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Sample records for nmr-based metabonomic analysis

  1. Automics: an integrated platform for NMR-based metabonomics spectral processing and data analysis.

    Science.gov (United States)

    Wang, Tao; Shao, Kang; Chu, Qinying; Ren, Yanfei; Mu, Yiming; Qu, Lijia; He, Jie; Jin, Changwen; Xia, Bin

    2009-03-16

    Spectral processing and post-experimental data analysis are the major tasks in NMR-based metabonomics studies. While there are commercial and free licensed software tools available to assist these tasks, researchers usually have to use multiple software packages for their studies because software packages generally focus on specific tasks. It would be beneficial to have a highly integrated platform, in which these tasks can be completed within one package. Moreover, with open source architecture, newly proposed algorithms or methods for spectral processing and data analysis can be implemented much more easily and accessed freely by the public. In this paper, we report an open source software tool, Automics, which is specifically designed for NMR-based metabonomics studies. Automics is a highly integrated platform that provides functions covering almost all the stages of NMR-based metabonomics studies. Automics provides high throughput automatic modules with most recently proposed algorithms and powerful manual modules for 1D NMR spectral processing. In addition to spectral processing functions, powerful features for data organization, data pre-processing, and data analysis have been implemented. Nine statistical methods can be applied to analyses including: feature selection (Fisher's criterion), data reduction (PCA, LDA, ULDA), unsupervised clustering (K-Mean) and supervised regression and classification (PLS/PLS-DA, KNN, SIMCA, SVM). Moreover, Automics has a user-friendly graphical interface for visualizing NMR spectra and data analysis results. The functional ability of Automics is demonstrated with an analysis of a type 2 diabetes metabolic profile. Automics facilitates high throughput 1D NMR spectral processing and high dimensional data analysis for NMR-based metabonomics applications. Using Automics, users can complete spectral processing and data analysis within one software package in most cases. Moreover, with its open source architecture, interested

  2. Automics: an integrated platform for NMR-based metabonomics spectral processing and data analysis

    Directory of Open Access Journals (Sweden)

    Qu Lijia

    2009-03-01

    Full Text Available Abstract Background Spectral processing and post-experimental data analysis are the major tasks in NMR-based metabonomics studies. While there are commercial and free licensed software tools available to assist these tasks, researchers usually have to use multiple software packages for their studies because software packages generally focus on specific tasks. It would be beneficial to have a highly integrated platform, in which these tasks can be completed within one package. Moreover, with open source architecture, newly proposed algorithms or methods for spectral processing and data analysis can be implemented much more easily and accessed freely by the public. Results In this paper, we report an open source software tool, Automics, which is specifically designed for NMR-based metabonomics studies. Automics is a highly integrated platform that provides functions covering almost all the stages of NMR-based metabonomics studies. Automics provides high throughput automatic modules with most recently proposed algorithms and powerful manual modules for 1D NMR spectral processing. In addition to spectral processing functions, powerful features for data organization, data pre-processing, and data analysis have been implemented. Nine statistical methods can be applied to analyses including: feature selection (Fisher's criterion, data reduction (PCA, LDA, ULDA, unsupervised clustering (K-Mean and supervised regression and classification (PLS/PLS-DA, KNN, SIMCA, SVM. Moreover, Automics has a user-friendly graphical interface for visualizing NMR spectra and data analysis results. The functional ability of Automics is demonstrated with an analysis of a type 2 diabetes metabolic profile. Conclusion Automics facilitates high throughput 1D NMR spectral processing and high dimensional data analysis for NMR-based metabonomics applications. Using Automics, users can complete spectral processing and data analysis within one software package in most cases

  3. NMR-based metabonomic analysis of MnO-embedded iron oxide nanoparticles as potential dual-modal contrast agents

    Science.gov (United States)

    Li, Jinquan; Zhou, Zijian; Feng, Jianghua; Cai, Shuhui; Gao, Jinhao; Chen, Zhong

    2014-05-01

    MnO-embedded iron oxide nanoparticles (MnIO-NPs) can be treated as potential dual-modal contrast agents. However, their overall bio-effects and potential toxicity remain unknown. In this study, the metabolic effects of MnIO-NPs (dosed at 1 and 5 mg Fe/kg) on Sprague-Dawley rats were investigated using metabonomic analysis, histopathological examination, and conventional biochemical analysis. The histological changes included a focal inflammation in the liver at high-dose and a slightly enlarged area of splenic white pulp after 48 h post-dose. Blood biochemical analysis showed that albumin, globulins, aspartate aminotransferase, lactate dehydrogenase, blood urea nitrogen, and glucose changed distinctly compared to the control. The metabonomic analysis of body fluids (serum and urine) and tissues (liver, kidney, and spleen) indicated that MnIO-NPs induced metabolic perturbation in rats including energy, nucleotides, amino acids and phospholipid metabolisms. Besides, the variations of supportive nutrients: valine, leucine, isoleucine, nicotinamide adenine dinucleotide (phosphate), and nicotinamide, and the conjugation substrates: glycine, taurine, glutamine, glutathione, and methyl donors (formate, sarcosine, dimethylglycine, choline, and betaine) were involved in detoxification reaction of MnIO-NPs. The obtained information would provide identifiable ground for the candidate selection and optimization.

  4. Effect of magnetic field strength on NMR-based metabonomic human urine data. Comparative study of 250, 400, 500, and 800 MHz

    DEFF Research Database (Denmark)

    Bertram, Hanne Christine; Malmendal, Anders; Petersen, Bent O.

    2007-01-01

    Metabonomic analysis of urine utilizing high-resolution NMR spectroscopy and chemometric techniques has proven valuable in characterizing the biochemical response to an intervention. To assess the effect of magnetic field strength on information contained in NMR-based metabonomic data sets, 1H NMR...

  5. Ehrlich and sarcoma 180 tumour characterisation and early detection by {sup 1}H NMR-based metabonomics of mice serum

    Energy Technology Data Exchange (ETDEWEB)

    Grandizoli, Caroline W.P. da S.; Simonelli, Fabio; Nagata, Noemi; Barison, Andersson, E-mail: andernmr@ufpr.br [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Quimica; Carrenho, Luise Z.B.; Francisco, Thais M.G. de; Campos, Francinete R. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Farmacia; Santana Filho, Arquimedes P. de; Sassaki, Guilherme L. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Dept. de Bioquimica; Kreuger, Maria R.O. [Universidade do Vale do Itajai (UNIVALI), (Brazil). Centro de Ciencias da Saude

    2014-05-15

    The success of cancer treatment is directly related to early detection before symptoms emerge, although nowadays few cancers can be detected early. In this sense, {sup 1}H nuclear magnetic resonance ({sup 1}H NMR)-based metabonomics was used to identify metabolic changes in biofluid as a consequence of tumours growing in mice. Through partial least squares discriminant analysis (PLS-DA) analysis of {sup 1}H NMR spectra from serum samples it was possible to diagnose Ehrlich ascites and Sarcoma 180 tumours five and ten days after cell inoculation, respectively. Lipids, lipoproteins and lactate were the main biomarkers at onset as well as in the progress of carcinogenic process. Thus, NMR-based metabonomics can be a valuable tool to study the effects of tumour establishment on the chemical composition of biofluids. (author)

  6. Ischemic stroke progress evaluation by {sup 31}P NMR-based metabonomic of human serum

    Energy Technology Data Exchange (ETDEWEB)

    Grandizoli, Caroline W.P.S.; Barison, Andersson, E-mail: andernmr@ufpr.br [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Departamento de Quimica. Centro de RMN; Lange, Marcos C.; Novak, Felipe T. M. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital de Clínicas. Divisao de Neurologia; Campos, Francinete R. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Departmento de Farmacia

    2014-07-01

    In this work, chemometric analyses over {sup 31}P{"1"H} NMR (nuclear magnetic resonance) spectra of human blood serum permitted to discriminated ischemic stroke patients from health individuals due to changes in the chemical composition of phosphorus-containing compounds. These results indicate that {sup 31}P NMR-based metabonomic allowed insights over the mechanism triggered by ischemic stroke. (author)

  7. NMR-Based Metabonomic Investigation of Heat Stress in Myotubes Reveals a Time-Dependent Change in the Metabolites

    DEFF Research Database (Denmark)

    Straadt, Ida K; Young, Jette F; Bross, Peter

    2010-01-01

    NMR-based metabonomics was applied to elucidate the time-dependent stress responses in mouse myotubes after heat exposure of either 42 or 45 degrees C for 1 h. Principal component analysis (PCA) revealed that the gradual time-dependent changes in metabolites contributing to the clustering...... and separation of the control samples from the different time points after heat stress primarily are in the metabolites glucose, leucine, lysine, phenylalanine, creatine, glutamine, and acetate. In addition, PC scores revealed a maximum change in metabolite composition 4 h after the stress exposure; thereafter......, samples returned toward control samples, however, without reaching the control samples even 10 h after stress. The results also indicate that the myotubes efficiently regulate the pH level by release of lactate to the culture medium at a heat stress level of 42 degrees C, which is a temperature level...

  8. NMR-based metabonomics reveals that plasma betaine increases upon intake of high-fiber rye buns in hypercholesterolemic pigs

    DEFF Research Database (Denmark)

    Bertram, Hanne Christine S.; Malmendal, Anders; Nielsen, Niels Chr

    2009-01-01

    fiber for 9-10 wk. Fasting plasma samples were collected 2 days before and after 8 and 12 days on the experimental diets, while postprandial samples taken after 58-67 days, and( 1)H NMR spectra were acquired on these. Principal component analysis on the obtained NMR spectra demonstrated clear effects...... in this region. The 3.29 ppm signal is ascribed to N(CH(3))(3) protons in betaine, which may be an important contributor to the health promoting effects of rye.......This study presents an NMR-based metabonomic approach to explore the overall endogenous biochemical effects of a rye versus wheat-based fiber-rich diet in hypercholesterolemic pigs. The pigs were fed high-fat, high-cholesterol rye- (n = 9) or wheat- (n = 8) based buns with similar levels of dietary...

  9. NMR-based metabonomic approach on the toxicological effects of a Cimicifuga triterpenoid.

    Science.gov (United States)

    He, Cui-Cui; Dai, Yun-Qing; Hui, Rong-Rong; Hua, Jia; Chen, Hong-Juan; Luo, Qiao-Yun; Li, Jian-Xin

    2012-02-01

    Cimicifugae Rhizoma, a well-known botanical dietary supplement, has been the subject of intense interest due to its potential application for alleviating menopausal symptom. Although there are clinic data that the Cimicifuga extract should have hepatotoxicity, no evidence on the main chemical components has been reported. Cimicidol-3-O-β -d-xyloside (CX) is one of the main triterpenoids of the rhizome. This work studies the toxicological effects of CX after oral administration (50 mg kg(-1) per day) over a 7-day period in female SD rats using metabonomic analyses of (1) H NMR spectra of urine, serum and liver tissue extracts. Histopathological studies of liver and analyses of blood biochemical parameter, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine revealed that CX had no negative impacts on liver and kidney. However, the metabolic signature of (1) H NMR-based urinalysis of daily samples displayed an increment in the levels of taurine, trimethylamine-N-oxide (TMAO), betaine and acetate. Elevated serum levels of creatinine, glucose, alanine, TMAO and betaine and lower levels of lactate were observed. Metabolic profiling on aqueous soluble extracts of liver showed simultaneously increases in succinate, glycogen, choline, glycerophosphorylcholine, TMAO and betaine levels and reduction in valine, glucose and lactate levels. Nevertheless, no changes in any metabonomic level were found in lipid-soluble extracts of liver. These findings indicate that CX has a slight toxicity in liver and kidney via disturbance of the metabolisms of energy and amino acids. The present study provides a reasonable explanation for the clinical hepatotoxicity of Cimicifuga extract. Copyright © 2011 John Wiley & Sons, Ltd.

  10. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Science.gov (United States)

    Bu, Qian; Yan, Guangyan; Deng, Pengchi; Peng, Feng; Lin, Hongjun; Xu, Youzhi; Cao, Zhixing; Zhou, Tian; Xue, Aiqin; Wang, Yanli; Cen, Xiaobo; Zhao, Ying-Lan

    2010-03-01

    As titanium dioxide nanoparticles (TiO2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO2 NPs (dosed at 0.16, 0.4 and 1 g kg - 1, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  11. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    International Nuclear Information System (INIS)

    Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan; Yan Guangyan; Cen Xiaobo; Deng Pengchi; Peng Feng; Xue Aiqin; Wang Yanli

    2010-01-01

    As titanium dioxide nanoparticles (TiO 2 NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO 2 NPs (dosed at 0.16, 0.4 and 1 g kg -1 , respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by 1 H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO 2 NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, α-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO 2 NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO 2 NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO 2 NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  12. NMR-based metabonomic study of the sub-acute toxicity of titanium dioxide nanoparticles in rats after oral administration

    Energy Technology Data Exchange (ETDEWEB)

    Bu Qian; Lin Hongjun; Xu Youzhi; Cao Zhixing; Zhou Tian; Zhao Yinglan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Yan Guangyan; Cen Xiaobo [National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Deng Pengchi [Analytical and Testing Center, Sichuan University, Chengdu 610041 (China); Peng Feng [Department of Thoracic Oncology of Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Xue Aiqin [Institute of Bioengineering, Zhejiang Sci-Tech University Road 2, Xiasha, Hangzhou 310018 (China); Wang Yanli, E-mail: alancenxb@sina.com [Tianjin Children' s Hospital, Tianjin 300074 (China)

    2010-03-26

    As titanium dioxide nanoparticles (TiO{sub 2} NPs) are widely used commercially, their potential toxicity on human health has attracted particular attention. In the present study, the oral toxicological effects of TiO{sub 2} NPs (dosed at 0.16, 0.4 and 1 g kg{sup -1}, respectively) were investigated using conventional approaches and metabonomic analysis in Wistar rats. Serum chemistry, hematology and histopathology examinations were performed. The urine and serum were investigated by {sup 1}H nuclear magnetic resonance (NMR) using principal components and partial least squares discriminant analysis. The metabolic signature of urinalysis in TiO{sub 2} NP-treated rats showed increases in the levels of taurine, citrate, hippurate, histidine, trimethylamine-N-oxide (TMAO), citrulline, {alpha}-ketoglutarate, phenylacetylglycine (PAG) and acetate; moreover, decreases in the levels of lactate, betaine, methionine, threonine, pyruvate, 3-D-hydroxybutyrate (3-D-HB), choline and leucine were observed. The metabonomics analysis of serum showed increases in TMAO, choline, creatine, phosphocholine and 3-D-HB as well as decreases in glutamine, pyruvate, glutamate, acetoacetate, glutathione and methionine after TiO{sub 2} NP treatment. Aspartate aminotransferase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) were elevated and mitochondrial swelling in heart tissue was observed in TiO{sub 2} NP-treated rats. These findings indicate that disturbances in energy and amino acid metabolism and the gut microflora environment may be attributable to the slight injury to the liver and heart caused by TiO{sub 2} NPs. Moreover, the NMR-based metabolomic approach is a reliable and sensitive method to study the biochemical effects of nanomaterials.

  13. A (1H NMR-Based Metabonomic Investigation of Time-Related Metabolic Trajectories of the Plasma, Urine and Liver Extracts of Hyperlipidemic Hamsters.

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    Chun-Ying Jiang

    Full Text Available The hamster has been previously found to be a suitable model to study the changes associated with diet-induced hyperlipidemia in humans. Traditionally, studies of hyperlipidemia utilize serum- or plasma-based biochemical assays and histopathological evaluation. However, unbiased metabonomic technologies have the potential to identify novel biomarkers of disease. Thus, to obtain a better understanding of the progression of hyperlipidemia and discover potential biomarkers, we have used a proton nuclear magnetic resonance spectroscopy ((1H-NMR-based metabonomics approach to study the metabolic changes occurring in the plasma, urine and liver extracts of hamsters fed a high-fat/high-cholesterol diet. Samples were collected at different time points during the progression of hyperlipidemia, and individual proton NMR spectra were visually and statistically assessed using two multivariate analyses (MVA: principal component analysis (PCA and orthogonal partial least squares-discriminant analysis (OPLS-DA. Using the commercial software package Chenomx NMR suite, 40 endogenous metabolites in the plasma, 80 in the urine and 60 in the water-soluble fraction of liver extracts were quantified. NMR analysis of all samples showed a time-dependent transition from a physiological to a pathophysiological state during the progression of hyperlipidemia. Analysis of the identified biomarkers of hyperlipidemia suggests that significant perturbations of lipid and amino acid metabolism, as well as inflammation, oxidative stress and changes in gut microbiota metabolites, occurred following cholesterol overloading. The results of this study substantially broaden the metabonomic coverage of hyperlipidemia, enhance our understanding of the mechanism of hyperlipidemia and demonstrate the effectiveness of the NMR-based metabonomics approach to study a complex disease.

  14. NMR-based metabonomic studies reveal changes in the biochemical profile of plasma and urine from pigs fed high fibre rye bread

    DEFF Research Database (Denmark)

    Bertram, Hanne C.; Bach Knudsen, Knud E.; Serena, Anja

    2006-01-01

    This study presents an NMR-based metabonomic approach to elucidate the overall endogenous biochemical effects of a wholegrain diet. Two diets with similar levels of dietary fibre and macronutrients, but with contrasting levels of wholegrain ingredients, were prepared from wholegrain rye (wholegrain...... diet (WGD)) and non-wholegrain wheat (non-wholegrain diet (NWD)) and fed to four pigs in a crossover design. Plasma samples were collected after 7 d on each diet, and 1H NMR spectra were acquired on these. Partial least squares regression discriminant analysis (PLS-DA) on spectra obtained for plasma...

  15. Organ-Specific Differential NMR-Based Metabonomic Analysis of Soybean [Glycine max (L. Merr.] Fruit Reveals the Metabolic Shifts and Potential Protection Mechanisms Involved in Field Mold Infection

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    Wen-yu Yang

    2017-04-01

    Full Text Available Prolonged, continuous rainfall is the main climatic characteristic of autumn in Southwest China, and it has been found to cause mildew outbreaks in pre-harvest soybean fields. Low temperature and humidity (LTH stress during soybean maturation in the field promotes pre-harvest mildew, resulting in damage to different organs of soybean fruits to different extents, but relatively little information on the resistance mechanisms in these fruits is available. Therefore, to understand the metabolic responses of soybean fruits to field mold (FM, the metabonomic variations induced by LTH were characterized using proton nuclear magnetic resonance spectroscopy (1H-NMR, and the primary metabolites from the pod, seed coat and cotyledon of pre-harvest soybean were quantified. Analysis of FM-damaged soybean germplasms with different degrees of resistance to FM showed that extracts were dominated by 66 primary metabolites, including amino acids, organic acids and sugars. Each tissue had a characteristic metabolic profile, indicating that the metabolism of proline in the cotyledon, lysine in the seed coat, and sulfur in the pod play important roles in FM resistance. The primary-secondary metabolism interface and its potential contribution to FM resistance was investigated by targeted analyses of secondary metabolites. Both the seed coat and the pod have distinct but nonexclusive metabolic responses to FM, and these are functionally integrated into FM resistance mechanisms.

  16. NMR-based metabonomic studies reveal changes in the biochemical profile of plasma and urine from pigs fed high-fibre rye bread

    DEFF Research Database (Denmark)

    Bertram, Hanne C; Bach Knudsen, Knud E; Serena, Anja

    2006-01-01

    This study presents an NMR-based metabonomic approach to elucidate the overall endogenous biochemical effects of a wholegrain diet. Two diets with similar levels of dietary fibre and macronutrients, but with contrasting levels of wholegrain ingredients, were prepared from wholegrain rye (wholegra...

  17. NMR-based metabonomic studies reveal changes in the biochemical profile of plasma and urine from pigs fed high-fibre rye bread

    DEFF Research Database (Denmark)

    Bertram, Hanne C; Bach Knudsen, Knud E; Serena, Anja

    2006-01-01

    This study presents an NMR-based metabonomic approach to elucidate the overall endogenous biochemical effects of a wholegrain diet. Two diets with similar levels of dietary fibre and macronutrients, but with contrasting levels of wholegrain ingredients, were prepared from wholegrain rye (wholegrain...... disclosed biochemical effects of a wholegrain diet on plasma betaine content and excretion of betaine and creatinine....

  18. Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry, histopathology and NMR-based metabonomic approach.

    Science.gov (United States)

    Benourad, Fouzia; Kahvecioglu, Zehra; Youcef-Benkada, Mokhtar; Colet, Jean-Marie

    2014-10-01

    In the field of natural extracts, research generally focuses on the study of their biological activities for food, cosmetic, or pharmacological purposes. The evaluation of their adverse effects is often overlooked. In this study, the extracts of Thymus vulgaris L. were obtained by two different extraction methods. Intraperitoneal injections of both extracts were given daily for four days to male Wistar Han rats, at two different doses for each extract. The evaluation of the potential toxic effects included histopathological examination of liver, kidney, and lung tissues, as well as serum biochemistry of liver and kidney parameters, and (1)H-NMR-based metabonomic profiles of urine. The results showed that no histopathological changes were observed in the liver and kidney in rats treated with both extracts of thyme. Serum biochemical investigations revealed significant increases in blood urea nitrogen, creatinine, and uric acid in animals treated with polyphenolic extract at both doses. In these latter groups, metabonomic analysis revealed alterations in a number of urine metabolites involved in the energy metabolism in liver mitochondria. Indeed, the results showed alterations of glycolysis, Krebs cycle, and β-oxidative pathways as evidenced by increases in lactate and ketone bodies, and decreases in citrate, α-ketoglutarate, creatinine, hippurate, dimethylglycine, and dimethyalanine. In conclusion, this work showed that i.p. injection of repeated doses of thyme extracts causes some disturbances of intermediary metabolism in rats. The metabonomic study revealed interesting data which could be further used to determine the cellular pathways affected by such treatments. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Metabonomics

    DEFF Research Database (Denmark)

    Bjerrum, Jacob T

    2015-01-01

    Without any prior knowledge, it can be an overwhelming task to get an overview of and insight into the field of metabonomics. This chapter introduces the concept of metabonomics, the most commonly applied techniques, and the inevitably indispensable multivariate statistical analyses in an easily...

  20. The serum metabolite response to diet intervention with probiotic acidified milk in irritable bowel syndrome patients is indistinguishable from that of non-probiotic acidified milk by 1H NMR-based metabonomic analysis

    DEFF Research Database (Denmark)

    Pedersen, Simon Metz; Nielsen, Niels Chr; Andersen, Henrik J

    2010-01-01

    The effects of a probiotic acidified milk product on the blood serum metabolite profile of patients suffering from Irritable Bowel Syndrome (IBS) compared to a non-probiotic acidified milk product was investigated using (1)H NMR metabonomics. For eight weeks, IBS patients consumed 0.4 L per day...... of a probiotic fermented milk product or non-probiotic acidified milk. Both diets resulted in elevated levels of blood serum L-lactate and 3-hydroxybutyrate. Our results showed identical effects of acidified milk consumption independent of probiotic addition. A similar result was previously obtained...

  1. A novel R-package graphic user interface for the analysis of metabonomic profiles

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    Villa Palmira

    2009-10-01

    Full Text Available Abstract Background Analysis of the plethora of metabolites found in the NMR spectra of biological fluids or tissues requires data complexity to be simplified. We present a graphical user interface (GUI for NMR-based metabonomic analysis. The "Metabonomic Package" has been developed for metabonomics research as open-source software and uses the R statistical libraries. Results The package offers the following options: Raw 1-dimensional spectra processing: phase, baseline correction and normalization. Importing processed spectra. Including/excluding spectral ranges, optional binning and bucketing, detection and alignment of peaks. Sorting of metabolites based on their ability to discriminate, metabolite selection, and outlier identification. Multivariate unsupervised analysis: principal components analysis (PCA. Multivariate supervised analysis: partial least squares (PLS, linear discriminant analysis (LDA, k-nearest neighbor classification. Neural networks. Visualization and overlapping of spectra. Plot values of the chemical shift position for different samples. Furthermore, the "Metabonomic" GUI includes a console to enable other kinds of analyses and to take advantage of all R statistical tools. Conclusion We made complex multivariate analysis user-friendly for both experienced and novice users, which could help to expand the use of NMR-based metabonomics.

