10-01

    A cluster of metabolic abnormalities are markedly higher among postmenopausal women. The present study evaluated the effects of infrared light