  2. A novel R-package graphic user interface for the analysis of metabonomic profiles.

    Science.gov (United States)

    Izquierdo-García, Jose L; Rodríguez, Ignacio; Kyriazis, Angelos; Villa, Palmira; Barreiro, Pilar; Desco, Manuel; Ruiz-Cabello, Jesús

    2009-10-29

    Analysis of the plethora of metabolites found in the NMR spectra of biological fluids or tissues requires data complexity to be simplified. We present a graphical user interface (GUI) for NMR-based metabonomic analysis. The "Metabonomic Package" has been developed for metabonomics research as open-source software and uses the R statistical libraries. The package offers the following options: Raw 1-dimensional spectra processing: phase, baseline correction and normalization. Importing processed spectra. Including/excluding spectral ranges, optional binning and bucketing, detection and alignment of peaks. Sorting of metabolites based on their ability to discriminate, metabolite selection, and outlier identification. Multivariate unsupervised analysis: principal components analysis (PCA). Multivariate supervised analysis: partial least squares (PLS), linear discriminant analysis (LDA), k-nearest neighbor classification. Neural networks.Visualization and overlapping of spectra. Plot values of the chemical shift position for different samples. Furthermore, the "Metabonomic" GUI includes a console to enable other kinds of analyses and to take advantage of all R statistical tools. We made complex multivariate analysis user-friendly for both experienced and novice users, which could help to expand the use of NMR-based metabonomics.

  3. The Serum Metabolite Response to Diet Intervention with Probiotic Acidified Milk in Irritable Bowel Syndrome Patients Is Indistinguishable from that of Non-Probiotic Acidified Milk by 1H NMR-Based Metabonomic Analysis

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    Ulla Svensson

    2010-11-01

    Full Text Available The effects of a probiotic acidified milk product on the blood serum metabolite profile of patients suffering from Irritable Bowel Syndrome (IBS compared to a non-probiotic acidified milk product was investigated using 1H NMR metabonomics. For eight weeks, IBS patients consumed 0.4 L per day of a probiotic fermented milk product or non-probiotic acidified milk. Both diets resulted in elevated levels of blood serum l-lactate and 3-hydroxybutyrate. Our results showed identical effects of acidified milk consumption independent of probiotic addition. A similar result was previously obtained in a questionnaire-based evaluation of symptom relief. A specific probiotic effect is thus absent both in the patient subjective symptom evaluations and at the blood serum metabolite level. However, there was no correspondence between symptom relief and metabolite response on the patient level.

  4. Metabolic profiling of kidney and urine in rats with lithium-induced nephrogenic diabetes insipidus by (1)H-NMR-based metabonomics.

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    Hwang, Geum-Sook; Yang, Ji-Young; Ryu, Do Hyun; Kwon, Tae-Hwan

    2010-02-01

    Lithium (Li) treatment for bipolar affective disorders is associated with a variety of renal side effects. The metabolic response of the kidney to chronic Li treatment has rarely been studied. We applied a novel method of (1)H-nuclear magnetic resonance (NMR)-based metabonomics to integrate metabolic profiling and to identify the changes in the levels of metabolites in the kidney and urine from rats with Li-induced NDI. Metabolic profiles of urine and kidney homogenate [3 different zones (cortex, outer medulla, and inner medulla) or whole kidney] were investigated using high-resolution NMR spectroscopy coupled with pattern recognition methods. The accurate concentrations of metabolites in kidney homogenates and urine were rapidly measured using the target-profiling procedure, and the difference in the levels of metabolites was compared using multivariate analysis, such as principal component analysis and orthogonal partial least squares-discriminant analysis. Major endogenous metabolites for kidney homogenates contained products of glycolysis (glucose, lactate) and amino acids, as well as organic osmolytes (e.g., betaine, myo-inositol, taurine, and glycerophosphocholine). Many metabolites revealed changes in their levels, including decreased levels of organic osmolytes and amino acids in the inner medulla. A number of urinary metabolites were changed in Li-induced NDI, and in particular, elevated urinary levels of acetate, lactate, allantoin, trimethylamine, and creatine could suggest Li-induced renal cell stress or injury. Taken together, metabonomics of kidney tissue and urine based on (1)H-NMR spectroscopy could provide insight into the effects of Li-induced renal effects and cell injury.

  5. NMR-based urine analysis in rats: prediction of proximal tubule kidney toxicity and phospholipidosis.

    Science.gov (United States)

    Lienemann, Kai; Plötz, Thomas; Pestel, Sabine

    2008-01-01

    The aim of safety pharmacology is early detection of compound-induced side-effects. NMR-based urine analysis followed by multivariate data analysis (metabonomics) identifies efficiently differences between toxic and non-toxic compounds; but in most cases multiple administrations of the test compound are necessary. We tested the feasibility of detecting proximal tubule kidney toxicity and phospholipidosis with metabonomics techniques after single compound administration as an early safety pharmacology approach. Rats were treated orally, intravenously, inhalatively or intraperitoneally with different test compounds. Urine was collected at 0-8 h and 8-24 h after compound administration, and (1)H NMR-patterns were recorded from the samples. Variation of post-processing and feature extraction methods led to different views on the data. Support Vector Machines were trained on these different data sets and then aggregated as experts in an Ensemble. Finally, validity was monitored with a cross-validation study using a training, validation, and test data set. Proximal tubule kidney toxicity could be predicted with reasonable total classification accuracy (85%), specificity (88%) and sensitivity (78%). In comparison to alternative histological studies, results were obtained quicker, compound need was reduced, and very importantly fewer animals were needed. In contrast, the induction of phospholipidosis by the test compounds could not be predicted using NMR-based urine analysis or the previously published biomarker PAG. NMR-based urine analysis was shown to effectively predict proximal tubule kidney toxicity after single compound administration in rats. Thus, this experimental design allows early detection of toxicity risks with relatively low amounts of compound in a reasonably short period of time.

  6. A Systematic, Integrated Study on the Neuroprotective Effects of Hydroxysafflor Yellow A Revealed by H1 NMR-Based Metabonomics and the NF-κB Pathway

    Directory of Open Access Journals (Sweden)

    Yuanyan Liu

    2013-01-01

    Full Text Available Hydroxysafflor yellow A (HSYA is the main active component of the Chinese herb Carthamus tinctorius L.. Purified HSYA is used as a neuroprotective agent to prevent cerebral ischemia. Injectable safflor yellow (50 mg, containing 35 mg HSYA is widely used to treat patients with ischemic cardiocerebrovascular disease. However, it is unknown how HSYA exerts a protective effect on cerebral ischemia at the molecular level. A systematical integrated study, including histopathological examination, neurological evaluation, blood-brain barrier (BBB, metabonomics, and the nuclear factor-κB (NF-κB pathway, was applied to elucidate the pathophysiological mechanisms of HSYA neuroprotection at the molecular level. HSYA could travel across the BBB, significantly reducing the infarct volume and improving the neurological functions of rats with ischemia. Treatment with HSYA could lead to relative corrections of the impaired metabolic pathways through energy metabolism disruption, excitatory amino acid toxicity, oxidative stress, and membrane disruption revealed by 1H NMR-based metabonomics. Meanwhile, HSYA treatment inhibits the NF-κB pathway via suppressing proinflammatory cytokine expression and p65 translocation and binding activity while upregulating an anti-inflammatory cytokine.

  7. Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

    DEFF Research Database (Denmark)

    Young, Jette Feveile; Larsen, Lotte Bach; Malmendal, Anders

    2010-01-01

    of protein separation was pI 5-8 and second dimension was a 12.5% Criterion gel. Differentially expressed protein spots of significance were excised from the gel, desalted and identified by peptide mass fingerprinting using MALDI-TOF MS. For NMR metabonomic studies, chloroform/methanol extractions....... The identified differentially regulated proteins were related to energy metabolism, glucose regulated stress, cellular structure and the antioxidative defence system. The suggested improvement of the antioxidative defence was confirmed by a reduced intracellular DCFH2 oxidation with increasing concentrations...... of CMH in the 24 h pre-incubation medium. CONCLUSIONS: The explorative approach of this study combined with the determination of a decreased intracellular DCFH2 oxidation revealed an additional stimulation of cellular antioxidative mechanisms when myotubes were exposed to CMH. This may contribute...

  8. Creatine-induced activation of antioxidative defence in myotube cultures revealed by explorative NMR-based metabonomics and proteomics

    Directory of Open Access Journals (Sweden)

    Nielsen Niels

    2010-02-01

    Full Text Available Abstract Background Creatine is a key intermediate in energy metabolism and supplementation of creatine has been used for increasing muscle mass, strength and endurance. Creatine supplementation has also been reported to trigger the skeletal muscle expression of insulin like growth factor I, to increase the fat-free mass and improve cognition in elderly, and more explorative approaches like transcriptomics has revealed additional information. The aim of the present study was to reveal additional insight into the biochemical effects of creatine supplementation at the protein and metabolite level by integrating the explorative techniques, proteomics and NMR metabonomics, in a systems biology approach. Methods Differentiated mouse myotube cultures (C2C12 were exposed to 5 mM creatine monohydrate (CMH for 24 hours. For proteomics studies, lysed myotubes were analyzed in single 2-DGE gels where the first dimension of protein separation was pI 5-8 and second dimension was a 12.5% Criterion gel. Differentially expressed protein spots of significance were excised from the gel, desalted and identified by peptide mass fingerprinting using MALDI-TOF MS. For NMR metabonomic studies, chloroform/methanol extractions of the myotubes were subjected to one-dimensional 1H NMR spectroscopy and the intracellular oxidative status of myotubes was assessed by intracellular DCFH2 oxidation after 24 h pre-incubation with CMH. Results The identified differentially expressed proteins included vimentin, malate dehydrogenase, peroxiredoxin, thioredoxin dependent peroxide reductase, and 75 kDa and 78 kDa glucose regulated protein precursors. After CMH exposure, up-regulated proteomic spots correlated positively with the NMR signals from creatine, while down-regulated proteomic spots were negatively correlated with these NMR signals. The identified differentially regulated proteins were related to energy metabolism, glucose regulated stress, cellular structure and the

  9. Serum metabonomic analysis of protective effects of Curcuma aromatica oil on renal fibrosis rats.

    Science.gov (United States)

    Zhao, Liangcai; Zhang, Haiyan; Yang, Yunjun; Zheng, Yongquan; Dong, Minjian; Wang, Yaqiang; Bai, Guanghui; Ye, Xinjian; Yan, Zhihan; Gao, Hongchang

    2014-01-01

    Curcuma aromatica oil is a traditional herbal medicine demonstrating protective and anti-fibrosis activities in renal fibrosis patients. However, study of its mechanism of action is challenged by its multiple components and multiple targets that its active agent acts on. Nuclear magnetic resonance (NMR)-based metabonomics combined with clinical chemistry and histopathology examination were performed to evaluate intervening effects of Curcuma aromatica oil on renal interstitial fibrosis rats induced by unilateral ureteral obstruction. The metabolite levels were compared based on integral values of serum 1H NMR spectra from rats on 3, 7, 14, and 28 days after the medicine administration. Time trajectory analysis demonstrated that metabolic profiles of the agent-treated rats were restored to control levels after 7 days of dosage. The results confirmed that the agent would be an effective anti-fibrosis medicine in a time-dependent manner, especially in early renal fibrosis stage. Targeted metabolite analysis showed that the medicine could lower levels of lipid, acetoacetate, glucose, phosphorylcholine/choline, trimethylamine oxide and raise levels of pyruvate, glycine in the serum of the rats. Serum clinical chemistry and kidney histopathology examination dovetailed well with the metabonomics data. The results substantiated that Curcuma aromatica oil administration can ameliorate renal fibrosis symptoms by inhibiting some metabolic pathways, including lipids metabolism, glycolysis and methylamine metabolism, which are dominating targets of the agent working in vivo. This study further strengthens the novel analytical approach for evaluating the effect of traditional herbal medicine and elucidating its molecular mechanism.

  10. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    International Nuclear Information System (INIS)

    Feng Jianghua; Liu Huili; Zhang Limin; Bhakoo, Kishore; Lu Lehui

    2010-01-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary α-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary α-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (β-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  11. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids

    Energy Technology Data Exchange (ETDEWEB)

    Feng Jianghua [Department of Physics, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen, 361005 (China); Liu Huili; Zhang Limin [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071 (China); Bhakoo, Kishore [Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A-STAR) 138667 (Singapore); Lu Lehui, E-mail: jianghua.feng@hotmail.com, E-mail: jianghua.feng@wipm.ac.cn [State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022 (China)

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary {alpha}-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary {alpha}-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies ({beta}-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of

  12. An insight into the metabolic responses of ultra-small superparamagnetic particles of iron oxide using metabonomic analysis of biofluids.

    Science.gov (United States)

    Feng, Jianghua; Liu, Huili; Zhang, Limin; Bhakoo, Kishore; Lu, Lehui

    2010-10-01

    Ultra-small superparamagnetic particles of iron oxides (USPIO) have been developed as intravenous organ/tissue-targeted contrast agents to improve magnetic resonance imaging (MRI) in vivo. However, their potential toxicity and effects on metabolism have attracted particular attention. In the present study, uncoated and dextran-coated USPIO were investigated by analyzing both rat urine and plasma metabonomes using high-resolution NMR-based metabonomic analysis in combination with multivariate statistical analysis. The wealth of information gathered on the metabolic profiles from rat urine and plasma has revealed subtle metabolic changes in response to USPIO administration. The metabolic changes include the elevation of urinary alpha-hydroxy-n-valerate, o- and p-HPA, PAG, nicotinate and hippurate accompanied by decreases in the levels of urinary alpha-ketoglutarate, succinate, citrate, N-methylnicotinamide, NAG, DMA, allantoin and acetate following USPIO administration. The changes associated with USPIO administration included a gradual increase in plasma glucose, N-acetyl glycoprotein, saturated fatty acid, citrate, succinate, acetate, GPC, ketone bodies (beta-hydroxybutyrate, acetone and acetoacetate) and individual amino acids, such as phenylalanine, lysine, isoleucine, glycine, glutamine and glutamate and a gradual decrease of myo-inositol, unsaturated fatty acid and triacylglycerol. Hence USPIO administration effects are reflected in changes in a number of metabolic pathways including energy, lipid, glucose and amino acid metabolism. The size- and surface chemistry-dependent metabolic responses and possible toxicity were observed using NMR analysis of biofluids. These changes may be attributed to the disturbances of hepatic, renal and cardiac functions following USPIO administrations. The potential biotoxicity can be derived from metabonomic analysis and serum biochemistry analysis. Metabonomic strategy offers a promising approach for the detection of subtle

  13. Two-dimensional liquid chromatography and its application in traditional Chinese medicine analysis and metabonomic investigation.

    Science.gov (United States)

    Li, Zheng; Chen, Kai; Guo, Meng-zhe; Tang, Dao-quan

    2016-01-01

    Two-dimensional liquid chromatography has become an attractive analytical tool for the separation of complex samples due to its enhanced selectivity, peak capacity, and resolution compared with one-dimensional liquid chromatography. Recently, more attention has been drawn on the application of this separation technique in studies concerning traditional Chinese medicines, metabonomes, proteomes, and other complex mixtures. In this review, we aim to examine the application of two-dimensional liquid chromatography in traditional Chinese medicine analysis and metabonomic investigation. The classification and evaluation indexes were first introduced. Then, various switching methods were summarized when used in an on-line two-dimensional liquid chromatography system. Finally, the applications of this separation technique in traditional Chinese medicine analysis and metabonomic investigation were discussed on the basis of specific studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Metabonomic analysis of rats with acute heart rejection.

    Science.gov (United States)

    Tao, M; Xiu, D R

    2013-03-01

    Organs transplantation is an effective treatment for end-stage organ failure. Despite the use of modern immunosuppressants to decrease its incidence, acute rejection episodes (ARE), still present a problem for diagnosis, resolution, and prediction of long-term outcomes due to the absence of sufficiently robust biomarkers. Using an heterotopic heart transplantation model using Dark Agouti to Lewis rats, and sirolimus (rapamycin, Rapa) treatment by gavage, we divided recipients into four groups: controls, ARE, Rapa-14, and Rapa-7. We evaluated recipients by hematoxylin and eosin staining of grafts and reverse transcription polymerase chain reactions. Levels of plasma metabolites were quantified using gas chromatography/time-of-flight mass spectrometry. Data were evaluated employing partial least-squares discriminant analysis (PLS-DA), the area under the receiver operating characteristic curves with negative predictive values (NPV) and positive predictive values (PPV). The graft survival was prolonged by Rapa. Plasma levels of 10 metabolites differed significantly between the ARE and the Rapa-14 groups as illustrated by the total ion current. According to PLS-DA, proline, glycine, serine, phenylalanine, and isocitrate showed the greatest effects with areas under the curve of 0.944, 0.917, 1.0, 0.861, and 0.944 respectively. The NPV values were 85.7%, 85.7%, 100%, 83.3%, and 85.7% and PPV values, 100%, 100%, 100%, 83.3%, and 100% respectively. Therefore, these metabolites may be used to predict the occurrence and progression of ARE. The trend of changes suggested that plasma metabolites correlated with the immune state of recipients. Therefore, metabonomics may provide new biomarkers for graft injury in the early phases of ARE. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

  15. Integrated GC-MS and LC-MS plasma metabonomics analysis of ankylosing spondylitis.

    Science.gov (United States)

    Gao, Peng; Lu, Chen; Zhang, Fengxia; Sang, Ping; Yang, Dawei; Li, Xiang; Kong, Hongwei; Yin, Peiyuan; Tian, Jing; Lu, Xin; Lu, Aiping; Xu, Guowang

    2008-09-01

    Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that predominantly affects the axial skeleton in adolescent patients. The natural history of the disease remains poorly characterized. In this study, we combined GC-MS and LC-MS techniques to evaluate the major metabolic changes in the plasma of AS patients in view of metabonomics. Univariate and multivariate analysis were employed for altered metabolite comparison and pattern recognition. Application of supervised partial least-squares discrminant analysis to either GC-MS or LC-MS data allowed accurate discrimination of AS patients from normal controls, demonstrating its potential diagnostic utilization. In addition, AS patients presented elevated plasma concentrations of proline, glucose, phosphate, urea, glycerol, phenylalanine and homocysteine but reduced levels of phosphocholines, tryptophan and a bipeptide - phenylalanyl-phenylalanine. In the context of their involved metabolic pathways, the identified metabolites were discussed accordingly. This investigation primarily proved that integrated chromatography-mass spectrometry and integrated uni- and multi-variate statistical analysis facilitated metabonomics to be a more promising tool in disease research.

  16. NMR-based screening method for transglutaminases: rapid analysis of their substrate specificities and reaction rates.

    Science.gov (United States)

    Shimba, Nobuhisa; Yokoyama, Kei-ichi; Suzuki, Ei-ichiro

    2002-03-13

    Incorporation of inter- or intramolecular covalent cross-links into food proteins with microbial transglutaminase (MTG) improves the physical and textural properties of many food proteins such as tofu, boiled fish paste, and sausage. Other transglutaminases (TGases) are expected to be used in the same way, and also to extend the scope of industrial applications to materials, drugs, and so on. The TGases have great diversity, not only in amino acid sequence and size, but also in their substrate specificities and catalytic activities, and therefore, it is quite difficult to estimate their reactivity. We have developed an NMR-based method using the enzymatic labeling technique (ELT) for simultaneous analysis of the substrate specificities and reaction rates of TGases. It is quite useful for comparing the existing TGases and for screening new TGases or TGases variants. This method has shown that MTG is superior for industrial use because of its lower substrate specificity compared with those of guinea pig liver transglutaminase (GTG) and red sea bream liver transglutaminase (FTG). We have also found that an MTG variant lacking an N-terminal aspartic acid residue has higher activity than that of the native enzyme.

  17. Urine metabolite analysis as a function of deoxynivalenol exposure: an NMR-based metabolomics investigation.

    Science.gov (United States)

    Hopton, R P; Turner, E; Burley, V J; Turner, P C; Fisher, J

    2010-02-01

    Deoxynivalenol (DON) is a toxic fungal metabolite that frequently contaminates cereal crops including wheat, maize and barley. Despite knowledge of frequent exposure through diet, our understanding of the potential consequences of human exposure remains limited, in part due to the lack of validated exposure biomarkers. In this study, we interrogated the urinary metabolome using nuclear magnetic resonance (NMR) spectroscopy to compare individuals with known low and high DON exposure through consumption of their normal diet. Urine samples from 22 adults from the UK (seven males, 15 females; age range = 21-59 years) had previously determined urinary DON levels using an established liquid chromatography-mass spectrometry (LC-MS) assay. Urine samples were subsequently analysed using an NMR-based metabolomics approach coupled with multivariate statistical analysis. Metabolic profiling suggested that hippurate levels could be used to distinguish between groups with low (3.6 ng DON mg(-1) creatinine: 95% CI = 2.6, 5.0 ng mg(-1)) and high (11.1 ng mg(-1): 95% CI = 8.1, 15.5 ng mg(-1)) DON exposure, with the concentration of hippurate being significantly (1.5 times) higher for people with high DON exposure than for those with low DON exposure (p = 0.047). This, to our knowledge, is the first report of a metabolomics-derived biomarker of DON exposure in humans.

  18. Metabonomic analysis of Bombyx mori (Heterocera: Bombysidae) treated with acetaminophen.

    Science.gov (United States)

    Yin, W M; Xu, X; He, Y; Wei, G B; Sima, Y H; Shi-Qing, Xu

    2014-01-01

    The feasibility of using Bombyx mori as model animal is attracting more attention. Whether the effect of drugs on the metabolite profiling was consistent with those in mammals was an aspect to evaluate the feasibility of B. mori as model animal. In this study, we used acetaminophen to treat Dazao fifth-instar B. mori, and its metabolites in hemolymph were detected by gas chromatography-mass spectrometry. The corresponding data were processed and analyzed by total model analysis, principal component analysis, partial least squares-discriminant analysis, orthogonal partial least squares-discriminant analysis, and finally, the difference metabolites between acetaminophen group and control group were selected and identified by our reference material database and the National Institute of Standard and Technology database. The results showed that acetaminophen administration induced elevation of metabolites related to energy source, the intermediate of cholesterol synthesis, and the metabolites related to melanization and also induced the decrease of metabolites in pathway of Krebs cycle, the cholesterol, and sitosterol, which suggested that acetaminophen administration inhibited energy metabolism and promoted the expenditure and imbalance of hormone and melanization. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

  19. The application of NMR-based milk metabolite analysis in milk authenticity identification.

    Science.gov (United States)

    Li, Qiangqiang; Yu, Zunbo; Zhu, Dan; Meng, Xianghe; Pang, Xiumei; Liu, Yue; Frew, Russell; Chen, He; Chen, Gang

    2017-07-01

    Milk is an important food component in the human diet and is a target for fraud, including many unsafe practices. For example, the unscrupulous adulteration of soymilk into bovine and goat milk or of bovine milk into goat milk in order to gain profit without declaration is a health risk, as the adulterant source and sanitary history are unknown. A robust and fit-for-purpose technique is required to enforce market surveillance and hence protect consumer health. Nuclear magnetic resonance (NMR) is a powerful technique for characterization of food products based on measuring the profile of metabolites. In this study, 1D NMR in conjunction with multivariate chemometrics as well as 2D NMR was applied to differentiate milk types and to identify milk adulteration. Ten metabolites were found which differed among milk types, hence providing characteristic markers for identifying the milk. These metabolites were used to establish mathematical models for milk type differentiation. The limit of quantification (LOQ) of adulteration was 2% (v/v) for soymilk in bovine milk, 2% (v/v) for soymilk in goat milk and 5% (v/v) for bovine milk in goat milk, with relative standard deviation (RSD) less than 10%, which can meet the needs of daily inspection. The NMR method described here is effective for milk authenticity identification, and the study demonstrates that the NMR-based milk metabolite analysis approach provides a means of detecting adulteration at expected levels and can be used for dairy quality monitoring. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  20. Serum metabonomics coupled with Ingenuity Pathway Analysis characterizes metabolic perturbations in response to hypothyroidism induced by propylthiouracil in rats.

    Science.gov (United States)

    Wu, Si; Gao, Yue; Dong, Xin; Tan, Guangguo; Li, Wuhong; Lou, Ziyang; Chai, Yifeng

    2013-01-01

    A serum metabonomic profiling method based on ultra-performance liquid chromatography/time-of-flight mass spectrometry (UHPLC/TOF-MS) was applied to investigate the metabolic changes in hypothyroid rats induced by propylthiouracil (PTU). With Significance Analysis of Microarray (SAM) for classification and selection of biomarkers, 13 potential biomarkers in rat serum were screened out. Furthermore, Ingenuity Pathway Analysis (IPA) was introduced to deeply analyze unique pathways of hypothyroidism that were primarily involved in sphingolipid metabolism, fatty acid transportation, phospholipid metabolism and phenylalanine metabolism. Our results demonstrated that the metabonomic approach integrating with IPA was a promising tool for providing a novel methodological clue to systemically dissect the underlying molecular mechanism of hypothyroidism. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Metabonomics profiling of marinated meat in soy sauce during processing.

    Science.gov (United States)

    Yang, Yang; Ye, Yangfang; Pan, Daodong; Sun, Yangying; Wang, Ying; Cao, Jinxuan

    2018-03-01

    Marinated meat in soy sauce is one of the most popular traditional cured meat products in China. Its taste quality is directly related to primary and secondary metabolites. Herein, the change of metabolite composition of marinated meat in soy sauce during processing was systematically characterised using 1 H NMR and multivariate data analysis. The marinated meat in soy sauce metabonome was dominated by 26 metabolites, including amino acids, sugars, organic acids, nucleic aides and their derivatives. PC1 and PC2 explained a total of 78.6% and 16.6% of variables, respectively. Amino acids, sugars, acetate, succinate, uracil and inosine increased during marinating, while lactate, creatine, inosine-5'-monophosphate (5'-IMP) and anserine decreased (P soy sauce during the late stage of dry-ripening. These findings indicated that the potential of NMR-based metabonomics is of importance for taste quality of marinated meat in soy sauce, which could contribute to a better understanding of the changes of taste compounds in meat products during processing. Shortening the dry-ripening period could be considered to improve the taste quality. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

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

    Science.gov (United States)

    Emwas, Abdul-Hamid; Roy, Raja; McKay, Ryan T; Ryan, Danielle; Brennan, Lorraine; Tenori, Leonardo; Luchinat, Claudio; Gao, Xin; Zeri, Ana Carolina; Gowda, G A Nagana; Raftery, Daniel; Steinbeck, Christoph; Salek, Reza M; Wishart, David S

    2016-02-05

    NMR-based metabolomics has shown considerable promise in disease diagnosis and biomarker discovery because it allows one to nondestructively identify and quantify large numbers of novel metabolite biomarkers in both biofluids and tissues. Precise metabolite quantification is a prerequisite to move any chemical biomarker or biomarker panel from the lab to the clinic. Among the biofluids commonly used for disease diagnosis and prognosis, urine has several advantages. It is abundant, sterile, and easily obtained, needs little sample preparation, and does not require invasive medical procedures for collection. Furthermore, urine captures and concentrates many "unwanted" or "undesirable" compounds throughout the body, providing a rich source of potentially useful disease biomarkers; however, incredible variation in urine chemical concentrations makes analysis of urine and identification of useful urinary biomarkers by NMR challenging. We discuss a number of the most significant issues regarding NMR-based urinary metabolomics with specific emphasis on metabolite quantification for disease biomarker applications and propose data collection and instrumental recommendations regarding NMR pulse sequences, acceptable acquisition parameter ranges, relaxation effects on quantitation, proper handling of instrumental differences, sample preparation, and biomarker assessment.

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

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2016-01-08

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

  4. Introducing Undergraduate Students to Metabolomics Using a NMR-Based Analysis of Coffee Beans

    Science.gov (United States)

    Sandusky, Peter Olaf

    2017-01-01

    Metabolomics applies multivariate statistical analysis to sets of high-resolution spectra taken over a population of biologically derived samples. The objective is to distinguish subpopulations within the overall sample population, and possibly also to identify biomarkers. While metabolomics has become part of the standard analytical toolbox in…

  5. NMR-Based Metabolomic Analysis of Spatial Variation in Soft Corals

    Directory of Open Access Journals (Sweden)

    Qing He

    2014-03-01

    Full Text Available Soft corals are common marine organisms that inhabit tropical and subtropical oceans. They are shown to be rich source of secondary metabolites with biological activities. In this work, soft corals from two geographical locations were investigated using 1H-NMR spectroscopy coupled with multivariate statistical analysis at the metabolic level. A partial least-squares discriminant analysis showed clear separation among extracts of soft corals grown in Sanya Bay and Weizhou Island. The specific markers that contributed to discrimination between soft corals in two origins belonged to terpenes, sterols and N-containing compounds. The satisfied precision of classification obtained indicates this approach using combined 1H-NMR and chemometrics is effective to discriminate soft corals collected in different geographical locations. The results revealed that metabolites of soft corals evidently depended on living environmental condition, which would provide valuable information for further relevant coastal marine environment evaluation.

  6. NMR-based Metabolomics Analysis of Liver from C57BL/6 Mouse Exposed to Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Xiao, Xiongjie [Pacific Northwest National Laboratory, Richland, Washington 99352; State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, the Chinese Academy of Sciences, Wuhan, 430071, PR China; University of Chinese Academy of Sciences, Beijing 100049, China; Hu, Mary [Pacific Northwest National Laboratory, Richland, Washington 99352; Zhang, Xu [State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, the Chinese Academy of Sciences, Wuhan, 430071, PR China; Hu, Jian Zhi [Pacific Northwest National Laboratory, Richland, Washington 99352

    2017-07-01

    The health effects of exposing to ionizing radiation are attracting great interest in the space exploration community and patients considering radiotherapy. However, the impact to metabolism after exposure to high dose radiation has not yet been clearly defined in livers. In the present study, 1H nuclear magnetic resonance (NMR) based metabolomics combined with multivariate data analysis are applied to study the changes of metabolism in the liver of C57BL/6 mouse after whole body exposure to either gamma (3.0 and 7.8 Gy) or proton (3.0 Gy) radiation. Principal component analysis (PCA) and orthogonal projection to latent structures analysis (OPLS) are employed for classification and identification of potential biomarkers associated with gamma and proton irradiation. The results show that the radiation exposed groups can be well separated from the control group. At the same radiation dosage, the group exposed to proton radiation is well separated from the group exposed to gamma radiation, indicating different radiation sources induce different alterations based on metabolic profiling. Common to both gamma and proton radiation at the high radiation doses studied in this work, compared with the control groups the concentrations of choline, O-phosphocholine and trimethylamine N-oxide are decreased statistically, while those of glutamine, glutathione, malate, creatinine, phosphate, betaine and 4-hydroxyphenylacetate are statistically and significantly elevated after exposure to radiation. Since these altered metabolites are associated with multiple biological pathways, the changes suggest that the exposure to radiation induce abnormality in multiple biological pathways. In particular, metabolites such as 4-hydroxyphenylacetate, betaine, glutamine, choline and trimethylamine N-oxide may be good candidates of pre-diagnose biomarkers for ionizing radiation in liver.

  7. Discriminating poststroke depression from stroke by nuclear magnetic resonance spectroscopy-based metabonomic analysis

    Directory of Open Access Journals (Sweden)

    Xiao J

    2016-08-01

    Full Text Available Jianqi Xiao,1,* Jie Zhang,2,* Dan Sun,3,* Lin Wang,4,* Lijun Yu,5 Hongjing Wu,5 Dan Wang,5 Xuerong Qiu5 1Department of Neurosurgery, The First Hospital of Qiqihar City, Qiqihar, 2Department of Internal Medicine, Central Hospital of Jiamusi City, Jiamusi, 3Department of Geriatrics, General Hospital of Daqing Oil Field, Daqing, 4Department of Nursing, 5Department of Neurology, The First Hospital of Qiqihar City, Qiqihar, Heilongjiang, People’s Republic of China *These authors contributed equally to this work Abstract: Poststroke depression (PSD, the most common psychiatric disease that stroke survivors face, is estimated to affect ~30% of poststroke patients. However, there are still no objective methods to diagnose PSD. In this study, to explore the differential metabolites in the urine of PSD subjects and to identify a potential biomarker panel for PSD diagnosis, the nuclear magnetic resonance-based metabonomic method was applied. Ten differential metabolites responsible for discriminating PSD subjects from healthy control (HC and stroke subjects were found, and five of these metabolites were identified as potential biomarkers (lactate, α-hydroxybutyrate, phenylalanine, formate, and arabinitol. The panel consisting of these five metabolites provided excellent performance in discriminating PSD subjects from HC and stroke subjects, achieving an area under the receiver operating characteristic curve of 0.946 in the training set (43 HC, 45 stroke, and 62 PSD subjects. Moreover, this panel could classify the blinded samples from the test set (31 HC, 33 stroke, and 32 PSD subjects with an area under the curve of 0.946. These results laid a foundation for the future development of urine-based objective methods for PSD diagnosis and investigation of PSD pathogenesis. Keywords: poststroke depression, PSD, stroke, nuclear magnetic resonance, NMR, metabonomic

  8. 1H NMR-Based Metabolomic Analysis of Sub-Lethal Perfluorooctane Sulfonate Exposure to the Earthworm, Eisenia fetida, in Soil

    Directory of Open Access Journals (Sweden)

    Myrna J. Simpson

    2013-08-01

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

  9. (1)H-NMR-based metabolomic analysis of the effect of moderate wine consumption on subjects with cardiovascular risk factors

    OpenAIRE

    Vázquez Fresno, Rosa; Llorach, Rafael; Alcaro, Francesca; Rodríguez Martínez, Miguel Ángel; Vinaixa Crevillent, Maria; Chiva Blanch, Gemma; Estruch Riba, Ramon; Correig Blanchar, Xavier; Andrés Lacueva, Ma. Cristina

    2012-01-01

    Moderate wine consumption is associated with health-promoting activities. An H-NMR-based metabolomic approach was used to identify urinary metabolomic differences of moderate wine intake in the setting of a prospective, randomized, crossover, and controlled trial. Sixty-one male volunteers with high cardiovascular risk factors followed three dietary interventions (28 days): dealcoholized red wine (RWD) (272mL/day, polyphenol control), alcoholized red wine (RWA) (272mL/day) and gin (GIN) (100m...

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

    Science.gov (United States)

    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

  11. Application of Metabonomics in Early Diagnosis of Diseases

    OpenAIRE

    Qiao LIU

    2015-01-01

    With the development of life sciences, people have changed their focus from local research to systematic biology, thus contributing to the development of a series of “omics”, including genomics, transcriptomics, proteomics and metabonomics, etc. Metabonomics is a presently developed new branch of science that can provide qualitative and quantitative analysis on all metabolites with low-molecular quality in the body, tissues or cells of an organism. It recognizes the changes and rules of the b...

  12. Integrated metabonomics analysis of the size-response relationship of silica nanoparticles-induced toxicity in mice

    Energy Technology Data Exchange (ETDEWEB)

    Lu Xiaoyan; Tian Yu; Zhao Qinqin; Jin Tingting; Xiao Shun; Fan Xiaohui, E-mail: fanxh@zju.edu.cn [Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058 (China)

    2011-02-04

    Understanding the underlying properties-dependent interactions of nanostructures with biological systems is essential to nanotoxicological research. This study investigates the relationship between particle size and toxicity, and further reveals the mechanism of injury, using silica particles (SP) with diameters of 30, 70, and 300 nm (SP30, SP70, and SP300) as model materials. The biochemical compositions of liver tissues and serum of mice treated with SP30, SP70, and SP300 were analyzed by integrated metabonomics analysis based on gas chromatography-mass spectrometry (GC-MS) and in combination with pattern recognition approaches. Histopathological examinations and serum biochemical analysis were simultaneously performed. The toxicity induced by three different sizes of SP mainly involved hepatocytic necrosis, increased serum aminotransferase, and inflammatory cytokines. Moreover, the toxic effects of SP were dose-dependent for each particle size. The doses of SP30, SP70, and SP300 that were toxic to the liver were 10, 40, and 200 mg kg{sup -1}, respectively. In this study, surface area has a greater effect than particle number on the toxicity of SP30, SP70, and SP300 in the liver. The disturbances in energy metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism may be attributable to the hepatotoxicity induced by SP. In addition, no major differences were found in the response of biological systems caused by the different SP sizes among the metabolite profiles. The results suggest that not only nano-sized but also submicro-sized SP can cause similar extents of liver injury, which is dependent on the exposure dose, and the mechanism of toxicity may be almost the same.

  13. Discriminative Analysis of Different Grades of Gaharu (Aquilaria malaccensis Lamk. via 1H-NMR-Based Metabolomics Using PLS-DA and Random Forests Classification Models

    Directory of Open Access Journals (Sweden)

    Siti Nazirah Ismail

    2017-09-01

    Full Text Available Gaharu (agarwood, Aquilaria malaccensis Lamk. is a valuable tropical rainforest product traded internationally for its distinctive fragrance. It is not only popular as incense and in perfumery, but also favored in traditional medicine due to its sedative, carminative, cardioprotective and analgesic effects. The current study addresses the chemical differences and similarities between gaharu samples of different grades, obtained commercially, using 1H-NMR-based metabolomics. Two classification models: partial least squares-discriminant analysis (PLS-DA and Random Forests were developed to classify the gaharu samples on the basis of their chemical constituents. The gaharu samples could be reclassified into a ‘high grade’ group (samples A, B and D, characterized by high contents of kusunol, jinkohol, and 10-epi-γ-eudesmol; an ‘intermediate grade’ group (samples C, F and G, dominated by fatty acid and vanillic acid; and a ‘low grade’ group (sample E and H, which had higher contents of aquilarone derivatives and phenylethyl chromones. The results showed that 1H- NMR-based metabolomics can be a potential method to grade the quality of gaharu samples on the basis of their chemical constituents.

  14. Integration of transcriptomics and metabonomics

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Rantalainen, Mattias; Wang, Yulan

    2014-01-01

    the possibilities of a molecular phenotyping of ulcerative colitis (UC) patients. Biopsies were obtained from the descending colon of 43 UC patients (22 active UC and 21 quiescent UC) and 15 controls. Genome-wide gene expression analyses were performed using Affymetrix GeneChip Human Genome U133 Plus 2.0. Metabolic...... profiles were generated using (1)H Nuclear magnetic resonance spectroscopy (Bruker 600 MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with the use of orthogonal-projection to latent structure-discriminant analysis and a multivariate logistic regression model fitted by lasso. Prediction...... with or without steroid dependency, as well as between early or late disease onset. Consequently, this study demonstrates that the novel approach of integrating metabonomics and transcriptomics combines the better of the two worlds, and provides us with clinical applicable candidate biomarker panels...

  15. Metabonomic Analysis Reveals Efficient Ameliorating Effects of Acupoint Stimulations on the Menopause-caused Alterations in Mammalian Metabolism

    Science.gov (United States)

    Zhang, Limin; Wang, Yulan; Xu, Yunxiang; Lei, Hehua; Zhao, Ying; Li, Huihui; Lin, Xiaosheng; Chen, Guizhen; Tang, Huiru

    2014-01-01

    Acupoint stimulations are effective in ameliorating symptoms of menopause which is an unavoidable ageing consequence for women. To understand the mechanistic aspects of such treatments, we systematically analyzed the effects of acupoint laser-irradiation and catgut-embedding on the ovariectomy-induced rat metabolic changes using NMR and GC-FID/MS methods. Results showed that ovariectomization (OVX) caused comprehensive metabolic changes in lipid peroxidation, glycolysis, TCA cycle, choline and amino acid metabolisms. Both acupoint laser-irradiation and catgut-embedding ameliorated the OVX-caused metabonomic changes more effectively than hormone replacement therapy (HRT) with nilestriol. Such effects of acupoint stimulations were highlighted in alleviating lipid peroxidation, restoring glucose homeostasis and partial reversion of the OVX-altered amino acid metabolism. These findings provided new insights into the menopause effects on mammalian biochemistry and beneficial effects of acupoint stimulations in comparison with HRT, demonstrating metabonomics as a powerful approach for potential applications in disease prognosis and developments of effective therapies.

  16. A plasma metabonomic analysis on potential biomarker in pyrexia induced by three methods using ultra high performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry.

    Science.gov (United States)

    Liu, Ting; Li, Songhe; Tian, Xiumin; Li, Zhaoqin; Cui, Yue; Han, Fei; Zhao, Yunli; Yu, Zhiguo

    2017-09-15

    Pyrexia usually is a systemic pathological process that can lead to metabolic disorders. Metabonomics as a powerful tool not only can reveal the pathological mechanisms, but also can give insight into the progression of pyrexia from another angle. Thus, an ultra high performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) metabonomic approach was employed for the first time to investigate the plasma biochemical characteristics of pyrexia induced by three methods and to reveal subtle metabolic changes under the condition of pyrexia so as to explore its mechanism. The acquired metabolic data of the models were subjected to principal component analysis (PCA) for allowing the clear separation of the pyrexia rats from the control rats. Variable importance for project values (VIP) and Student's t-test were used to screen the significant metabolic changes caused by pyrexia. Fifty-two endogenous metabolites were identified and putatively identified as potential biomarkers primarily associated with phospholipid metabolism, sphingolipid metabolism, fatty acid oxidation metabolism, fatty acid amides metabolism and amino acid metabolism, and related to bile acid biosynthesis and glycerolipid catabolism. LysoPC (14:0), LysoPC (18:3), LysoPC (20:4), LysoPC (16:0), phytosphingosine, Cer (d18:0/12:0), N-[(4E,8E)-1,3-dihydroxyoctadeca-4,8-dien-2-yl]hexadecanamide, oleamide, fatty acid amide C22:1, tryptophan, acetylcarnitine, palmitoylcarnitine and stearoylcarnitine were considered as common potential biomarkers of pyrexia rats induced by three methods: Our results revealed that the UHPLC-FT-ICR-MS-based metabolomic method is helpful for finding new potential metabolic markers for pyrexia detection and offers a good perspective in pyrexia research. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Application of Metabonomics in Early Diagnosis of Diseases

    Directory of Open Access Journals (Sweden)

    Qiao LIU

    2015-06-01

    Full Text Available With the development of life sciences, people have changed their focus from local research to systematic biology, thus contributing to the development of a series of “omics”, including genomics, transcriptomics, proteomics and metabonomics, etc. Metabonomics is a presently developed new branch of science that can provide qualitative and quantitative analysis on all metabolites with low-molecular quality in the body, tissues or cells of an organism. It recognizes the changes and rules of the biological endogenous substance under the impact of internal and external factors by generally and quantitatively detecting multiple small molecular compounds in biological samples, in hope of finding out the metabolic marker clusters in the early stage of diseases so as to provide new pathways for the early diagnosis of the diseases and the realization of individualized drug administration. Additionally, metabonomics research on clinical diseases has become a hot topic and made great achievement in the developmental condition, diagnostic methods, pathogenic mechanism and pharmaceutical efficacy evaluation of diseases. This study mainly reviewed the application and advances of metabonomics in the early diagnosis of malignant tumors, cardiovascular and respiratory diseases, hoping to provide references and prompts for metabonomics-associated researches.

  18. The variation of root exudates from the hyperaccumulator Sedum alfredii under cadmium stress: metabonomics analysis.

    Directory of Open Access Journals (Sweden)

    Qing Luo

    Full Text Available Hydroponic experiments were conducted to investigate the variation of root exudates from the hyperaccumulator Sedum alfredii under the stress of cadmium (Cd. S. alfredii was cultured for 4 days in the nutrient solution spiked with CdCl2 at concentrations of 0, 5, 10, 40, and 400 µM Cd after the pre-culture. The root exudates were collected and analyzed by GC-MS, and 62 compounds were identified. Of these compounds, the orthogonal partial least-squares discrimination analysis (OPLS-DA showed that there were a distinct difference among the root exudates with different Cd treatments and 20 compounds resulting in this difference were found out. Changing tendencies in the relative content of these 20 compounds under the different Cd treatments were analyzed. These results indicated that trehalose, erythritol, naphthalene, d-pinitol and n-octacosane might be closely related to the Cd stabilization, phosphoric acid, tetradecanoic acid, oxalic acid, threonic acid and glycine could be attributed to the Cd mobilization, and mannitol, oleic acid, 3-hydroxybutanoic acid, fructose, octacosanol and ribitol could copy well with the Cd stress.

  19. NMR-based milk metabolomics

    DEFF Research Database (Denmark)

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

    2013-01-01

    and processing capabilities of bovine milk is closely associated to milk composition. Metabolomics is ideal in the study of the low-molecular-weight compounds in milk, and this review focuses on the recent nuclear magnetic resonance (NMR)-based metabolomics trends in milk research, including applications linking...... the milk metabolite profiling with nutritional aspects, and applications which aim to link the milk metabolite profile to various technological qualities of milk. The metabolite profiling studies encompass the identification of novel metabolites, which potentially can be used as biomarkers or as bioactive...... compounds. Furthermore, metabolomics applications elucidating how the differential regulated genes affects milk composition are also reported. This review will highlight the recent advances in NMR-based metabolomics on milk, as well as give a brief summary of when NMR spectroscopy can be useful for gaining...

  20. 1H NMR-Based Analysis of Serum Metabolites in Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats

    Directory of Open Access Journals (Sweden)

    Taijie Lin

    2016-01-01

    Full Text Available Aims. To study the changes of the metabolic profile during the pathogenesis in monocrotaline (MCT induced pulmonary arterial hypertension (PAH. Methods. Forty male Sprague-Dawley (SD rats were randomly divided into 5 groups (n=8, each. PAH rats were induced by a single dose intraperitoneal injection of 60 mg/kg MCT, while 8 rats given intraperitoneal injection of 1 ml normal saline and scarified in the same day (W0 served as control. Mean pulmonary arterial pressure (mPAP was measured through catherization. The degree of right ventricular hypertrophy and pulmonary hyperplasia were determined at the end of first to fourth weeks; nuclear magnetic resonance (NMR spectra of sera were then acquired for the analysis of metabolites. Principal component analysis (PCA and orthogonal partial least-squares discriminant analysis (OPLS-DA were used to discriminate different metabolic profiles. Results. The prominent changes of metabolic profiles were seen during these four weeks. Twenty specific metabolites were identified, which were mainly involved in lipid metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism. Profiles of correlation between these metabolites in each stage changed markedly, especially in the fourth week. Highly activated methionine and betaine metabolism pathways were selected by the pathway enrichment analysis. Conclusions. Metabolic dysfunction is involved in the development and progression of PAH.

  1. Metabonomic analysis of the protective effect of quercetin on the toxicity induced by mixture of organophosphate pesticides in rat urine.

    Science.gov (United States)

    Qi, L; Cao, C; Hu, L; Chen, S; Zhao, X; Sun, C

    2017-05-01

    The present study aims to investigate the protective effect of quercetin against the joint toxic action induced by the mixture of four organophosphate pesticides (mixture-OPs) (dimethoate, acephate, dichlorvos, and phorate) at their corresponding no observed adverse effect level (NOAEL) using metabonomics. Rats were randomly divided into control, quercetin-treated, mixture-OPs-treated, and quercetin plus mixture-OPs-treated groups. Mixture-OPs and quercetin were given to the rats daily through drinking water and intragastric administration, respectively, for 90 days. The metabonomic profiles of rat urine were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC/MS). The 14 metabolites significantly changed in the treatment groups compared with the control group, including the biomarkers of OPs exposure (dimethylphosphate, dimethyldithiophosphate, diethylphosphate) and the metabolites of quercetin (quercetin and isorhamnetina). The intensities of gentisic acid, creatinine, suberic acid, hippuric acid, uric acid, and citric acid significantly decreased, whereas the intensities of 7-methylguanine, estrone sulfate, and cholic acid significantly increased, in the mixture-OPs-treated group compared with the control group ( p < 0.01). The variation tendency of the aforementioned metabolites was significantly ameliorated in the high-dose quercetin (50 mg/(kg bw day)) plus mixture-OPs-treated group compared with the mixture-OPs-treated group ( p < 0.05). However, the intensities of these metabolites in the high-dose quercetin plus mixture-OPs-treated group were still significantly different from those of the control group ( p < 0.05). Results indicated that high dose of quercetin elicits a partial protective effect on the toxicity induced by mixture-OPs, including fatty acid and energy metabolism, antioxidant defense system, DNA damage, and liver and kidney function.

  2. NMR-based phytochemical analysis of Vitis vinifera cv Falanghina leaves. Characterization of a previously undescribed biflavonoid with antiproliferative activity.

    Science.gov (United States)

    Tartaglione, Luciana; Gambuti, Angelita; De Cicco, Paola; Ercolano, Giuseppe; Ianaro, Angela; Taglialatela-Scafati, Orazio; Moio, Luigi; Forino, Martino

    2018-03-01

    Vitis vinifera cv Falanghina is an ancient grape variety of Southern Italy. A thorough phytochemical analysis of the Falanghina leaves was conducted to investigate its specialised metabolite content. Along with already known molecules, such as caftaric acid, quercetin-3-O-β-d-glucopyranoside, quercetin-3-O-β-d-glucuronide, kaempferol-3-O-β-d-glucopyranoside and kaempferol-3-O-β-d-glucuronide, a previously undescribed biflavonoid was identified. For this last compound, a moderate bioactivity against metastatic melanoma cells proliferation was discovered. This datum can be of some interest to researchers studying human melanoma. The high content in antioxidant glycosylated flavonoids supports the exploitation of grape vine leaves as an inexpensive source of natural products for the food industry and for both pharmaceutical and nutraceutical companies. Additionally, this study offers important insights into the plant physiology, thus prompting possible technological researches of genetic selection based on the vine adaptation to specific pedo-climatic environments. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. 1H-NMR-based metabolic analysis of human serum reveals novel markers of myocardial energy expenditure in heart failure patients.

    Science.gov (United States)

    Du, Zhiyong; Shen, Anna; Huang, Yuli; Su, Liang; Lai, Wenyan; Wang, Peng; Xie, Zhibing; Xie, Zhiquan; Zeng, Qingchun; Ren, Hao; Xu, Dingli

    2014-01-01

    Elevated myocardial energy expenditure (MEE) is related with reduced left ventricular ejection fraction, and has also been documented as an independent predictor of cardiovascular mortality. However, the serum small-molecule metabolite profiles and pathophysiological mechanisms of elevated MEE in heart failure (HF) are still lacking. Herein, we used 1H-NMR-based metabolomics analysis to screen for potential biomarkers of MEE in HF. A total of 61 subjects were enrolled, including 46 patients with heart failure and 15 age-matched controls. Venous serum samples were collected from subjects after an 8-hour fast. An INOVA 600 MHz nuclear magnetic resonance spectrometer with Carr-Purcell-Melboom-Gill (CPMG) pulse sequence was employed for the metabolomics analysis and MEE was calculated using colored Doppler echocardiography. Metabolomics data were processed using orthogonal signal correction and regression analysis was performed using the partial least squares method. The mean MEE levels of HF patients and controls were 139.61±58.18 cal/min and 61.09±23.54 cal/min, respectively. Serum metabolomics varied with MEE changed, and 3-hydroxybutyrate, acetone and succinate were significantly elevated with the increasing MEE. Importantly, these three metabolites were independent of administration of angiotensin converting enzyme inhibitor, β-receptor blockers, diuretics and statins (P>0.05). These results suggested that in patients with heart failure, MEE elevation was associated with significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate. These compounds could be used as potential serum biomarkers to study myocardial energy mechanism in HF patients.

  4. 1H-NMR-based metabolic analysis of human serum reveals novel markers of myocardial energy expenditure in heart failure patients.

    Directory of Open Access Journals (Sweden)

    Zhiyong Du

    Full Text Available OBJECTIVE: Elevated myocardial energy expenditure (MEE is related with reduced left ventricular ejection fraction, and has also been documented as an independent predictor of cardiovascular mortality. However, the serum small-molecule metabolite profiles and pathophysiological mechanisms of elevated MEE in heart failure (HF are still lacking. Herein, we used 1H-NMR-based metabolomics analysis to screen for potential biomarkers of MEE in HF. METHODS: A total of 61 subjects were enrolled, including 46 patients with heart failure and 15 age-matched controls. Venous serum samples were collected from subjects after an 8-hour fast. An INOVA 600 MHz nuclear magnetic resonance spectrometer with Carr-Purcell-Melboom-Gill (CPMG pulse sequence was employed for the metabolomics analysis and MEE was calculated using colored Doppler echocardiography. Metabolomics data were processed using orthogonal signal correction and regression analysis was performed using the partial least squares method. RESULTS: The mean MEE levels of HF patients and controls were 139.61±58.18 cal/min and 61.09±23.54 cal/min, respectively. Serum metabolomics varied with MEE changed, and 3-hydroxybutyrate, acetone and succinate were significantly elevated with the increasing MEE. Importantly, these three metabolites were independent of administration of angiotensin converting enzyme inhibitor, β-receptor blockers, diuretics and statins (P>0.05. CONCLUSIONS: These results suggested that in patients with heart failure, MEE elevation was associated with significant changes in serum metabolomics profiles, especially the concentration of 3-hydroxybutyrate, acetone and succinate. These compounds could be used as potential serum biomarkers to study myocardial energy mechanism in HF patients.

  5. Short-term toxicity assessments of an antibiotic metabolite in Wistar rats and its metabonomics analysis by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry

    International Nuclear Information System (INIS)

    Han, Hongxing; Xiao, Hailong; Lu, Zhenmei

    2016-01-01

    4-Epi-oxytetracycline (4-EOTC), one of main oxytetracycline (OTC) metabolites, can be commonly detected in food and environment. The toxicity and effects of OTC on animals have been well characterized; however, its metabolites have never been studied systemically. This study aims to investigate 15-day oral dose toxicity and urine metabonomics changes of 4-EOTC after repeated administration in Wistar rats at daily doses of 0.5, 5.0 and 50.0 mg/kg bw (bodyweight). Hematology and clinical chemistry parameters, including white blood cell count, red blood cell count, total protein, globulin and albumin/globulin, were obviously altered in rats of 5.0 and 50.0 mg/kg bw. Histopathology changes of kidney and liver tissues were also observed in high-dose groups. Urinary metabolites from all groups were analyzed using ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Seventeen metabolites contributing to the clusters were identified as potential biomarkers from multivariate analysis, including aminoadipic acid, 6-phosphogluconate, sebacic acid, pipecolic acid, etc. The significant changes of these biomarkers demonstrated metabonomic variations in treated rats, especially lysine and purine metabolism. For the first time in this paper, we combined the results of toxicity and metabonomics induced by 4-EOTC for the serious reconsideration of the safety and potential risks of antibiotics and its degradation metabolites. - Highlights: • 4-Epioxytetracycline (4-EOTC) induced damages in liver and kidney. • Metabonomics changes especially amino acid and purine metabolism were observed. • Security of OTC metabolite 4-EOTC should be taken into serious reconsideration.

  6. Technology insight: metabonomics in gastroenterology-basic principles and potential clinical applications

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Nielsen, Ole H; Wang, Yulan L

    2008-01-01

    successfully to the study of human diseases, toxicology, microbes, nutrition, and plant biology. This Review introduces the basic principles of nuclear magnetic resonance spectroscopy and commonly used tools for multivariate data analysis, before considering the applications and future potential....... Metabonomics, especially when based on nuclear magnetic resonance spectroscopy, has the potential to identify biomarkers and prognostic factors, enhance clinical diagnosis, and expand hypothesis generation. As a consequence, the use of metabonomics has been extensively explored in the past decade, and applied...... of metabonomics in basic and clinical research, with emphasis on applications in the field of gastroenterology....

  7. Metabonomic profiling of renal cell carcinoma: High-resolution proton nuclear magnetic resonance spectroscopy of human serum with multivariate data analysis

    International Nuclear Information System (INIS)

    Gao Hongchang; Dong Baijun; Liu Xia; Xuan Hanqing; Huang Yiran; Lin Donghai

    2008-01-01

    Metabonomic profiling using proton nuclear magnetic resonance ( 1 H NMR) spectroscopy and multivariate data analysis of human serum samples was used to characterize metabolic profiles in renal cell carcinoma (RCC). We found distinct, easily detectable differences between (a) RCC patients and healthy humans, (b) RCC patients with metastases and without metastases, and (c) RCC patients before and after nephrectomy. Compared to healthy human serum, RCC serum had higher levels of lipid (mainly very low-density lipoproteins), isoleucine, leucine, lactate, alanine, N-acetylglycoproteins, pyruvate, glycerol, and unsaturated lipid, together with lower levels of acetoacetate, glutamine, phosphatidylcholine/choline, trimethylamine-N-oxide, and glucose. This pattern was somewhat reversed after nephrectomy. Altered metabolite concentrations are most likely the result of the cells switching to glycolysis to maintain energy homeostasis following the loss of ATP caused by impaired TCA cycle in RCC. Serum NMR spectra combined with principal component analysis techniques offer an efficient, convenient way of depicting tumour biochemistry and stratifying tumours under different pathophysiological conditions. It may be able to assist early diagnosis and postoperative surveillance of human malignant diseases using single blood samples

  8. The toxicity of 3-chloropropane-1,2-dipalmitate in Wistar rats and a metabonomics analysis of rat urine by ultra-performance liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Li, Jianshuang; Wang, Sen; Wang, Maoqing; Shi, Wenxiu; Du, Xiaoyan; Sun, Changhao

    2013-11-25

    3-Monochloropropane-1,2-diol(3-MCPD) fatty acid esters can release free 3-MCPD in a certain condition. Free 3-MCPD is a well-known food contaminant and is toxicological well characterized, however, in contrast to free 3-MCPD, the toxicological characterization of 3-MCPD fatty acid esters is puzzling. In this study, toxicological and metabonomics studies of 3-chloropropane-1,2-dipalmitate(3-MCPD dipalmitate) were carried out based on an acute oral toxicity test, a 90-day feeding test and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. The LD50 value of 3-MCPD dipalmitate was determined to be 1780 mg/kg body weight (bw) for Wistar rats. The results of the 90-day feeding test in male Wistar rats showed that 3-MCPD dipalmitate caused a significant increase in blood urea nitrogen and creatinine in the high-dose group (267 mg/kg bw/day) compared to control rats. Renal tubular epithelium cell degeneration and renal tubular hyaline cast accumulation were the major histopathological changes in rats administered 3-MCPD dipalmitate. Urine samples obtained after the 90-day feeding test and analyzed by UPLC-MS showed that the differences in metabolic profiles between control and treated rats were clearly distinguished by partial least squares-discriminant analysis (PLS-DA) of the chromatographic data. Five metabolite biomarkers which had earlier and significant variations had been identified, they were first considered to be the early, sensitive biomarkers in evaluating the effect of 3-MCPD dipalmitate exposure, and the possible mechanism of these biomarkers variation was elucidated. The combination of histopathological examination, clinical chemistry and metabolomics analyses in rats resulted in a systematic and comprehensive assessment of the long-term toxicity of 3-MCPD dipalmitate. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  9. Metabonomic analysis of the joint toxic action of long-term low-level exposure to a mixture of four organophosphate pesticides in rat plasma.

    Science.gov (United States)

    Du, Longfei; Li, Sifan; Qi, Lei; Hou, Yurong; Zeng, Yan; Xu, Wei; Wang, Hong; Zhao, Xiujuan; Sun, Changhao

    2014-05-01

    In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) in rats using metabonomic technology at their corresponding no observed adverse effect levels (NOAELs). The results show that a single pesticide did not elicit a toxic response. The joint toxic action of four pesticides (at their corresponding NOAELs) was evaluated by metabolomic analysis of rat plasma under experimental conditions similar to those of the four single OP pesticides. The pesticides were administered daily to rats through drinking water for 24 weeks. The mixture of four pesticides showed a joint toxic action at the NOAELs of each pesticide. The 19 metabolites were statistically significantly changed in all the treated groups compared with those in the control group (p pesticides resulted in increased lysoPC (15 : 0/0 : 0), lysoPC (16 : 0/0 : 0), lysoPC (O-18 : 0/0 : 0), lysoPC (P-19 : 1(12Z)/0 : 0), lysoPC (18 : 1(9Z)/0 : 0), lysoPC (18 : 0/0 : 0), lysoPC (20 : 4(5Z, 8Z, 11Z, 14Z)/0 : 0), lysoPE (16 : 0/0 : 0), lysoPC (17 : 0/0 : 0), 4-pyridoxic acid, glutamic acid, glycocholic acid, and arachidonic acid, as well as decreased C16 sphinganine, C17 sphinganine, phytosphingosine, indoleacrylic acid, tryptophan, and iodotyrosine in rat plasma. The results indicate that the mixture of OP pesticides induced oxidative stress, liver and renal dysfunction, disturbed the metabolism of lipids and amino acids, and interfered with the function of the thyroid gland. The present plasma results provided complementarities with our previous metabolomic analysis of the rat urine profile exposed to a mixture of four OP pesticides, and also contributed to the understanding of the mechanism of joint toxic action.

  10. Metabonomics in neonatal nutrition research

    Directory of Open Access Journals (Sweden)

    Serge Rezzi

    2015-10-01

    Full Text Available Maternal obesity and early post-natal nutrition might associate with increased obesity risk in later life. We have investigated the effect of breastfeeding and infant formulas differing in protein content on the urinary and fecal metabolism of term infants born from overweight and obese mothers using a metabonomic approach. Metabolic differences were observed between breast and formula fed infants both in urine and stool samples. Metabolic profiles of formula fed infants exhibited a distinct metabolic pattern that was associated with the processing of dietary proteins from the host and the gut microbiota. Metabonomics appears as a powerful tool to measure the physiological response to infant formula versus the gold standard breastfeeding. In future, nutritional phenotyping will combine metabonomics and nutritional profiling to study specific nutritional requirements and measure the efficacy of tailored nutritional interventions on growth and development endpoints. It will then open novel opportunities to develop targeted nutritional solutions for health maintenance and disease prevention. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the Netherlands, Gavino Faa (Cagliari, Italy, Antonio Giordano (Philadelphia, USA

  11. Metabonomics for detection of nuclear materials processing

    International Nuclear Information System (INIS)

    Alam, Todd Michael; Luxon, Bruce A.; Neerathilingam, Muniasamy; Ansari, S.; Volk, David; Sarkar, S.; Alam, Mary Kathleen

    2010-01-01

    Tracking nuclear materials production and processing, particularly covert operations, is a key national security concern, given that nuclear materials processing can be a signature of nuclear weapons activities by US adversaries. Covert trafficking can also result in homeland security threats, most notably allowing terrorists to assemble devices such as dirty bombs. Existing methods depend on isotope analysis and do not necessarily detect chronic low-level exposure. In this project, indigenous organisms such as plants, small mammals, and bacteria are utilized as living sensors for the presence of chemicals used in nuclear materials processing. Such 'metabolic fingerprinting' (or 'metabonomics') employs nuclear magnetic resonance (NMR) spectroscopy to assess alterations in organismal metabolism provoked by the environmental presence of nuclear materials processing, for example the tributyl phosphate employed in the processing of spent reactor fuel rods to extract and purify uranium and plutonium for weaponization.

  12. Identification of sex-specific urinary biomarkers for major depressive disorder by combined application of NMR- and GC?MS-based metabonomics

    OpenAIRE

    Zheng, P; Chen, J-J; Zhou, C-J; Zeng, L; Li, K-W; Sun, L; Liu, M-l; Zhu, D; Liang, Z-H; Xie, P

    2016-01-01

    Women are more vulnerable to major depressive disorder (MDD) than men. However, molecular biomarkers of sex differences are limited. Here we combined gas chromatography?mass spectrometry (GC?MS)- and nuclear magnetic resonance (NMR)-based metabonomics to investigate sex differences of urinary metabolite markers in MDD, and further explore their potential of diagnosing MDD. Consequently, the metabolite signatures of women and men MDD subjects were significantly different from of that in their ...

  13. [Primary anylasis on the methodology and strategies for studying mechanisms of acu-moxibustion by using metabonomics].

    Science.gov (United States)

    Gao, Jun; Liu, Xu-guang; Yan, Xian-zhong; Yu, Shu-guang; Wu, Qiao-feng; Du, Huai-bin; Liang, Fan-rang

    2011-08-01

    Metabonomics is a newly emerging modern technology in the Post-genome era and has been being used widely in the study on modern Chinese medicine. But it have been rarely used in the study on acupuncture therapy. In the present paper, the authors introduce the unique advantages of metabonomics in the systemtic biology and its widespread studying basis in the field of modern Chinese medicine. Metabonomics and Chinese medicine including acupuncturology are of some similar characteristics such as entirety, comprehensiveness and dynamic changes. Moreover, the authors make a primary discussion and strategic analysis on the key issues of researches about sham acupuncture, chrono-acupuncture, mechanisms of acu-moxibustion underlying improvement of clinical severe disorders and various indications problems, regularities of combination of acupoints in different recipes, etc. by using metabonomics.

  14. NMR-based metabolomics applications

    DEFF Research Database (Denmark)

    Iaccarino, Nunzia

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

  15. Early Effect of Amyloid β-Peptide on Hippocampal and Serum Metabolism in Rats Studied by an Integrated Method of NMR-Based Metabolomics and ANOVA-Simultaneous Component Analysis

    Directory of Open Access Journals (Sweden)

    Yao Du

    2017-01-01

    Full Text Available Amyloid β (Aβ deposition has been implicated in the pathogenesis of Alzheimer’s disease. However, the early effect of Aβ deposition on metabolism remains unclear. In the present study, thus, we explored the metabolic changes in the hippocampus and serum during first 2 weeks of Aβ25–35 injection in rats by using an integrated method of NMR-based metabolomics and ANOVA-simultaneous component analysis (ASCA. Our results show that Aβ25–35 injection, time, and their interaction had statistically significant effects on the hippocampus and serum metabolome. Furthermore, we identified key metabolites that mainly contributed to these effects. After Aβ25–35 injection from 1 to 2 weeks, the levels of lactate, N-acetylaspartate, creatine, and taurine were decreased in rat hippocampus, while an increase in lactate and decreases in LDL/VLDL and glucose were observed in rat serum. Therefore, we suggest that the reduction in energy and lipid metabolism as well as an increase in anaerobic glycolysis may occur at the early stage of Aβ25–35 deposition.

  16. Urinary NMR-based metabolomic analysis of rats possessing variable sperm count following orally administered Eurycoma longifolia extracts of different quassinoid levels.

    Science.gov (United States)

    Ebrahimi, Forough; Ibrahim, Baharudin; Teh, Chin-Hoe; Murugaiyah, Vikneswaran; Chan, Kit-Lam

    2016-04-22

    Eurycoma longifolia (Tongkat Ali, TA) roots have been ethnically used as a remedy to boost male sexual desire, libido, energy and fertility. The study evaluated the effect of TA extracts with different quassinoid levels on rats sperm count and examined corresponding post-treatment urinary metabolic changes. Twenty-four male Sprague-Dawley rats, categorized into 4 groups of 6 rats each, were orally administered for 48 days with water for the control (group 1), 125mg/kg of TA water extract (TAW, group 2), 125mg/kg of TA quassinoid-poor extract (TAQP, group 3) and 21mg/kg of TA quassinoid-rich extract (TAQR, group 4). Upon completion of the 48-day treatment, the urine samples were analyzed by NMR and the animals were subsequently sacrificed for sperm count analysis. The urine profiles were categorized according to sperm count level. The results showed that the sperm count in TAW- and TAQR-treated groups was significantly higher compared to the TAQP-administered and control groups. The orthogonal partial least squares discriminant analysis (OPLS-DA) model indicated a clear separation among the urine profiles with respect to sperm count level. Urine (1)H-NMR profiles of the high-sperm count group contained higher concentrations of trigonelline, alanine, benzoic acid and higher intensity of a signal at 3.42ppm, while ethanol was at higher concentration in the normal-sperm count group. The results proved the efficacy of quassinoids on sperm count increase in rats and provided quantitative markers in urine suitable for analysis of sperm profile and male fertility status. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  17. NMR-based approach to the analysis of radiopharmaceuticals: radiochemical purity, specific activity, and radioactive concentration values by proton and tritium NMR spectroscopy.

    Science.gov (United States)

    Schenk, David J; Dormer, Peter G; Hesk, David; Pollack, Scott R; Lavey, Carolee Flader

    2015-06-15

    Compounds containing tritium are widely used across the drug discovery and development landscape. These materials are widely utilized because they can be efficiently synthesized and produced at high specific activity. Results from internally calibrated (3)H and (1)H nuclear magnetic resonance (NMR) spectroscopy suggests that at least in some cases, this calibrated approach could supplement or potentially replace radio-high-performance liquid chromatography for radiochemical purity, dilution and scintillation counting for the measurement of radioactivity per volume, and liquid chromatography/mass spectrometry analysis for the determination of specific activity. In summary, the NMR-derived values agreed with those from the standard approaches to within 1% to 9% for solution count and specific activity. Additionally, the NMR-derived values for radiochemical purity deviated by less than 5%. A benefit of this method is that these values may be calculated at the same time that (3)H NMR analysis provides the location and distribution of tritium atoms within the molecule. Presented and discussed here is the application of this method, advantages and disadvantages of the approach, and a rationale for utilizing internally calibrated (1)H and (3)H NMR spectroscopy for specific activity, radioactive concentration, and radiochemical purity whenever acquiring (3)H NMR for tritium location. Copyright © 2015 John Wiley & Sons, Ltd.

  18. Metabonomics identifies serum metabolite markers of colorectal cancer.

    Science.gov (United States)

    Tan, Binbin; Qiu, Yunping; Zou, Xia; Chen, Tianlu; Xie, Guoxiang; Cheng, Yu; Dong, Taotao; Zhao, Linjing; Feng, Bo; Hu, Xiaofang; Xu, Lisa X; Zhao, Aihua; Zhang, Menghui; Cai, Guoxiang; Cai, Sanjun; Zhou, Zhanxiang; Zheng, Minhua; Zhang, Yan; Jia, Wei

    2013-06-07

    Recent studies suggest that biofluid-based metabonomics may identify metabolite markers promising for colorectal cancer (CRC) diagnosis. We report here a follow-up replication study, after a previous CRC metabonomics study, aiming to identify a distinct serum metabolic signature of CRC with diagnostic potential. Serum metabolites from newly diagnosed CRC patients (N = 101) and healthy subjects (N = 102) were profiled using gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS). Differential metabolites were identified with statistical tests of orthogonal partial least-squares-discriminant analysis (VIP > 1) and the Mann-Whitney U test (p partial least-squares-discriminant analysis (OPLS-DA) in a learning sample set of 62 CRC patients and 62 matched healthy controls. This established model was able to correctly assign the rest of the samples to the CRC or control groups in a validation set of 39 CRC patients and 40 healthy controls. Consistent with our findings from the previous study, we observed a distinct metabolic signature in CRC patients including tricarboxylic acid (TCA) cycle, urea cycle, glutamine, fatty acids, and gut flora metabolism. Our results demonstrated that a panel of serum metabolite markers is of great potential as a noninvasive diagnostic method for the detection of CRC.

  19. Discrimination of wild types and hybrids of Duboisia myoporoides and Duboisia leichhardtii at different growth stages using1H NMR-based metabolite profiling and tropane alkaloids-targeted HPLC-MS analysis.

    Science.gov (United States)

    Ullrich, Sophie Friederike; Averesch, Nils J H; Castellanos, Leonardo; Choi, Young Hae; Rothauer, Andreas; Kayser, Oliver

    2016-11-01

    Duboisia species, which belong to the family of Solanaceae, are commercially cultivated in large scale, as they are main source of the pharmaceutically-used active compound scopolamine. In this study, 1 H NMR-based metabolite profiling linking primary with secondary metabolism and additional quantification via HPCL-MS with special focus on the tropane alkaloids were applied to compare leaf and root extracts of three wild types and two hybrids of Duboisia myoporoides and D. leichhardtii at different developmental stages grown under controlled conditions in climate chambers and under agricultural field plantation. Based on the leaf extracts, a clear distinction between the Duboisia hybrids and the wild types Duboisia myoporoides and D. leichhardtii using principal component analysis of 1 H NMR data was observed. The average content in scopolamine in the hybrids of Duboisia cultivated in climate chambers increased significantly from month 3-6 after potting of the rooted cuttings, however not so for the examined wild types. The Duboisia hybrids grown in climate chambers showed higher growth and contained more sugars and amino acids than Duboisia hybrids grown in the field, which in contrast showed an enhanced flux towards tropane alkaloids as well as flavonoids. For a more detailed analysis of tropane alkaloids, an appropriate HPLC-MS method was developed and validated. The measurements revealed large differences in the alkaloid pattern within the different genotypes under investigation, especially regarding the last enzymatic step, the conversion from hyoscamine to scopolamine by the hyoscyamine 6β-hydroxylase. Scopolamine was found in highest concentrations in Duboisia hybrids (20.04 ± 4.05 and 17.82 ± 3.52 mg/g dry wt) followed by Duboisia myoporoides (12.71 ± 2.55 mg/g dry wt), both showing a high selectivity for scopolamine in contrast to Duboisia leichhardtii (3.38 ± 0.59 and 5.09 ± 1.24 mg/g dry wt) with hyoscyamine being the

  20. NMR-based metabonomics approaches for the assessment of the metabolic impact of dietary polyphenols on humans

    NARCIS (Netherlands)

    van Duynhoven, J.; van Velzen, E.; Gross, G.; van Dorsten, F.; Jacobs, D.; Bingham, M.; Draijer, R.; Mulder, T.; Koning, T.; Vaughan, E.; van der Wiele, T.; Westerhuis, J.; Smilde, A.

    2009-01-01

    Dietary polyphenols, as present in for example tea, fruit and vegetables, are associated with several beneficial health effects. Most evidence is still based on epidemiological studies. So far, most nutritional intervention studies on dietary polyphenols are directly focused on pre-identified

  1. Application of NMR-based metabonomics suggests a relationship between betaine absorption and elevated creatine plasma concentrations in catheterised sows

    DEFF Research Database (Denmark)

    Yde, Christian Clement; Westerhuis, Johan A.; Bertram, Hanne Christine S.

    2012-01-01

    of these metabolites from the small intestine. The LF diet resulted in a higher betaine concentration in the blood than the two high-fibre diets (P¼0·008). This leads to higher plasma concentrations of methionine (P¼0·0028) and creatine (P¼0·020) of endogenous origin. In conclusion, the use of NMR spectroscopy...... for measuring nutrient uptake in the present study elucidated the relationship between betaine uptake and elevated creatine plasma concentrations....

  2. Response of chronic gingivitis to hygiene therapy and experimental gingivitis. Clinical, microbiological and metabonomic changes.

    Science.gov (United States)

    Klukowska, Malgorzata; Goyal, C Ram; Khambe, Deepa; Cannon, Michael; Miner, Melanie; Gurich, Nataliya; Circello, Ben; Huggins, Tom; Barker, Matthew L; Furnish, Carrie; Conde, Erinn; Hoke, Phyllis; Haught, Chris; Xie, Sancai; White, Donald J

    2015-10-01

    To compare the clinical, microbiological and metabonomic profiles of subjects with high and low levels of chronic gingival bleeding during a controlled oral hygiene regimen intervention including sequential phases of rigorous therapeutic oral hygiene followed by experimental gingivitis (EG). Two cohorts of qualified study subjects with differences in gingival bleeding on probing levels at their baseline clinical examination were entered into the study. These two cohorts were followed through three separate study phases including a 1-week baseline phase, a 2-week phase of rigorous oral hygiene including dental prophylaxis, and a 3-week EG phase of no oral hygiene to encourage relapse of gingivitis. The 58 subjects were assessed during each phase of the study for clinical presentation of gingivitis and concurrently had plaque sampled for real-time polymerase chain reaction (RTPCR) microbiological characterization and salivary lavage samples for 'systems biology' metabonomics assessment by 1H-NMR. Subjects presenting with different levels of gingival bleeding on probing when they entered the study responded differently to rigorous oral hygiene and EG. Specifically, the high bleeding cohort responded sluggishly to rigorous oral hygiene and exhibited markedly greater relapse to gingivitis during EG. RTPCR analysis showed changes in bacterial populations that were associated with study phases, particularly the increases in putative periodontal pathogens during EG. However, the microbiological profiles of high- and low-susceptibility gingival bleeding patients were largely similar. Metabonomic analysis likewise revealed significant changes in metabolite composition during study phases associated with differences in plaque toxicity, especially the short chain carboxylic acids propionate and n-butyrate, which tracked clinical changes in gingivitis severity. Systems analysis of metabonomic changes suggested differences between cohorts, although analysis to date has not

  3. Application of metabonomic analytical techniques in the modernization and toxicology research of traditional Chinese medicine.

    Science.gov (United States)

    Lao, Yong-Min; Jiang, Jian-Guo; Yan, Lu

    2009-08-01

    In the recent years, a wide range of metabonomic analytical techniques are widely used in the modern research of traditional Chinese medicine (TCM). At the same time, the international community has attached increasing importance to TCM toxicity problems. Thus, many studies have been implemented to investigate the toxicity mechanisms of TCM. Among these studies, many metabonomic-based methods have been implemented to facilitate TCM toxicity investigation. At present, the most prevailing methods for TCM toxicity research are mainly single analysis techniques using only one analytical means. These techniques include nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), etc.; with these techniques, some favourable outcomes have been gained in the toxic reaction studies of TCM, such as the action target organs assay, the establishment of action pattern, the elucidation of action mechanism and the exploration of action material foundation. However, every analytical technique has its advantages and drawbacks, no existing analytical technique can be versatile. Multi-analysed techniques can partially overcome the shortcomings of single-analysed techniques. Combination of GC-MS and LC-MS metabolic profiling approaches has unravelled the pathological outcomes of aristolochic acid-induced nephrotoxicity, which can not be achieved by single-analysed techniques. It is believed that with the further development of metabonomic analytical techniques, especially multi-analysed techniques, metabonomics will greatly promote TCM toxicity research and be beneficial to the modernization of TCM in terms of extending the application of modern means in the TCM safety assessment, assisting the formulation of TCM safety norms and establishing the international standards indicators.

  4. Correlations of Fecal Metabonomic and Microbiomic Changes Induced by High-fat Diet in the Pre-Obesity State

    Science.gov (United States)

    Lin, Hong; An, Yanpeng; Hao, Fuhua; Wang, Yulan; Tang, Huiru

    2016-02-01

    Obesity resulting from interactions of genetic and environmental factors becomes a serious public health problem worldwide with alterations of the metabolic phenotypes in multiple biological matrices involving multiple metabolic pathways. To understand the contributions of gut microbiota to obesity development, we analyzed dynamic alterations in fecal metabonomic phenotype using NMR and fecal microorganism composition in rats using pyrosequencing technology during the high-fat diet (HFD) feeding for 81 days (pre-obesity state). Integrated analysis of these two phenotypic datasets was further conducted to establish correlations between the altered rat fecal metabonome and gut microbiome. We found that one-week HFD feeding already caused significant changes in rat fecal metabonome and such changes sustained throughout 81-days feeding with the host and gut microbiota co-metabolites clearly featured. We also found that HFD caused outstanding decreases in most fecal metabolites implying enhancement of gut absorptions. We further established comprehensive correlations between the HFD-induced changes in fecal metabonome and fecal microbial composition indicating contributions of gut microbiota in pathogenesis and progression of the HFD-induced obesity. These findings provided essential information about the functions of gut microbiota in pathogenesis of metabolic disorders which could be potentially important for developing obesity prevention and treatment therapies.

  5. Metabonomic profiling: a novel approach in neuroendocrine neoplasias.

    Science.gov (United States)

    Kinross, James M; Drymousis, Panagiotis; Jiménez, Beatriz; Frilling, Andrea

    2013-12-01

    A metabonomic phenotyping strategy was developed as part of a pilot study to define a diagnostic metabolic phenotype for neuroendocrine neoplasms (NEN). Twenty-eight patients with NEN were prospectively recruited: small bowel NEN, n = 8; pancreatic NEN, n = 10; and others, n = 10 (mean age 49.4 years [26–81] male/female ratio 17:11). There were 17 healthy control patients. Urine samples were subjected to 1H nuclear magnetic resonance spectroscopic profiling via the use of a Bruker Avance 600-MHz spectrometer (Bruker, Rheinstetten, Germany). Acquired spectral data were imported into SIMCA and MATLAB for supervised and unsupervised multivariate analysis. Partial least squares-discriminant analysis differentiated between NEN and healthy samples with accuracy (R(2)Y = 0.79, Q2Y = 0.53, area under the curve [AUC] 0.90). Orthogonal partial least squares-discriminant analysis was able to distinguish between small bowel NEN and pancreatic NEN (R2Y = 0.91, Q2Y = 0.35). Subclass analysis also demonstrated class separation between functional and nonfunctional NEN (R2Y = 0.98, Q2Y = 0.77, AUC 0.6) and those with metastases (R2Y = 0.72 , Q2 Y = 0.41, AUC 0.86) due to variations in hippurate metabolism (P analysis suggests that subgroups of NEN may possess a stratified metabolic phenotype. Metabolic profiling could provide novel biomarkers for NEN.

  6. NMR-based screening of membrane protein ligands

    NARCIS (Netherlands)

    Yanamala, Naveena; Dutta, Arpana; Beck, Barbara; Van Fleet, Bart; Hay, Kelly; Yazbak, Ahmad; Ishima, Rieko; Doemling, Alexander; Klein-Seetharaman, Judith

    2010-01-01

    Membrane proteins pose problems for the application of NMR-based ligand-screening methods because of the need to maintain the proteins in a membrane mimetic environment such as detergent micelles: they add to the molecular weight of the protein, increase the viscosity of the solution, interact with

  7. Altered metabolism of growth hormone receptor mutant mice: a combined NMR metabonomics and microarray study.

    Directory of Open Access Journals (Sweden)

    Horst Joachim Schirra

    Full Text Available BACKGROUND: Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signalling in mutant mice that have truncations at position 569 and 391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum or no growth hormone-dependent STAT5 signalling respectively. These mutations result in altered liver metabolism, obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: The analysis of metabolic changes was performed using microarray analysis of liver tissue and NMR metabonomics of urine and liver tissue. Data were analyzed using multivariate statistics and Gene Ontology tools. The metabolic profiles characteristic for each of the two mutant groups and wild-type mice were identified with NMR metabonomics. We found decreased urinary levels of taurine, citrate and 2-oxoglutarate, and increased levels of trimethylamine, creatine and creatinine when compared to wild-type mice. These results indicate significant changes in lipid and choline metabolism, and were coupled with increased fat deposition, leading to obesity. The microarray analysis identified changes in expression of metabolic enzymes correlating with alterations in metabolite concentration both in urine and liver. Similarity of mutant 569 to the wild-type was seen in young mice, but the pattern of metabolites shifted to that of the 391 mutant as the 569 mice became obese after six months age. CONCLUSIONS/SIGNIFICANCE: The metabonomic observations were consistent with the parallel analysis of gene expression and pathway mapping using microarray data, identifying metabolites and gene transcripts involved in hepatic metabolism, especially for taurine, choline and creatinine metabolism. The systems biology approach applied in this study provides a coherent picture of metabolic changes resulting from impaired STAT5 signalling by the growth hormone

  8. Application of nuclear magnetic resonance spectroscopy combined with principal component analysis in detecting inborn errors of metabolism using blood spots: a metabonomic approach

    International Nuclear Information System (INIS)

    Constantinou, M.A.; Papakonstantinou, E.; Benaki, D.; Spraul, M.; Shulpis, K.; Koupparis, M.A.; Mikros, E.

    2004-01-01

    NMR spectra of extracted blood spots were used to investigate the possibility for the development of a new method for mass screening concerning the diagnosis of inborn errors of metabolism (IEM). Blood spots were collected on filter papers from normal, phenylketonuric (PKU) and maple syrup urine disease (MSUD) subjects and their Carr-Purcell-Meiboom-Gill (CPMG) 1 H NMR spectra were acquired. The spectra were reduced to a number of spectral descriptors and principal component analysis (PCA) was performed. The scores plot showed that PKU and MSUD samples were well discriminated from the main cluster of points

  9. Biomarkers identified by urinary metabonomics for noninvasive diagnosis of nutritional rickets.

    Science.gov (United States)

    Wang, Maoqing; Yang, Xue; Ren, Lihong; Li, Songtao; He, Xuan; Wu, Xiaoyan; Liu, Tingting; Lin, Liqun; Li, Ying; Sun, Changhao

    2014-09-05

    Nutritional rickets is a worldwide public health problem; however, the current diagnostic methods retain shortcomings for accurate diagnosis of nutritional rickets. To identify urinary biomarkers associated with nutritional rickets and establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis were employed to investigate the metabolic alterations associated with nutritional rickets in 200 children with or without nutritional rickets. The pathophysiological changes and pathogenesis of nutritional rickets were illustrated by the identified biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets were identified and five candidate biomarkers for clinical diagnosis were screened and identified by quantitative analysis and receiver operating curve analysis. Urinary levels of five candidate biomarkers were measured using mass spectrometry or commercial kits. In the validation step, the combination of phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis of the pathway analysis of biomarkers, our urinary metabonomics analysis gives new insight into the pathogenesis and pathophysiology of nutritional rickets.

  10. Identification of sex-specific urinary biomarkers for major depressive disorder by combined application of NMR- and GC-MS-based metabonomics.

    Science.gov (United States)

    Zheng, P; Chen, J-J; Zhou, C-J; Zeng, L; Li, K-W; Sun, L; Liu, M-L; Zhu, D; Liang, Z-H; Xie, P

    2016-11-15

    Women are more vulnerable to major depressive disorder (MDD) than men. However, molecular biomarkers of sex differences are limited. Here we combined gas chromatography-mass spectrometry (GC-MS)- and nuclear magnetic resonance (NMR)-based metabonomics to investigate sex differences of urinary metabolite markers in MDD, and further explore their potential of diagnosing MDD. Consequently, the metabolite signatures of women and men MDD subjects were significantly different from of that in their respective healthy controls (HCs). Twenty seven women and 36 men related differentially expressed metabolites were identified in MDD. Fourteen metabolites were changed in both women and men MDD subjects. Significantly, the women-specific (m-Hydroxyphenylacetate, malonate, glycolate, hypoxanthine, isobutyrate and azelaic acid) and men-specific (tyrosine, N-acetyl-d-glucosamine, N-methylnicotinamide, indoxyl sulfate, citrate and succinate) marker panels were further identified, which could differentiate men and women MDD patients from their respective HCs with higher accuracy than previously reported sex-nonspecific marker panels. Our findings demonstrate that men and women MDD patients have distinct metabonomic signatures and sex-specific biomarkers have promising values in diagnosing MDD.

  11. Identification of sex-specific urinary biomarkers for major depressive disorder by combined application of NMR- and GC–MS-based metabonomics

    Science.gov (United States)

    Zheng, P; Chen, J-J; Zhou, C-J; Zeng, L; Li, K-W; Sun, L; Liu, M-l; Zhu, D; Liang, Z-H; Xie, P

    2016-01-01

    Women are more vulnerable to major depressive disorder (MDD) than men. However, molecular biomarkers of sex differences are limited. Here we combined gas chromatography–mass spectrometry (GC–MS)- and nuclear magnetic resonance (NMR)-based metabonomics to investigate sex differences of urinary metabolite markers in MDD, and further explore their potential of diagnosing MDD. Consequently, the metabolite signatures of women and men MDD subjects were significantly different from of that in their respective healthy controls (HCs). Twenty seven women and 36 men related differentially expressed metabolites were identified in MDD. Fourteen metabolites were changed in both women and men MDD subjects. Significantly, the women-specific (m-Hydroxyphenylacetate, malonate, glycolate, hypoxanthine, isobutyrate and azelaic acid) and men-specific (tyrosine, N-acetyl-d-glucosamine, N-methylnicotinamide, indoxyl sulfate, citrate and succinate) marker panels were further identified, which could differentiate men and women MDD patients from their respective HCs with higher accuracy than previously reported sex-nonspecific marker panels. Our findings demonstrate that men and women MDD patients have distinct metabonomic signatures and sex-specific biomarkers have promising values in diagnosing MDD. PMID:27845778

  12. Probing gender-specific metabolism differences in humans by nuclear magnetic resonance-based metabonomics.

    Science.gov (United States)

    Kochhar, Sunil; Jacobs, Doris M; Ramadan, Ziad; Berruex, France; Fuerholz, Andreas; Fay, Laurent B

    2006-05-15

    The measurement of metabolite profiles that are interpreted to yield biomarkers using multivariate data analysis is now a well-established approach for gaining an improved understanding of the impact of genetic modifications, toxicological and therapeutic interventions, and exposure to stimuli (e.g., noxious agents, stressors, nutrients) on the network of transcripts, proteins, and metabolites present in cells, tissues, or whole organisms. This has been termed metabonomics. In this study, multivariate analysis of (1)H nuclear magnetic resonance (NMR) spectra of metabolite profiles of urine and plasma from 150 healthy humans revealed that in young people and/or individuals with low body mass indexes, females had higher rates of lipid biosynthesis than did males, whereas males had higher rates of protein turnover than did females. With increasing age, overall lipid biosynthesis decreased in females, whereas metabolism increasingly favored lipid synthesis over protein turnover in males. By relating the derived metabonomic data to known metabolic pathways and published biochemical data, it appears that females synthesize relatively more lipoproteins and unsaturated lipids than do males. Furthermore, the changes in lipid biosynthesis and urinary citrate excretion in females showed a positive correlation. Estrogen most likely plays an essential role in the regulation of, and communication between, protein and lipid biosynthesis by controlling pH in mitochondria and the cytoplasm and hence the observed altered citrate levels.

  13. A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion.

    Science.gov (United States)

    Wang, Yulan; Tang, Huiru; Nicholson, Jeremy K; Hylands, Peter J; Sampson, J; Holmes, Elaine

    2005-01-26

    A metabonomic strategy, utilizing high-resolution 1H NMR spectroscopy in conjunction with chemometric methods (discriminant analysis with orthogonal signal correction), has been applied to the study of human biological responses to chamomile tea ingestion. Daily urine samples were collected from volunteers during a 6-week period incorporating a 2-week baseline period, 2 weeks of daily chamomile tea ingestion, and a 2-week post-treatment phase. Although strong intersubject variation in metabolite profiles was observed, clear differentiation between the samples obtained before and after chamomile ingestion was achieved on the basis of increased urinary excretion of hippurate and glycine with depleted creatinine concentration. Samples obtained up to 2 weeks after daily chamomile intake formed an isolated cluster in the discriminant analysis map, from which it was inferred that the metabolic effects of chamomile ingestion were prolonged during the 2-week postdosing period. This study highlights the potential for metabonomic technology in the assessment of nutritional interventions, despite the high degree of variation from genetic and environmental sources.

  14. A metabonomic evaluation of the monocrotaline-induced sinusoidal obstruction syndrome (SOS) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Conotte, R.; Colet, J.-M., E-mail: jean-marie.colet@umons.ac.be

    2014-04-15

    The main curative treatment of colorectal cancer remains the surgery. However, when metastases are suspected, surgery is followed by a preventive chemotherapy using oxaliplatin which, unfortunately, may cause liver sinusoidal obstruction syndrome (SOS). Such hepatic damage is barely detected during or after chemotherapy due to a lack of effective diagnostic procedures, but liver biopsy. The primary objective of the present study was to identify potential early diagnosis biomarkers of SOS using a metabonomic approach. SOS was induced in rats by monocrotaline, a prototypical toxic substance. {sup 1}H NMR spectroscopy analysis of urine samples collected from rats treated with monocrotaline showed significant metabolic changes as compared to controls. During a first phase, cellular protective mechanisms such as an increased synthesis of GSH (reduced taurine) and the recruitment of cell osmolytes in the liver (betaine) were seen. In the second phase, the disturbance of the urea cycle (increased ornithine and urea reduction) leading to the depletion of NO, the alteration in the GSH synthesis (increased creatine and GSH precursors (glutamate, dimethylglycine and sarcosine)), and the liver necrosis (decrease taurine and increase creatine) all indicate the development of SOS. - Highlights: • Urine metabonomic profiles of SOS have been identified. • Urine osmoprotectants and anti-oxidants indicated an initial liver protection. • Liver necrosis was demonstrated by increased urine levels of taurine and creatine. • NO depletion was suggested by changes in ornithine and urea.

  15. Application of NMR-based techniques in aquatic toxicology: brief examples.

    Science.gov (United States)

    Tjeerdema, Ronald S

    2008-01-01

    Nuclear magnetic resonance spectroscopy (NMR) has been employed over many years for the elucidation of chemical structures. However, in more recent years it has been used to characterize sublethal actions of pollutants in aquatic organisms. For instance, in vivo NMR involves live, intact organisms or cell cultures and the application of chemical stressors to reveal toxic mechanisms in real time. Alternatively, NMR-based metabolomics involves rapid cessation of metabolic activity following chemical exposure (via liquid N(2)) to provide an assessment of metabolic actions via more traditional NMR analysis. Two examples are briefly presented to exemplify the power of NMR for assessing toxic actions in marine and freshwater organisms.

  16. {sup 1}H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying; Lin, Lianjie [Second Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110004 (China); Xu, Yanbin [Wanlei Life Sciences (Shenyang) Co., Ltd., Shenyang 110179 (China); Lin, Yan; Jin, Yu [Second Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110004 (China); Zheng, Changqing, E-mail: changqing_zheng@126.com [Second Department of Gastroenterology, Shengjing Hospital, China Medical University, Shenyang 110004 (China)

    2013-04-19

    Highlights: •Twenty ulcerative colitis patients and nineteen healthy controls were enrolled. •Increased 3-hydroxybutyrate, glucose, phenylalanine, and decreased lipid were found. •We report early stage diagnosis of ulcerative colitis using NMR-based metabolomics. -- Abstract: Ulcerative colitis (UC) has seriously impaired the health of citizens. Accurate diagnosis of UC at an early stage is crucial to improve the efficiency of treatment and prognosis. In this study, proton nuclear magnetic resonance ({sup 1}H NMR)-based metabolomic analysis was performed on serum samples collected from active UC patients (n = 20) and healthy controls (n = 19), respectively. The obtained spectral profiles were subjected to multivariate data analysis. Our results showed that consistent metabolic alterations were present between the two groups. Compared to healthy controls, UC patients displayed increased 3-hydroxybutyrate, β-glucose, α-glucose, and phenylalanine, but decreased lipid in serum. These findings highlight the possibilities of NMR-based metabolomics as a non-invasive diagnostic tool for UC.

  17. A novel Bayesian approach to quantify clinical variables and to determine their spectroscopic counterparts in 1H NMR metabonomic data

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    Kaski Kimmo

    2007-05-01

    Full Text Available Abstract Background A key challenge in metabonomics is to uncover quantitative associations between multidimensional spectroscopic data and biochemical measures used for disease risk assessment and diagnostics. Here we focus on clinically relevant estimation of lipoprotein lipids by 1H NMR spectroscopy of serum. Results A Bayesian methodology, with a biochemical motivation, is presented for a real 1H NMR metabonomics data set of 75 serum samples. Lipoprotein lipid concentrations were independently obtained for these samples via ultracentrifugation and specific biochemical assays. The Bayesian models were constructed by Markov chain Monte Carlo (MCMC and they showed remarkably good quantitative performance, the predictive R-values being 0.985 for the very low density lipoprotein triglycerides (VLDL-TG, 0.787 for the intermediate, 0.943 for the low, and 0.933 for the high density lipoprotein cholesterol (IDL-C, LDL-C and HDL-C, respectively. The modelling produced a kernel-based reformulation of the data, the parameters of which coincided with the well-known biochemical characteristics of the 1H NMR spectra; particularly for VLDL-TG and HDL-C the Bayesian methodology was able to clearly identify the most characteristic resonances within the heavily overlapping information in the spectra. For IDL-C and LDL-C the resulting model kernels were more complex than those for VLDL-TG and HDL-C, probably reflecting the severe overlap of the IDL and LDL resonances in the 1H NMR spectra. Conclusion The systematic use of Bayesian MCMC analysis is computationally demanding. Nevertheless, the combination of high-quality quantification and the biochemical rationale of the resulting models is expected to be useful in the field of metabonomics.

  18. Recent developments in sample preparation and data pre-treatment in metabonomics research.

    Science.gov (United States)

    Li, Ning; Song, Yi peng; Tang, Huiru; Wang, Yulan

    2016-01-01

    Metabonomics is a powerful approach for biomarker discovery and an effective tool for pinpointing endpoint metabolic effects of external stimuli, such as pathogens and disease development. Due to its wide applications, metabonomics is required to deal with various biological samples of different properties. Hence sample preparation and corresponding data pre-treatment become important factors in ensuring validity of an investigation. In this review, we summarize some recent developments in metabonomics sample preparation and data-pretreatment procedures. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. 1H NMR-based metabolomics of time-dependent responses of Eisenia fetida to sub-lethal phenanthrene exposure

    International Nuclear Information System (INIS)

    Lankadurai, Brian P.; Wolfe, David M.; Simpson, Andre J.; Simpson, Myrna J.

    2011-01-01

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

  20. QGQS Granule in SHR Serum Metabonomics Study Based on Tools of UPLC-Q-TOF and Renin-Angiotensin-Aldosterone System Form Protein Profilin-1

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    Ke Li

    2017-01-01

    Full Text Available QGQS granule is effective for the therapeutic of hypertension in clinic. The aim of this research is to observe the antihypertension effect of QGQS granule on SHR and explain the mechanism of its lowering blood pressure. 30 SHR were selected as model group, captopril group, and QGQS group, 10 WKYr were used as control group, and RBP were measured on tail artery consciously. And all the serum sample analysis was carried out on UPLC-TOF-MS system to determine endogenous metabolites and to find the metabonomics pathways. Meanwhile, ELISA kits for the determination pharmacological indexes of PRA, AngI, AngII, and ALD were used for pathway confirmatory; WB for determination of profilin-1 protein expression was conducted for Ang II pathway analysis as well. It is demonstrated that QGQS granule has an excellent therapeutic effect on antihypertension, which exerts effect mainly on metabonomics pathway by regulating glycerophospholipid, sphingolipid, and arachidonic acid metabolism, and it could inhibit the overexpression of the profilin-1 protein. We can come to a conclusion that RAAS should be responsible mainly for the metabonomics pathway of QGQS granule on antihypertension, and it plays a very important role in protein of profilin-1 inhibition.

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

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2013-04-03

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

  2. Metabonomic Strategy to the Evaluation of Chinese Medicine Compound Danshen Dripping Pills Interfering Myocardial Ischemia in Rats

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    Xue Xin

    2013-01-01

    Full Text Available Coronary heart disease (CHD is one of the highest mortality diseases in the world. Traditional Chinese medicine compound Danshen dripping pills (CDDPs have currently made a great achievement in treating CHD. However, the therapeutic mechanism of CDDP is often poorly interpreted. In this study, a GC-MS-based metabonomic study was conducted to assess the holistic efficacy of CDDP for myocardial infarction in male Sprague-Dawley rats, which were divided into the control group, the sham group, the model group, the control + CDDP group, and the model + CDDP, with CDDP at a dose of 107 mg/kg·d (equal to 1.8 mL/kg·d. The metabonomic findings demonstrated great differences of metabolic pattern among sham, model, and the model + CDDP in the orthogonal partial least squares discriminant analysis (OPLS-DA models, which coordinated well with the assessment of plasma biochemistry and histopathological assay. Differentially expressed metabolites suggested that energy metabolism, glycolysis, and lipid metabolism might be disrupted by myocardial infarction. Both the potential metabolic biomarkers and the biochemical histopathological indices were regulated effectively by CDDP.

  3. [Monitoring of chemical components with different color traits of Tussilago farfara using NMR-based metabolomics].

    Science.gov (United States)

    Mi, Xi; Li, Zhen-yu; Qin, Xue-mei; Zhang, Li-zeng

    2013-11-01

    The quality and grade of traditional Chinese medicinal herbs were assessed by their characteristics traditionally. According to traditional experience, the quality of the purple Flos Farfarae is better than that of yellow buds. NMR-based metabolomic approach combined with significant analysis of microarray (SAM) and Spearman rank correlation analysis were used to investigate the different metabolites of the Flos Farfarae with different color feature. Principal component analysis (PCA) showed clear distinction between the purple and yellow flower buds of Tussilago farfara. The S-plot of orthogonal PLS-DA (OPLS-DA) and t test revealed that the levels of threonine, proline, phosphatidylcholine, creatinine, 4, 5-dicaffeoylquinic acid, rutin, caffeic acid, kaempferol analogues, and tussilagone were higher in the purple flower buds than that in the yellow buds, in agreement with the results of SAM and Spearman rank correlation analysis. The results confirmed the traditional medication experience that "purple flower bud is better than the yellow ones", and provide a scientific basis for assessing the quality of Flos Farfarae by the color features.

  4. 1H NMR metabonomics indicates continued metabolic changes and sexual dimorphism post-parasite clearance in self-limiting murine malaria model.

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    Arjun Sengupta

    Full Text Available Malaria, a mosquito-borne disease caused by Plasmodium spp. is considered to be a global threat, specifically for the developing countries. In human subjects considerable information exists regarding post-malarial physiology. However, most murine malarial models are lethal, and most studies deal with acute phases occurring as disease progresses. Much less is known regarding physiological status post-parasite clearance. We have assessed the physiological changes at the organ levels using (1H NMR based metabonomics in a non lethal self-clearing murine malarial model of P. chabaudi parasites and Balb/C, far beyond the parasite clearance point. The results showed distinct metabolic states between uninfected and infected mice at the peak parasitemia, as well as three weeks post-parasite clearance. Our data also suggests that the response at the peak infection as well as recovery exhibited distinct sexual dimorphism. Specifically, we observed accumulation of acetylcholine in the brain metabolic profile of both the sexes. This might have important implication in understanding the pathophysiology of the post malarial neurological syndromes. In addition, the female liver showed high levels of glucose, dimethylglycine, methylacetoacetate and histidine after three weeks post-parasite clearance, while the males showed accumulation of branched chain amino acids, lysine, glutamine and bile acids.

  5. UPLC-based metabonomic applications for discovering biomarkers of diseases in clinical chemistry.

    Science.gov (United States)

    Zhao, Ying-Yong; Cheng, Xian-Long; Vaziri, Nosratola D; Liu, Shuman; Lin, Rui-Chao

    2014-10-01

    Metabonomics is a powerful and promising analytic tool that allows assessment of global low-molecular-weight metabolites in biological systems. It has a great potential for identifying useful biomarkers for early diagnosis, prognosis and assessment of therapeutic interventions in clinical practice. The aim of this review is to provide a brief summary of the recent advances in UPLC-based metabonomic approach for biomarker discovery in a variety of diseases, and to discuss their significance in clinical chemistry. All the available information on UPLC-based metabonomic applications for discovering biomarkers of diseases were collected via a library and electronic search (using Web of Science, Pubmed, ScienceDirect, Springer, Google Scholar, etc.). Metabonomics has been used in clinical chemistry to identify and evaluate potential biomarkers and therapeutic targets in various diseases affecting the liver (hepatocarcinoma and liver cirrhosis), lung (lung cancer and pneumonia), gastrointestinal tract (colorectal cancer) and urogenital tract (prostate cancer, ovarian cancer and chronic kidney disease), as well as metabolic diseases (diabetes) and neuropsychiatric disorders (Alzheimer's disease and schizophrenia), etc. The information provided highlights the potential value of determination of endogenous low-molecular-weight metabolites and the advantages and potential drawbacks of the application of UPLC-based metabonomics in clinical setting. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  6. NMR-Based Identification of Metabolites in Polar and Non-Polar Extracts of Avian Liver.

    Science.gov (United States)

    Fathi, Fariba; Brun, Antonio; Rott, Katherine H; Falco Cobra, Paulo; Tonelli, Marco; Eghbalnia, Hamid R; Caviedes-Vidal, Enrique; Karasov, William H; Markley, John L

    2017-11-16

    Metabolites present in liver provide important clues regarding the physiological state of an organism. The aim of this work was to evaluate a protocol for high-throughput NMR-based analysis of polar and non-polar metabolites from a small quantity of liver tissue. We extracted the tissue with a methanol/chloroform/water mixture and isolated the polar metabolites from the methanol/water layer and the non-polar metabolites from the chloroform layer. Following drying, we re-solubilized the fractions for analysis with a 600 MHz NMR spectrometer equipped with a 1.7 mm cryogenic probe. In order to evaluate the feasibility of this protocol for metabolomics studies, we analyzed the metabolic profile of livers from house sparrow ( Passer domesticus ) nestlings raised on two different diets: livers from 10 nestlings raised on a high protein diet (HP) for 4 d and livers from 12 nestlings raised on the HP diet for 3 d and then switched to a high carbohydrate diet (HC) for 1 d. The protocol enabled the detection of 52 polar and nine non-polar metabolites in ¹H NMR spectra of the extracts. We analyzed the lipophilic metabolites by one-way ANOVA to assess statistically significant concentration differences between the two groups. The results of our studies demonstrate that the protocol described here can be exploited for high-throughput screening of small quantities of liver tissue (approx. 100 mg wet mass) obtainable from small animals.

  7. Influence of Freezing and Storage Procedure on Human Urine Samples in NMR-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Burkhard Luy

    2013-04-01

    Full Text Available It is consensus in the metabolomics community that standardized protocols should be followed for sample handling, storage and analysis, as it is of utmost importance to maintain constant measurement conditions to identify subtle biological differences. The aim of this work, therefore, was to systematically investigate the influence of freezing procedures and storage temperatures and their effect on NMR spectra as a potentially disturbing aspect for NMR-based metabolomics studies. Urine samples were collected from two healthy volunteers, centrifuged and divided into aliquots. Urine aliquots were frozen either at −20 °C, on dry ice, at −80 °C or in liquid nitrogen and then stored at −20 °C, −80 °C or in liquid nitrogen vapor phase for 1–5 weeks before NMR analysis. Results show spectral changes depending on the freezing procedure, with samples frozen on dry ice showing the largest deviations. The effect was found to be based on pH differences, which were caused by variations in CO2 concentrations introduced by the freezing procedure. Thus, we recommend that urine samples should be frozen at −20 °C and transferred to lower storage temperatures within one week and that freezing procedures should be part of the publication protocol.

  8. Metabonomic Study on the Antidepressant-Like Effects of Banxia Houpu Decoction and Its Action Mechanism

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    Zhanqiang Ma

    2013-01-01

    Full Text Available The aim of this study was to establish an experimental model for metabonomic profiles of the rat’s brain and then to investigate the antidepressant effect of Banxia Houpu decoction (BHD and its possible mechanisms. Behavioral research and metabonomics method based on UPLC-MS were used to assess the efficacy of different fractions of BHD on chronic unpredictable mild stress (CUMS model of depression. There was a significant difference between the BHD group and the model group. Eight endogenous metabolites, which are contributing to the separation of the model group and control group, were detected, while BHD group regulated the perturbed metabolites showing that there is a tendency of recovery compared to control group. Therefore, we think that those potential metabolite biomarkers have some relationship with BHD’s antidepression effect. This work appraised the antidepressant effect of Banxia Houpu decoction as well as revealing a metabonomics method, a valuable parameter in the TCM research.

  9. Differences of Excess and Deficiency Zheng in Patients with Chronic Hepatitis B by Urinary Metabonomics

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    Shujun Sun

    2013-01-01

    Full Text Available Traditional Chinese medicine (TCM physicians stratify patients with the same disease into different subtypes in order to guide the appropriate treatment, which is called Zheng (TCM syndrome classification. Excess and deficiency ZHENG is a couple of basic ZHENGs of maladjusted body nature, reflecting the struggling state of human body and pathogenic factor and is important and prevalently exists in the ZHENG classification of many diseases. The present work using chronic hepatitis B (CHB as an entry point explored the substance connotation of excess and deficiency ZHENG with the metabonomic technology based on gas chromatography-mass spectrometry (GC-MS. The different substantial basis of two ZHENGs suggested that CHB patients could be categorized into two groups with diverse pathogenesis. The differential metabolites and disturbed pathways compared to not-obvious ZHENG characters patients (without ZHENG group/WZ were selected in both of the two ZHENGs. The ROC analysis demonstrated that five metabolites had a greater potential to be the clinic biomarkers of EZ or DZ. And excess ZHENG revealed a higher level of immune function than deficiency ZHENG. We are eager to transform the concept of traditional excess and deficiency ZHENGs to modern therapeutic approaches, with the prospect to help to promote personalized medicine.

  10. Plasma metabonomics study of first-Episode schizophrenia treated with olanzapine in female patients.

    Science.gov (United States)

    Qiao, Ying; Zhang, Lei; He, Shen; Wen, Hui; Yu, Yi-Min; Cao, Chun-Hua; Li, Hua-Fang

    2016-03-23

    Schizophrenia is a persistent chronic mental illness with an unknown pathogenic mechanism; no empirical laboratory-based tests are available to support the diagnosis of schizophrenia or to identify biomarkers correlated with the therapeutic effect of olanzapine. For this study, 15 female first-episode, drug-naïve patients with schizophrenia and 15 healthy female volunteers were recruited. Tests for blood glucose and lipids were conducted at baseline and after 4 weeks of treatment with olanzapine. UPLC-MS based metabonomic analysis was performed on both case and control groups to identify biomarkers of schizophrenia at baseline and to explore which biomarkers correlated with the therapeutic effect of olanzapine after a 4-week treatment. Compared with the control group, the case group showed significant changes in plasma metabolites. Thirteen distinct metabolites were identified. Among all the therapeutically effective cases, levels of these metabolites appeared to shift towards the normal trend; 8 of the identified 13 metabolites changed dramatically. The metabolites that we found are potential biomarkers for the diagnosis and treatment of schizophrenia. Copyright © 2016. Published by Elsevier Ireland Ltd.

  11. Metabolic Profiling and Classification of Propolis Samples from Southern Brazil: An NMR-Based Platform Coupled with Machine Learning.

    Science.gov (United States)

    Maraschin, Marcelo; Somensi-Zeggio, Amélia; Oliveira, Simone K; Kuhnen, Shirley; Tomazzoli, Maíra M; Raguzzoni, Josiane C; Zeri, Ana C M; Carreira, Rafael; Correia, Sara; Costa, Christopher; Rocha, Miguel

    2016-01-22

    The chemical composition of propolis is affected by environmental factors and harvest season, making it difficult to standardize its extracts for medicinal usage. By detecting a typical chemical profile associated with propolis from a specific production region or season, certain types of propolis may be used to obtain a specific pharmacological activity. In this study, propolis from three agroecological regions (plain, plateau, and highlands) from southern Brazil, collected over the four seasons of 2010, were investigated through a novel NMR-based metabolomics data analysis workflow. Chemometrics and machine learning algorithms (PLS-DA and RF), including methods to estimate variable importance in classification, were used in this study. The machine learning and feature selection methods permitted construction of models for propolis sample classification with high accuracy (>75%, reaching ∼90% in the best case), better discriminating samples regarding their collection seasons comparatively to the harvest regions. PLS-DA and RF allowed the identification of biomarkers for sample discrimination, expanding the set of discriminating features and adding relevant information for the identification of the class-determining metabolites. The NMR-based metabolomics analytical platform, coupled to bioinformatic tools, allowed characterization and classification of Brazilian propolis samples regarding the metabolite signature of important compounds, i.e., chemical fingerprint, harvest seasons, and production regions.

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

    Science.gov (United States)

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

    2016-09-01

    Pharmaceuticals and personal care products are a class of emerging contaminants that are present in wastewater effluents, surface water, and groundwater around the world. There is a need to determine rapid and reliable bioindicators of exposure and the toxic mode of action of these contaminants to aquatic organisms. (1)H nuclear magnetic resonance (NMR)-based metabolomics in combination with multivariate statistical analysis was used to determine the metabolic profile of Daphnia magna after exposure to a range of sub-lethal concentrations of triclosan (6.25-100μg/L), carbamazepine (1.75-14mg/L) and ibuprofen (1.75-14mg/L) for 48h. Sub-lethal triclosan exposure suggested a general oxidative stress condition and the branched-chain amino acids, glutamine, glutamate, and methionine emerged as potential bioindicators. The aromatic amino acids, serine, glycine and alanine are potential bioindicators for sub-lethal carbamazepine exposure that may have altered energy metabolism. The potential bioindicators for sub-lethal ibuprofen exposure are serine, methionine, lysine, arginine and leucine, which showed a concentration-dependent response. The differences in the metabolic changes were related to the dissimilar modes of toxicity of triclosan, carbamazepine and ibuprofen. (1)H NMR-based metabolomics gave an improved understanding of how these emerging contaminants impact the keystone species D. magna. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Biological responses to perfluorododecanoic acid exposure in rat kidneys as determined by integrated proteomic and metabonomic studies.

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    Hongxia Zhang

    Full Text Available BACKGROUND: Perfluorododecanoic acid (PFDoA is a perfluorinated carboxylic chemical (PFC that has broad applications and distribution in the environment. While many studies have focused on hepatotoxicity, immunotoxicity, and reproductive toxicity of PFCAs, few have investigated renal toxicity. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used comparative proteomic and metabonomic technologies to provide a global perspective on renal response to PFDoA. Male rats were exposed to 0, 0.05, 0.2, and 0.5 mg/kg/day of PFDoA for 110 days. After 2-D DIGE and MALDI TOF/TOF analysis, 79 differentially expressed proteins between the control and the PFDoA treated rats (0.2 and 0.5 mg-dosed groups were successfully identified. These proteins were mainly involved in amino acid metabolism, the tricarboxylic acid cycle, gluconeogenesis, glycolysis, electron transport, and stress response. Nuclear magnetic resonance-based metabonomic analysis showed an increase in pyruvate, lactate, acetate, choline, and a variety of amino acids in the highest dose group. Furthermore, the profiles of free amino acids in the PFDoA treated groups were investigated quantitatively by high-coverage quantitative iTRAQ-LC MS/MS, which showed levels of sarcosine, asparagine, histidine, 1-methylhistidine, Ile, Leu, Val, Trp, Tyr, Phe, Cys, and Met increased markedly in the 0.5 mg dosed group, while homocitrulline, α-aminoadipic acid, β-alanine, and cystathionine decreased. CONCLUSION/SIGNIFICANCE: These observations provide evidence that disorders in glucose and amino acid metabolism may contribute to PFDoA nephrotoxicity. Additionally, α(2u globulin may play an important role in protecting the kidneys from PFDoA toxicity.

  14. Lessons from Metabonomics on the Neurobiology of Stroke.

    Science.gov (United States)

    Qureshi, Mahim I; Vorkas, Panagiotis A; Coupland, Alexander P; Jenkins, I Harri; Holmes, Elaine; Davies, Alun H

    2016-10-01

    The application of metabonomic science to interrogate stroke permits the study of metabolite entities, small enough to cross the blood-brain barrier, that provide insight into neuronal dysfunction, and may serve as reservoirs of biomarker discovery. This systematic review examines the applicability of metabolic profiling in ischemic stroke research. Six human studies utilizing metabolic profiling to analyze biofluids from ischemic stroke patients have been included, employing 1 H-NMR and/or mass spectrometry to analyze plasma, serum, and/or urine in a targeted or untargeted fashion. Three are diagnostic studies, and one investigates prognostic biomarkers of stroke recurrence following transient ischemic attack. Two studies focus on metabolic distinguishers of depression or cognitive impairment following stroke. Identified biomarkers from blood and urine predominantly relate to homocysteine and folate, branched chain amino acid, and lipid metabolism. Statistical models are well fitted and reproducible, with excellent validation outcomes, demonstrating the feasibility of metabolic profiling to study a complex disorder with multicausal pathology, such as stroke.

  15. 1H NMR- based metabolomics approaches as non- invasive tools for diagnosis of endometriosis

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    Negar Ghazi

    2016-01-01

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

  16. GC-MS-Based Metabonomic Profiling Displayed Differing Effects of Borna Disease Virus Natural Strain Hu-H1 and Laboratory Strain V Infection in Rat Cortical Neurons.

    Science.gov (United States)

    Liu, Siwen; Bode, Liv; Zhang, Lujun; He, Peng; Huang, Rongzhong; Sun, Lin; Chen, Shigang; Zhang, Hong; Guo, Yujie; Zhou, Jingjing; Fu, Yuying; Zhu, Dan; Xie, Peng

    2015-08-17

    Borna disease virus (BDV) persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON) cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC-MS) metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12), Strain V-infected cells (n = 12), and CON cells (n = 11). Partial least squares discriminant analysis (PLS-DA) was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON), 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON), and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V). Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.

  17. Yuanhuapine-induced intestinal and hepatotoxicity were correlated with disturbance of amino acids, lipids, carbohydrate metabolism and gut microflora function: A rat urine metabonomic study.

    Science.gov (United States)

    Chen, Yanyan; Duan, Jin-Ao; Guo, Jianming; Shang, Erxin; Tang, Yuping; Qian, Yefei; Tao, Weiwei; Liu, Pei

    2016-07-15

    This research was designed to study metabonomic characteristics of the toxicity induced by yuanhuapine, a major bioactive diterpenoid in a well-known traditional Chinese medicine-Genkwa Flos. General observation, blood biochemistry and histopathological examination were used to reflect yuanhuapine-induced toxicity. Urine samples from rats in control and yuanhuapine treated rats were analyzed by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Pattern recognition methods including principal components analysis (PCA), partial least-squared discriminant analysis (PLS-DA), orthogonal partial least-squared discriminant analysis (OPLS-DA) and computational system analysis were integrated to obtain comprehensive metabonomic profiling and pathways of the biological data sets. The results suggested that yuanhuapine could induce intestinal and liver damage. And 14 endogenous metabolites as biomarkers related to the amino acids metabolism, lipids metabolism, carbohydrate metabolism and gut microflora were significantly changed in the urine of yuanhuapine treated rats, which were firstly constructed the metabolomic feature profiling and metabolite interaction network of yuanhuapine-induced injury using pattern recognition methods and Ingenuity Pathway Analysis (IPA) approach. The present study showed that yuanhuapine-induced intestinal and hepatic toxicity were correlated with disturbance of amino acids metabolism, lipids metabolism, carbohydrate metabolism and gut microflora. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. NMR-based metabolomics of mammalian cell and tissue cultures

    International Nuclear Information System (INIS)

    Aranibar, Nelly; Borys, Michael; Mackin, Nancy A.; Ly, Van; Abu-Absi, Nicholas; Abu-Absi, Susan; Niemitz, Matthias; Schilling, Bernhard; Li, Zheng Jian; Brock, Barry; Russell, Reb J.; Tymiak, Adrienne; Reily, Michael D.

    2011-01-01

    NMR spectroscopy was used to evaluate growth media and the cellular metabolome in two systems of interest to biomedical research. The first of these was a Chinese hamster ovary cell line engineered to express a recombinant protein. Here, NMR spectroscopy and a quantum mechanical total line shape analysis were utilized to quantify 30 metabolites such as amino acids, Krebs cycle intermediates, activated sugars, cofactors, and others in both media and cell extracts. The impact of bioreactor scale and addition of anti-apoptotic agents to the media on the extracellular and intracellular metabolome indicated changes in metabolic pathways of energy utilization. These results shed light into culture parameters that can be manipulated to optimize growth and protein production. Second, metabolomic analysis was performed on the superfusion media in a common model used for drug metabolism and toxicology studies, in vitro liver slices. In this study, it is demonstrated that two of the 48 standard media components, choline and histidine are depleted at a faster rate than many other nutrients. Augmenting the starting media with extra choline and histidine improves the long-term liver slice viability as measured by higher tissues levels of lactate dehydrogenase (LDH), glutathione and ATP, as well as lower LDH levels in the media at time points out to 94 h after initiation of incubation. In both models, media components and cellular metabolites are measured over time and correlated with currently accepted endpoint measures.

  19. Automatic NMR-based identification of chemical reaction types in mixtures of co-occurring reactions.

    Directory of Open Access Journals (Sweden)

    Diogo A R S Latino

    Full Text Available The combination of chemoinformatics approaches with NMR techniques and the increasing availability of data allow the resolution of problems far beyond the original application of NMR in structure elucidation/verification. The diversity of applications can range from process monitoring, metabolic profiling, authentication of products, to quality control. An application related to the automatic analysis of complex mixtures concerns mixtures of chemical reactions. We encoded mixtures of chemical reactions with the difference between the (1H NMR spectra of the products and the reactants. All the signals arising from all the reactants of the co-occurring reactions were taken together (a simulated spectrum of the mixture of reactants and the same was done for products. The difference spectrum is taken as the representation of the mixture of chemical reactions. A data set of 181 chemical reactions was used, each reaction manually assigned to one of 6 types. From this dataset, we simulated mixtures where two reactions of different types would occur simultaneously. Automatic learning methods were trained to classify the reactions occurring in a mixture from the (1H NMR-based descriptor of the mixture. Unsupervised learning methods (self-organizing maps produced a reasonable clustering of the mixtures by reaction type, and allowed the correct classification of 80% and 63% of the mixtures in two independent test sets of different similarity to the training set. With random forests (RF, the percentage of correct classifications was increased to 99% and 80% for the same test sets. The RF probability associated to the predictions yielded a robust indication of their reliability. This study demonstrates the possibility of applying machine learning methods to automatically identify types of co-occurring chemical reactions from NMR data. Using no explicit structural information about the reactions participants, reaction elucidation is performed without structure

  20. Automatic NMR-based identification of chemical reaction types in mixtures of co-occurring reactions.

    Science.gov (United States)

    Latino, Diogo A R S; Aires-de-Sousa, João

    2014-01-01

    The combination of chemoinformatics approaches with NMR techniques and the increasing availability of data allow the resolution of problems far beyond the original application of NMR in structure elucidation/verification. The diversity of applications can range from process monitoring, metabolic profiling, authentication of products, to quality control. An application related to the automatic analysis of complex mixtures concerns mixtures of chemical reactions. We encoded mixtures of chemical reactions with the difference between the (1)H NMR spectra of the products and the reactants. All the signals arising from all the reactants of the co-occurring reactions were taken together (a simulated spectrum of the mixture of reactants) and the same was done for products. The difference spectrum is taken as the representation of the mixture of chemical reactions. A data set of 181 chemical reactions was used, each reaction manually assigned to one of 6 types. From this dataset, we simulated mixtures where two reactions of different types would occur simultaneously. Automatic learning methods were trained to classify the reactions occurring in a mixture from the (1)H NMR-based descriptor of the mixture. Unsupervised learning methods (self-organizing maps) produced a reasonable clustering of the mixtures by reaction type, and allowed the correct classification of 80% and 63% of the mixtures in two independent test sets of different similarity to the training set. With random forests (RF), the percentage of correct classifications was increased to 99% and 80% for the same test sets. The RF probability associated to the predictions yielded a robust indication of their reliability. This study demonstrates the possibility of applying machine learning methods to automatically identify types of co-occurring chemical reactions from NMR data. Using no explicit structural information about the reactions participants, reaction elucidation is performed without structure elucidation of

  1. Data-handling strategies for metabonomic studies: example of the UHPLC-ESI/ToF urinary signature of tetrahydrocannabinol in humans.

    Science.gov (United States)

    Kiss, Agneta; Bordes, Claire; Buisson, Corinne; Lasne, Francoise; Lanteri, Pierre; Cren-Olivé, Cécile

    2014-02-01

    Metabonomics has become a very valuable tool and many research fields rely on results coming out from this combination of analytical techniques, chemometric strategies, and biological interpretation. Moreover, the matrices are more and more complex and the implications of the results are often of major importance. In this context, the need for pertinent validation strategies comes naturally. The choice of the appropriate chemometric method remains nevertheless a difficult task due to particularities such as: the number of measured variables, the complexity of the matrix and the purposes of the study. Consequently, this paper presents a detailed metabonomic study on human urine with a special emphasis on the importance of assessing the data's quality. It also describes, step by step, the statistical tools currently used and offers a critical view on some of their limits. In this work, 29 urine samples among which 15 samples obtained from tetrahydrocannabinol (delta-9-tetrahydrocannabinol)-consuming athletes, 5 samples provided by volunteers, and 9 samples obtained from athletes were submitted to untargeted analysis by means of ultra high-pressure liquid chromatography-electrospray ionization-time-of-flight mass spectrometry. Next, the quality of the obtained data was assessed and the results were compared to those found in databases. Then, unsupervised (principal component analysis (PCA)) and supervised (ANOVA/PCA, partial least-square-discriminant analysis (PLS-DA), orthogonal PLS-DA) univariate and multivariate statistical methods were applied.

  2. A metabonomic approach for mechanistic exploration of pre-clinical toxicology.

    Science.gov (United States)

    Coen, Muireann

    2010-12-30

    Metabonomics involves the application of advanced analytical tools to profile the diverse metabolic complement of a given biofluid or tissue. Subsequent statistical modelling of the complex multivariate spectral profiles enables discrimination between phenotypes of interest and identifies panels of discriminatory metabolites that represent candidate biomarkers. This review article presents an overview of recent developments in the field of metabonomics with a focus on application to pre-clinical toxicology studies. Recent research investigations carried out as part of the international COMET 2 consortium project on the hepatotoxic action of the aminosugar, galactosamine (galN) are presented. The application of advanced, high-field NMR spectroscopy is demonstrated, together with complementary application of a targeted mass spectrometry platform coupled with ultra-performance liquid chromatography. Much novel mechanistic information has been gleaned on both the mechanism of galN hepatotoxicity in multiple biofluids and tissues, and on the protection afforded by co-administration of glycine and uridine. The simultaneous identification of both the metabolic fate of galN and its associated endogenous consequences in spectral profiles is demonstrated. Furthermore, metabonomic assessment of inter-animal variability in response to galN presents enhanced mechanistic insight on variable response phentoypes and is relevant to understanding wider aspects of individual variability in drug response. This exemplar highlights the analytical and statistical tools commonly applied in metabonomic studies and notably, the approach is applicable to the study of any toxin/drug or intervention of interest. The metabonomic approach holds considerable promise and potential to significantly advance our understanding of the mechanistic bases for adverse drug reactions. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-15

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

  4. NMR-based urinalysis for rapid diagnosis of β-ureidopropionase deficiency in a patient with Dravet syndrome.

    Science.gov (United States)

    Lam, Ching-Wan; Law, Chun-Yiu; Leung, Ka-Fei; Lai, Chi-Kong; Pak-lam Chen, Sammy; Chan, Bosco; Chan, Kwok-Yin; Yuen, Yuet-ping; Mak, Chloe Miu; Yan-wo Chan, Albert

    2015-02-02

    Beta-ureidopropionase deficiency is a rare inborn error of metabolism (IEM) affecting pyrimidine metabolism. To-date, about 30 genetically confirmed cases had been reported. The clinical phenotypes of this condition are variable; some patients were asymptomatic while some may present with developmental delay or autistic features. In severe cases, patients may present with profound neurological deficit including hypotonia, seizures and mental retardation. Using NMR-based urinalysis, this condition can be rapidly diagnosed within 15 min. An 11-month-old Chinese boy had dual molecular diagnoses, β-ureidopropionase deficiency and Dravet syndrome. He presented with intractable and recurrent convulsions, global developmental delay and microcephaly. Urine organic acid analysis using GC-MS and NMR-based urinalysis showed excessive amount of β-ureidopropionic acid and β-ureidoisobutyric acid, the two disease-specific markers for β-ureidopropionase deficiency. Genetic analysis confirmed homozygous known disease-causing mutation UPB1 NM_016327.2: c.977G>A; NP_057411.1:p.R326Q. In addition, genetic analysis for Dravet syndrome showed the presence of heterozygous disease-causing mutation SCN1A NM_001165963.1:c.4494delC; NP_001159435.1:p.F1499Lfs*2. The differentiation between Dravet syndrome and β-ureidopropionase deficiency is clinically challenging since both conditions share overlapping clinical features. The detection of urine β-ureidoisobutyric and β-ureidopropionic acids using NMR or GC-MS is helpful in laboratory diagnosis of β-ureidopropionase deficiency. The disease-causing mutation, c.977G>A of β-ureidopropionase deficiency, is highly prevalent in Chinese population (allele frequency=1.7%); β-ureidopropionase deficiency screening test should be performed for any patients with unexplained neurological deficit, developmental delay or autism. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2014-02-26

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

  6. Application of NMR-based metabolomics for environmental assessment in the Great Lakes using zebra mussel (Dreissena polymorpha).

    Science.gov (United States)

    Watanabe, Miki; Meyer, Kathryn A; Jackson, Tyler M; Schock, Tracey B; Johnson, W Edward; Bearden, Daniel W

    Zebra mussel, Dreissena polymorpha , in the Great Lakes is being monitored as a bio-indicator organism for environmental health effects by the National Oceanic and Atmospheric Administration's Mussel Watch program. In order to monitor the environmental effects of industrial pollution on the ecosystem, invasive zebra mussels were collected from four stations-three inner harbor sites (LMMB4, LMMB1, and LMMB) in Milwaukee Estuary, and one reference site (LMMB5) in Lake Michigan, Wisconsin. Nuclear magnetic resonance (NMR)-based metabolomics was used to evaluate the metabolic profiles of the mussels from these four sites. The objective was to observe whether there were differences in metabolite profiles between impacted sites and the reference site; and if there were metabolic profile differences among the impacted sites. Principal component analyses indicated there was no significant difference between two impacted sites: north Milwaukee harbor (LMMB and LMMB4) and the LMMB5 reference site. However, significant metabolic differences were observed between the impacted site on the south Milwaukee harbor (LMMB1) and the LMMB5 reference site, a finding that correlates with preliminary sediment toxicity results. A total of 26 altered metabolites (including two unidentified peaks) were successfully identified in a comparison of zebra mussels from the LMMB1 site and LMMB5 reference site. The application of both uni- and multivariate analysis not only confirmed the variability of altered metabolites but also ensured that these metabolites were identified via unbiased analysis. This study has demonstrated the feasibility of the NMR-based metabolomics approach to assess whole-body metabolomics of zebra mussels to study the physiological impact of toxicant exposure at field sites.

  7. Metabonomics Combined with UPLC-MS Chemical Profile for Discovery of Antidepressant Ingredients of a Traditional Chinese Medicines Formula, Chaihu-Shu-Gan-San

    Directory of Open Access Journals (Sweden)

    Hongmei Jia

    2013-01-01

    Full Text Available This study proposed a new strategy for uncovering the active chemical constituents of a traditional Chinese medicines (TCMs formula, Chaihu-Shu-Gan-San (CSGS. Metabonomics and chemical profile were integrated in combination with the multivariate statistical analysis (MVA to discover the chemical constituents which contribute to the antidepressant effect of CSGS. Based upon the difference between CSGS and QZ (CSGS without Zhi-Qiao extracts in the chemical profiles and the regulations of metabolic disturbances induced by CUMS, synephrine, naringin, hesperidin, and neohesperidin were recognized as the active constituents of CSGS from Zhi-qiao responsible for those missing regulations of CSGS when Zhi-Qiao was subtracted from the whole formula. They participated in the regulations of the deviated metabolites 2–4, 10–14, and 22–25, involved in metabolic pathways of ketone bodies synthesis, phenylalanine, tyrosine and tryptophan biosynthesis, valine, aspartate, glutamate metabolism, and glycolysis/gluconeogenesis. Furthermore, the assay of MAO-A activity confirmed the potential antidepressant effect of naringin and its active sites on the MAO-A was inferred by molecular docking study. The integration of metabonomics and chemical profile was proved to be a useful strategy for uncovering what the active chemical constituents in TCM formula are and how they make contributions for the efficacy of the formula.

  8. Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

    Science.gov (United States)

    Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

    2018-02-14

    Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-01-15

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

  10. 1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats

    Directory of Open Access Journals (Sweden)

    Atul Rawat

    2016-01-01

    Full Text Available Introduction: Erythromycin (ERY is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Objective: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. Experimental: Fourteen male rats were randomly divided into two groups (n = 7 in each group: control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. Results: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a decreased TCA cycle activity and enhanced fatty acid oxidation, (b dysfunction of lipid and amino acid metabolism and (c oxidative stress. Conclusion and Recommendations: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new

  11. Study of a novel indolin-2-ketone compound Z24 induced hepatotoxicity by NMR-spectroscopy-based metabonomics of rat urine, blood plasma, and liver extracts

    International Nuclear Information System (INIS)

    Wang Quanjun; Jiang Ying; Wu Chunqi; Zhao Jianyu; Yu Shouzhong; Yuan Benli; Yan Xianzhong; Liao Mingyang

    2006-01-01

    Antiangiogenic compound has been believed to be an ideal drug in the current cancer biological therapy, but the angiogenesis inhibitors suffer setback for unknown toxicity now. A novel synthetic indolin-s-ketone small molecular compound, 3Z-3-[( 1 H-pyrrol-2-yl)-methylidene]-1-(1-piperidinylmethyl)-1,3-2H-indol-2-one (Z24) can inhibit angiogenesis in new blood vessels. The hepatotoxicity effects of Z24 oral administration (dosed at 60, 130 and 200 mg/kg) have been investigated in female Wistar rats by using metabonomic analysis of 1 H NMR spectra of urine, plasma and liver extracts, as well as by clinical chemistry analysis, liver histopathology and electron micrographs examination. The 1 H NMR spectra of the biofluids were analyzed visually and via pattern recognition by using principal component analysis. The metabonomic trajectory analysis on the time-related hepatotoxicity of Z24 was carried out based on the 1 H NMR spectra of urine samples, which were collected daily predose and postdose over an 8-day period. Urinary excretion of citrate, lactate, 2-oxo-glutarate and succinate increased following Z24 dosing. Increased plasma levels of lactate, TMAO and lipid were observed, with concomitant decrease in the level of glucose and phosphatidylcholine. Metabolic profiling on aqueous soluble extracts of liver tissues with the high dose level of Z24 showed an increase in lactate and glutamine, together with a decrease in glucose, glycogen and choline. On the other hand, studies on lipid soluble extracts of liver tissues with the high dose level of Z24 showed increased level in lipid triglycerides and decreased level in unsaturated fatty acids and phosphatidylcholine. Moreover, the most notable effect of Z24 on the metabolism was the reduction in the urinary levels of creatinine and TMAO and the increase in acetate, citrate, succinate and 2-oxo-glutamate with time dependence. The results indicate that in rats Z24 inhibits mitochondrial function through altering the

  12. Windowed direct exponential curve resolution quantification of nuclear magnetic resonance spectroscopy with applications to amniotic fluid metabonomics

    International Nuclear Information System (INIS)

    Botros, L.L.

    2007-01-01

    This thesis presents a quantitative protocol of proton nuclear magnetic resonance ( 1 H NMR) that allows the determination of human amniotic fluid metabolite concentrations, which are then used in a metabonomic study to establish patient health during gestation. 1 H NMR free inductive decays (FIDs) of 258 human amniotic fluid samples from a 500MHz spectrometer are acquired. Quantitative analyses methods in both the frequency- and time-domain are carried out and compared. Frequency-domain analysis is accomplished by integration of the metabolite peaks before and after the inclusion of a known standard addition of alanine. Time-domain analysis is accomplished by the direct exponential curve resolution algorithm (DECRA). Both techniques are assessed by applications to calibration biological solutions and a simulated data set. The DECRA method proves to be a more accurate and precise route for quantitative analysis, and is included in the developed protocol. Well-defined peaks of various components are visible in the frequency-domain 1 H NMR spectra, including lactate, alanine, acetate, citrate, choline, glycine, and glucose. All are quantified with the proposed protocol. Statistical t-test and notched box and whisker plots are used to compare means of metabolite concentrations for diabetic and normal patients. Glucose, glycine, and choline are all found to correlate with gestational diabetes mellitus early in gestation. With further development, time-domain quantitative 1 H NMR has potential to become a robust diagnostic tool for gestational health. (author)

  13. Windowed direct exponential curve resolution quantification of nuclear magnetic resonance spectroscopy with applications to amniotic fluid metabonomics

    Energy Technology Data Exchange (ETDEWEB)

    Botros, L.L

    2007-07-01

    This thesis presents a quantitative protocol of proton nuclear magnetic resonance ({sup 1}H NMR) that allows the determination of human amniotic fluid metabolite concentrations, which are then used in a metabonomic study to establish patient health during gestation. {sup 1}H NMR free inductive decays (FIDs) of 258 human amniotic fluid samples from a 500MHz spectrometer are acquired. Quantitative analyses methods in both the frequency- and time-domain are carried out and compared. Frequency-domain analysis is accomplished by integration of the metabolite peaks before and after the inclusion of a known standard addition of alanine. Time-domain analysis is accomplished by the direct exponential curve resolution algorithm (DECRA). Both techniques are assessed by applications to calibration biological solutions and a simulated data set. The DECRA method proves to be a more accurate and precise route for quantitative analysis, and is included in the developed protocol. Well-defined peaks of various components are visible in the frequency-domain {sup 1}H NMR spectra, including lactate, alanine, acetate, citrate, choline, glycine, and glucose. All are quantified with the proposed protocol. Statistical t-test and notched box and whisker plots are used to compare means of metabolite concentrations for diabetic and normal patients. Glucose, glycine, and choline are all found to correlate with gestational diabetes mellitus early in gestation. With further development, time-domain quantitative {sup 1}H NMR has potential to become a robust diagnostic tool for gestational health. (author)

  14. Metabonomics study on the hepatoprotective effect of polysaccharides from different preparations of Angelica sinensis.

    Science.gov (United States)

    Hua, Yongli; Xue, Wenxin; Zhang, Man; Wei, Yanming; Ji, Peng

    2014-02-12

    Angelica sinensis (AS) has been used for thousands of years in Traditional Chinese Medicine (TCM). Processed products of AS mainly include charred Angelica, parching Angelica with oil, parching Angelica with wine, and parching Angelica with soil, which have been widely used in TCM prescriptions. Polysaccharides are important chemical substances of AS. These compounds effectively treat liver diseases, shows hepatoprotectivity, and contributes directly to the therapeutic effect of AS. However, the precise molecular mechanism of the effects of the different AS products polysaccharide has not been comprehensively explored. The present investigation was designed to assess the effects and possible mechanisms of polysaccharide in the different AS products against carbon tetrachloride-induced liver injury. Liver injury was induced by intraperitoneal injection with Carbon tetrachloride (CCl4) in the mice. Gas chromatography-mass spectrometry (GC-MS) combined with pattern recognition approaches, namely, principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were used to determine differentiating metabolites in plasma and liver tissue. PCA and PLS-DA score plots of the liver injury group clustered separately from that of the control, while groups treated with polysaccharides from charred AS (ASTP), parching AS with soil (ASTUP), parching AS with wine (ASJP), parching AS with Sesame Oil (ASYP) clustered closely with the control. This result indicates that the metabolic profiles of the ASTP, ASTUP, ASJP, and ASYP groups are almost similar to those of the control. Potential metabolite biomarkers (six in the liver homogenates and seven in the plasma) were identified. These biomarkers include citric acid, succinic acid,glycine, palmitelaidic acid, arachidonic acid, fumaric acid, malic acid, valine, ananine, and hexadecanoic acid. Functional pathway analysis revealed that alterations in these metabolites are associated with lipid, amino acid

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

    Directory of Open Access Journals (Sweden)

    Monica Scognamiglio

    2015-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  17. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    International Nuclear Information System (INIS)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-01-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by 1 H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome

  18. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

    Energy Technology Data Exchange (ETDEWEB)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang [Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Zhang, Yuanzhen [Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Center for Reproductive Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen 361005 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China)

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal

  19. 1H NMR-based metabolite profiling of plasma in a rat model of chronic kidney disease.

    Directory of Open Access Journals (Sweden)

    Ju-Ae Kim

    Full Text Available Chronic kidney disease (CKD is characterized by the gradual loss of the kidney function to excrete wastes and fluids from the blood. (1H NMR-based metabolomics was exploited to investigate the altered metabolic pattern in rats with CKD induced by surgical reduction of the renal mass (i.e., 5/6 nephrectomy (5/6 Nx, particularly for identifying specific metabolic biomarkers associated with early of CKD. Plasma metabolite profiling was performed in CKD rats (at 4- or 8-weeks after 5/6 Nx compared to sham-operated rats. Principle components analysis (PCA, partial least squares-discriminant analysis (PLS-DA and orthogonal partial least squares-discriminant analysis (OPLS-DA score plots showed a significant separation between the groups. The resulting metabolic profiles demonstrated significantly increased plasma levels of organic anions, including citrate, β-hydroxybutyrate, lactate, acetate, acetoacetate, and formate in CKD. Moreover, levels of alanine, glutamine, and glutamate were significantly higher. These changes were likely to be associated with complicated metabolic acidosis in CKD for counteracting systemic metabolic acidosis or increased protein catabolism from muscle. In contrast, levels of VLDL/LDL (CH2n and N-acetylglycoproteins were decreased. Taken together, the observed changes of plasma metabolite profiles in CKD rats provide insights into the disturbed metabolism in early phase of CKD, in particular for the altered metabolism of acid-base and/or amino acids.

  20. Computer-aided design of fragment mixtures for NMR-based screening.

    Science.gov (United States)

    Arroyo, Xavier; Goldflam, Michael; Feliz, Miguel; Belda, Ignasi; Giralt, Ernest

    2013-01-01

    Fragment-based drug discovery is widely applied both in industrial and in academic screening programs. Several screening techniques rely on NMR to detect binding of a fragment to a target. NMR-based methods are among the most sensitive techniques and have the further advantage of yielding a low rate of false positives and negatives. However, NMR is intrinsically slower than other screening techniques; thus, to increase throughput in NMR-based screening, researchers often assay mixtures of fragments, rather than single fragments. Herein we present a fast and straightforward computer-aided method to design mixtures of fragments taken from a library that have minimized NMR signal overlap. This approach enables direct identification of one or several active fragments without the need for deconvolution. Our approach entails encoding of NMR spectra into a computer-readable format that we call a fingerprint, and minimizing the global signal overlap through a Monte Carlo algorithm. The scoring function used favors a homogenous distribution of the global signal overlap. The method does not require additional experimental work: the only data required are NMR spectra, which are generally recorded for each compound as a quality control measure before its insertion into the library.

  1. Acute psychoactive and toxic effects of D. metel on mice explained by 1H NMR based metabolomics approach.

    Science.gov (United States)

    Fu, Yonghong; Si, Zhihong; Li, Pumin; Li, Minghui; Zhao, He; Jiang, Lei; Xing, Yuexiao; Hong, Wei; Ruan, Lingyu; Wang, Jun-Song

    2017-08-01

    Datura metel L. (D. metel) is one well-known folk medical herb with wide application and also the most abused plants all over the world, mainly for spiritual or religious purpose, over-dosing of which often produces poisonous effects. In this study, mice were orally administered with the extract of D. metel once a day at doses for 10 mg/kg and 40 mg/kg for consecutive 4 days, 1 H NMR based metabolomics approach aided with histopathological inspection and biochemical assays were used for the first time to study the psychoactive and toxic effects of D. metel. Histopathological inspection revealed obvious hypertrophy of hepatocytes, karyolysis and karyorrhexis in livers as well as distinct nerve cell edema, chromatolysis and lower nuclear density in brains. The increased tissue level of methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD), decreased tissue level of glutathione (GSH) along with increased serum level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) suggested brain and liver injury induced by D. metel. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles supplemented with correlation network analysis revealed significant altered metabolites and related pathway that contributed to oxidative stress, energy metabolism disturbances, neurotransmitter imbalance and amino acid metabolism disorders.

  2. 1H NMR-Based Metabolic Profiling Reveals the Effects of Fluoxetine on Lipid and Amino Acid Metabolism in Astrocytes

    Directory of Open Access Journals (Sweden)

    Shunjie Bai

    2015-04-01

    Full Text Available Fluoxetine, a selective serotonin reuptake inhibitor (SSRI, is a prescribed and effective antidepressant and generally used for the treatment of depression. Previous studies have revealed that the antidepressant mechanism of fluoxetine was related to astrocytes. However, the therapeutic mechanism underlying its mode of action in astrocytes remains largely unclear. In this study, primary astrocytes were exposed to 10 µM fluoxetine; 24 h post-treatment, a high-resolution proton nuclear magnetic resonance (1H NMR-based metabolomic approach coupled with multivariate statistical analysis was used to characterize the metabolic variations of intracellular metabolites. The orthogonal partial least-squares discriminant analysis (OPLS-DA score plots of the spectra demonstrated that the fluoxetine-treated astrocytes were significantly distinguished from the untreated controls. In total, 17 differential metabolites were identified to discriminate the two groups. These key metabolites were mainly involved in lipids, lipid metabolism-related molecules and amino acids. This is the first study to indicate that fluoxetine may exert antidepressant action by regulating the astrocyte’s lipid and amino acid metabolism. These findings should aid our understanding of the biological mechanisms underlying fluoxetine therapy.

  3. Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project

    International Nuclear Information System (INIS)

    Lindon, John C.; Nicholson, Jeremy K.; Holmes, Elaine; Antti, Henrik; Bollard, Mary E.; Keun, Hector; Beckonert, Olaf; Ebbels, Timothy M.; Reily, Michael D.; Robertson, Donald; Stevens, Gregory J.; Luke, Peter; Breau, Alan P.; Cantor, Glenn H.; Bible, Roy H.; Niederhauser, Urs; Senn, Hans; Schlotterbeck, Goetz; Sidelmann, Ulla G.; Laursen, Steen M.; Tymiak, Adrienne; Car, Bruce D.; Lehman-McKeeman, Lois; Colet, Jean-Marie; Loukaci, Ali; Thomas, Craig

    2003-01-01

    The role that metabonomics has in the evaluation of xenobiotic toxicity studies is presented here together with a brief summary of published studies. To provide a comprehensive assessment of this approach, the Consortium for Metabonomic Toxicology (COMET) has been formed between six pharmaceutical companies and Imperial College of Science, Technology and Medicine (IC), London, UK. The objective of this group is to define methodologies and to apply metabonomic data generated using 1 H NMR spectroscopy of urine and blood serum for preclinical toxicological screening of candidate drugs. This is being achieved by generating databases of results for a wide range of model toxins which serve as the raw material for computer-based expert systems for toxicity prediction. The project progress on the generation of comprehensive metabonomic databases and multivariate statistical models for prediction of toxicity, initially for liver and kidney toxicity in the rat and mouse, is reported. Additionally, both the analytical and biological variation which might arise through the use of metabonomics has been evaluated. An evaluation of intersite NMR analytical reproducibility has revealed a high degree of robustness. Second, a detailed comparison has been made of the ability of the six companies to provide consistent urine and serum samples using a study of the toxicity of hydrazine at two doses in the male rat, this study showing a high degree of consistency between samples from the various companies in terms of spectral patterns and biochemical composition. Differences between samples from the various companies were small compared to the biochemical effects of the toxin. A metabonomic model has been constructed for urine from control rats, enabling identification of outlier samples and the metabolic reasons for the deviation. Building on this success, and with the completion of studies on approximately 80 model toxins, first expert systems for prediction of liver and kidney

  4. 1H NMR-based urinary metabolic profiling reveals changes in nicotinamide pathway intermediates due to postnatal stress model in rat.

    Science.gov (United States)

    Tomassini, Alberta; Vitalone, Annabella; Marini, Federico; Praticò, Giulia; Sciubba, Fabio; Bevilacqua, Marta; Delfini, Maurizio; Di Sotto, Antonella; Di Giacomo, Silvia; Mariani, Paola; Mammola, Caterina L; Gaudio, Eugenio; Miccheli, Alfredo; Mazzanti, Gabriela

    2014-12-05

    The maternal separation protocol in rodents is a widely recognized model of early life stress allowing acute and chronic physiological consequences to be studied. An (1)H NMR-based metabolomic approach was applied to urines to evaluate the systemic metabolic consequences of maternal separation stress in female rats after the beginning of weaning and 4 weeks later when the rats were reaching adulthood. Furthermore, because maternal separation is considered as a model mimicking the inflammatory bowel syndrome, the lactulose/mannitol test was used to evaluate the influence of postnatal maternal separation on gut permeability and mucosal barrier function by (1)H NMR spectroscopy analysis of urine. The results showed no statistical differences in gut permeability due to maternal separation. The application of ANOVA simultaneous component analysis allowed the contributions of physiological adaptations to the animal's development to be separated from the metabolic consequences due to postnatal stress. Systemic metabolic differences in the maternally separated pups were mainly due to the tryptophan/NAD pathway intermediate levels and to the methyladenosine level. Urinary NMR-based metabolic profiling allowed us to disentangle the metabolic adaptive response of the rats to postnatal stress during the animal's growth, highlighting the metabolic changes induced by weaning, gut closure, and maturity.

  5. NMR-based homology model for the solution structure of the C-terminal globular domain of EMILIN1

    Energy Technology Data Exchange (ETDEWEB)

    Verdone, Giuliana [Istituto Biochimico Italiano ' G. Lorenzini' (Italy); Corazza, Alessandra [Universita di Udine, Dipartimento di Scienze e Tecnologie Biomediche - MATI Centre of Excellence (Italy); Colebrooke, Simon A. [University of Oxford, Department of Biochemistry (United Kingdom); Cicero, Daniel; Eliseo, Tommaso [Universita di Tor Vergata, Dipartimento di Chimica (Italy); Boyd, Jonathan [University of Oxford, Department of Biochemistry (United Kingdom); Doliana, Roberto [Centro di Riferimento Oncologico di Aviano, Divisione di Oncologia Sperimentale 2 (Italy); Fogolari, Federico; Viglino, Paolo; Colombatti, Alfonso [Universita di Udine, Dipartimento di Scienze e Tecnologie Biomediche - MATI Centre of Excellence (Italy); Campbell, Iain D. [University of Oxford, Department of Biochemistry (United Kingdom); Esposito, Gennaro [Universita di Udine, Dipartimento di Scienze e Tecnologie Biomediche - MATI Centre of Excellence (Italy)], E-mail: gesposito@mail.dstb.uniud.it

    2009-02-15

    EMILIN1 is a glycoprotein of elastic tissues that has been recently linked to the pathogenesis of hypertension. The protein is formed by different independently folded structural domains whose role has been partially elucidated. In this paper the solution structure, inferred from NMR-based homology modelling of the C-terminal trimeric globular C1q domain (gC1q) of EMILIN1, is reported. The high molecular weight and the homotrimeric structure of the protein required the combined use of highly deuterated {sup 15}N, {sup 13}C-labelled samples and TROSY experiments. Starting from a homology model, the protein structure was refined using heteronuclear residual dipolar couplings, chemical shift patterns, NOEs and H-exchange data. Analysis of the gC1q domain structure of EMILIN1 shows that each protomer of the trimer adopts a nine-stranded {beta} sandwich folding topology which is related to the conformation observed for other proteins of the family. Distinguishing features, however, include a missing edge-strand and an unstructured 19-residue loop. Although the current data do not allow this loop to be precisely defined, the available evidence is consistent with a flexible segment that protrudes from each subunit of the globular trimeric assembly and plays a key role in inter-molecular interactions between the EMILIN1 gC1q homotrimer and its integrin receptor {alpha}4{beta}1.

  6. Standardizing the experimental conditions for using urine in NMR-based metabolomic studies with a particular focus on diagnostic studies: a review

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2014-11-21

    The metabolic composition of human biofluids can provide important diagnostic and prognostic information. Among the biofluids most commonly analyzed in metabolomic studies, urine appears to be particularly useful. It is abundant, readily available, easily stored and can be collected by simple, noninvasive techniques. Moreover, given its chemical complexity, urine is particularly rich in potential disease biomarkers. This makes it an ideal biofluid for detecting or monitoring disease processes. Among the metabolomic tools available for urine analysis, NMR spectroscopy has proven to be particularly well-suited, because the technique is highly reproducible and requires minimal sample handling. As it permits the identification and quantification of a wide range of compounds, independent of their chemical properties, NMR spectroscopy has been frequently used to detect or discover disease fingerprints and biomarkers in urine. Although protocols for NMR data acquisition and processing have been standardized, no consensus on protocols for urine sample selection, collection, storage and preparation in NMR-based metabolomic studies have been developed. This lack of consensus may be leading to spurious biomarkers being reported and may account for a general lack of reproducibility between laboratories. Here, we review a large number of published studies on NMR-based urine metabolic profiling with the aim of identifying key variables that may affect the results of metabolomics studies. From this survey, we identify a number of issues that require either standardization or careful accounting in experimental design and provide some recommendations for urine collection, sample preparation and data acquisition.

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

    Directory of Open Access Journals (Sweden)

    Jinping Jia

    2015-05-01

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

  8. (13)C NMR-based metabolomics for the classification of green coffee beans according to variety and origin.

    Science.gov (United States)

    Wei, Feifei; Furihata, Kazuo; Koda, Masanori; Hu, Fangyu; Kato, Rieko; Miyakawa, Takuya; Tanokura, Masaru

    2012-10-10

    (13)C NMR-based metabolomics was demonstrated as a useful tool for distinguishing the species and origins of green coffee bean samples of arabica and robusta from six different geographic regions. By the application of information on (13)C signal assignment, significantly different levels of 14 metabolites of green coffee beans were identified in the classifications, including sucrose, caffeine, chlorogenic acids, choline, amino acids, organic acids, and trigonelline, as captured by multivariate analytical models. These studies demonstrate that the species and geographical origin can be quickly discriminated by evaluating the major metabolites of green coffee beans quantitatively using (13)C NMR-based metabolite profiling.

  9. Metabonomic profiles delineate the effect of traditional Chinese medicine sini decoction on myocardial infarction in rats.

    Directory of Open Access Journals (Sweden)

    Guangguo Tan

    Full Text Available BACKGROUND: In spite of great advances in target-oriented Western medicine for treating myocardial infarction (MI, it is still a leading cause of death in a worldwide epidemic. In contrast to Western medicine, Traditional Chinese medicine (TCM uses a holistic and synergistic approach to restore the balance of Yin-Yang of body energy so the body's normal function can be restored. Sini decoction (SND is a well-known formula of TCM which has been used to treat MI for many years. However, its holistic activity evaluation and mechanistic understanding are still lacking due to its complex components. METHODOLOGY/PRINCIPAL FINDINGS: A urinary metabonomic method based on nuclear magnetic resonance and ultra high-performance liquid chromatography coupled to mass spectrometry was developed to characterize MI-related metabolic profiles and delineate the effect of SND on MI. With Elastic Net for classification and selection of biomarkers, nineteen potential biomarkers in rat urine were screened out, primarily related to myocardial energy metabolism, including the glycolysis, citrate cycle, amino acid metabolism, purine metabolism and pyrimidine metabolism. With the altered metabolism pathways as possible drug targets, we systematically analyze the therapeutic effect of SND, which demonstrated that SND administration could provide satisfactory effect on MI through partially regulating the perturbed myocardial energy metabolism. CONCLUSIONS/SIGNIFICANCE: Our results showed that metabonomic approach offers a useful tool to identify MI-related biomarkers and provides a new methodological cue for systematically dissecting the underlying efficacies and mechanisms of TCM in treating MI.

  10. 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson's disease.

    Directory of Open Access Journals (Sweden)

    Jingjing Xu

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

  11. An NMR-based metabolomic approach to investigate the effects of supplementation with glutamic acid in piglets challenged with deoxynivalenol.

    Science.gov (United States)

    Wu, Miaomiao; Xiao, Hao; Ren, Wenkai; Yin, Jie; Hu, Jiayu; Duan, Jielin; Liu, Gang; Tan, Bie; Xiong, Xia; Oso, Abimbola Oladele; Adeola, Olayiwola; Yao, Kang; Yin, Yulong; Li, Tiejun

    2014-01-01

    Deoxynivalenol (DON) has various toxicological effects in humans and pigs that result from the ingestion of contaminated cereal products. This study was conducted to investigate the protective effects of dietary supplementation with glutamic acid on piglets challenged with DON. A total of 20 piglets weaned at 28 d of age were randomly assigned to receive 1 of 4 treatments (5 piglets/treatment): 1) basal diet, negative control (NC); 2) basal diet +4 mg/kg DON (DON); 3) basal diet +2% (g/g) glutamic acid (GLU); 4) basal diet +4 mg/kg DON +2% glutamic acid (DG). A 7-d adaptation period was followed by 30 days of treatment. A metabolite analysis using nuclear magnetic resonance spectroscopy (1H-NMR)-based metabolomic technology and the determination of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities for plasma, as well as the activity of Caspase-3 and the proliferation of epithelial cells were conducted. The results showed that contents of low-density lipoprotein, alanine, arginine, acetate, glycoprotein, trimethylamine-N-oxide (TMAO), glycine, lactate, and urea, as well as the glutamate/creatinine ratio were higher but high-density lipoprotein, proline, citrate, choline, unsaturated lipids and fumarate were lower in piglets of DON treatment than that of NC treatment (Pglutamic acid increased the plasma concentrations of proline, citrate, creatinine, unsaturated lipids, and fumarate, and decreased the concentrations of alanine, glycoprotein, TMAO, glycine, and lactate, as well as the glutamate/creatinine ratio (Pglutamic acid to DON treatment increased the plasma activities of SOD and GSH-Px and the proliferating cell nuclear antigen (PCNA) labeling indexes for the jejunum and ileum (Pglutamic acid has the potential to repair the injuries associated with oxidative stress as well as the disturbances of energy and amino acid metabolism induced by DON.

  12. Quantification of organic acids in beer by nuclear magnetic resonance (NMR)-based methods

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, J.E.A. [CICECO-Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Erny, G.L. [CESAM - Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Barros, A.S. [QOPNAA-Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Esteves, V.I. [CESAM - Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Brandao, T.; Ferreira, A.A. [UNICER, Bebidas de Portugal, Leca do Balio, 4466-955 S. Mamede de Infesta (Portugal); Cabrita, E. [Department of Chemistry, New University of Lisbon, 2825-114 Caparica (Portugal); Gil, A.M., E-mail: agil@ua.pt [CICECO-Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal)

    2010-08-03

    The organic acids present in beer provide important information on the product's quality and history, determining organoleptic properties and being useful indicators of fermentation performance. NMR spectroscopy may be used for rapid quantification of organic acids in beer and different NMR-based methodologies are hereby compared for the six main acids found in beer (acetic, citric, lactic, malic, pyruvic and succinic). The use of partial least squares (PLS) regression enables faster quantification, compared to traditional integration methods, and the performance of PLS models built using different reference methods (capillary electrophoresis (CE), both with direct and indirect UV detection, and enzymatic essays) was investigated. The best multivariate models were obtained using CE/indirect detection and enzymatic essays as reference and their response was compared with NMR integration, either using an internal reference or an electrical reference signal (Electronic REference To access In vivo Concentrations, ERETIC). NMR integration results generally agree with those obtained by PLS, with some overestimation for malic and pyruvic acids, probably due to peak overlap and subsequent integral errors, and an apparent relative underestimation for citric acid. Overall, these results make the PLS-NMR method an interesting choice for organic acid quantification in beer.

  13. Ameliorating effects of Mango (Mangifera indica L.) fruit on plasma ethanol level in a mouse model assessed with 1H-NMR based metabolic profiling

    Science.gov (United States)

    Kim, So-Hyun; K. Cho, Somi; Min, Tae-Sun; Kim, Yujin; Yang, Seung-Ok; Kim, Hee-Su; Hyun, Sun-Hee; Kim, Hana; Kim, Young-Suk; Choi, Hyung-Kyoon

    2011-01-01

    The ameliorating effects of Mango (Mangifera indica L.) flesh and peel samples on plasma ethanol level were investigated using a mouse model. Mango fruit samples remarkably decreased mouse plasma ethanol levels and increased the activities of alcohol dehydrogenase and acetaldehyde dehydrogenase. The 1H-NMR-based metabolomic technique was employed to investigate the differences in metabolic profiles of mango fruits, and mouse plasma samples fed with mango fruit samples. The partial least squares-discriminate analysis of 1H-NMR spectral data of mouse plasma demonstrated that there were clear separations among plasma samples from mice fed with buffer, mango flesh and peel. A loading plot demonstrated that metabolites from mango fruit, such as fructose and aspartate, might stimulate alcohol degradation enzymes. This study suggests that mango flesh and peel could be used as resources for functional foods intended to decrease plasma ethanol level after ethanol uptake. PMID:21562641

  14. Investigating correlations in the altered metabolic profiles of obese and diabetic subjects in a South Indian Asian population using an NMR-based metabolomic approach.

    Science.gov (United States)

    Gogna, Navdeep; Krishna, Murahari; Oommen, Anup Mammen; Dorai, Kavita

    2015-02-01

    It is well known that obesity/high body mass index (BMI) plays a key role in the evolution of insulin resistance and type-2 diabetes mellitus (T2DM). However, the exact mechanism underlying its contribution is still not fully understood. This work focuses on an NMR-based metabolomic investigation of the serum profiles of diabetic, obese South Indian Asian subjects. (1)H 1D and 2D NMR experiments were performed to profile the altered metabolic patterns of obese diabetic subjects and multivariate statistical methods were used to identify metabolites that contributed significantly to the differences in the samples of four different subject groups: diabetic and non-diabetic with low and high BMIs. Our analysis revealed that the T2DM-high BMI group has higher concentrations of saturated fatty acids, certain amino acids (leucine, isoleucine, lysine, proline, threonine, valine, glutamine, phenylalanine, histidine), lactic acid, 3-hydroxybutyric acid, choline, 3,7-dimethyluric acid, pantothenic acid, myoinositol, sorbitol, glycerol, and glucose, as compared to the non-diabetic-low BMI (control) group. Of these 19 identified significant metabolites, the levels of saturated fatty acids, lactate, valine, isoleucine, and phenylalanine are also higher in obese non-diabetic subjects as compared to control subjects, implying that this set of metabolites could be identified as potential biomarkers for the onset of diabetes in subjects with a high BMI. Our work validates the utility of NMR-based metabolomics in conjunction with multivariate statistical analysis to provide insights into the underlying metabolic pathways that are perturbed in diabetic subjects with a high BMI.

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

    Directory of Open Access Journals (Sweden)

    Miki Watanabe

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

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

    Science.gov (United States)

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

    2016-01-01

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

  17. NMR-based metabolomics for simultaneously evaluating multiple determinants of primary beef quality in Japanese Black cattle

    OpenAIRE

    Kodani, Yoshinori; Miyakawa, Takuya; Komatsu, Tomohiko; Tanokura, Masaru

    2017-01-01

    Analytical methodologies to comprehensively evaluate beef quality are increasingly needed to accelerate improvement in both breeding and post-mortem processing. Consumer palatability towards beef is generally attributed to tenderness, flavor, and/or juiciness. These primary qualities are modified by post-mortem aging and the crude content and fatty acid composition of intramuscular fat. In this study, we report a nuclear magnetic resonance (NMR)-based metabolic profiles of Japanese Black catt...

  18. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    International Nuclear Information System (INIS)

    Liu, Yansong; Xu, Dan; Feng, Jianghua; Kou, Hao; Liang, Gai; Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by 1 H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion

  19. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  20. Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally.

    Science.gov (United States)

    Kou, Hao; Liu, Yansong; Liang, Gai; Huang, Jing; Hu, Jieqiong; Yan, You-e; Li, Xiaojun; Yu, Hong; He, Xiaohua; Zhang, Baifang; Zhang, Yuanzhen; Feng, Jianghua; Wang, Hui

    2014-03-01

    Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180 mg/kg·d) from gestational days (GD) 11 to 20, or 180 mg/kg·d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose-effect study and on GD11, 14 and 17 in the time-course study were analyzed by ¹H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Urinary metabonomics study in a rat model in response to protein-energy malnutrition by using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Wu, Zeming; Li, Min; Zhao, Chunxia; Zhou, Jia; Chang, Yuwei; Li, Xiang; Gao, Peng; Lu, Xin; Li, Yousheng; Xu, Guowang

    2010-11-01

    Systematic studies were performed on the biological perturbations in metabolic phenotype responding to protein-energy malnutrition through global metabolic profiling analysis, in combination with pattern recognition. The malnutrition rat model was established through five weeks of strict diet restriction, and the metabonome data obtained from gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) were integrated to approximate the comprehensive metabolic signature. Principal component analysis and orthogonal projection to latent structure analysis were used for the classification of metabolic phenotypes and discovery of differentiating metabolites. The perturbations in the urine profiles of malnourished rats were marked by higher levels of creatine, threitol, pyroglutamic acid, gluconic acid and kynurenic acid, as well as decreased levels of succinic acid, cis-aconitic acid, citric acid, isocitric acid, threonic acid, trimethylglycine, N-methylnicotinic acid and uric acid. The alterations in these metabolites were associated with perturbations in energy metabolism, carbohydrate, amino acid, and fatty acid metabolism, purine metabolism, cofactor and vitamin metabolism, in response to protein and energy malnutrition. Our findings show the integration of GC-MS and LC-MS techniques for untargeted metabolic profiling analysis was promising for nutriology.

  2. HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase.

    Science.gov (United States)

    Evenäs, Johan; Edfeldt, Fredrik; Lepistö, Matti; Svitacheva, Naila; Synnergren, Anna; Lundquist, Britta; Gränse, Mia; Rönnholm, Anna; Varga, Mikael; Wright, John; Wei, Min; Yue, Sherrie; Wang, Junfeng; Li, Chong; Li, Xuan; Chen, Gang; Liao, Yong; Lv, Gang; Tjörnebo, Ann; Narjes, Frank

    2014-03-01

    The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign gave compound 41, a nanomolar inhibitor of hXO with efficacy in the hyperuricemic rat model after oral dosing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. A 1HNMR-Based Metabonomics Study of Postmenopausal Osteoporosis and Intervention Effects of Er-Xian Decoction in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Luping Qin

    2011-11-01

    Full Text Available A metabonomics method using 1H nuclear magnetic resonance spectroscopy (1HNMR was applied to obtain a systematic view of the development and progression of postmenopausal osteoporosis. Using partial least squares discriminant analysis (PLS-DA, 26 and 34 characteristic resonances were found respectively in urine and plasma of ovariectomized rats (Variable importance, VIP value ≥1.0, and the significant altered metabolites identified in the plasma and urine were 10 and 9, respectively. Changes in these metabolites were related to the pathways of lipid, energy and amino acid metabolism, some of which involved the oxidative system. The described method was also used to analyze the therapeutic effects of Er-Xian Decoction (EXD, a traditional Chinese medicine widely used in the clinical treatment of osteoporosis in China. The results showed that EXD administration could provide satisfactory effects on osteoporosis through partially regulating the perturbed pathways of lipid, energy and amino acid metabolism and improving the anti-oxidative ability.

  4. Effects of breviscapine on amyloid beta 1-42 induced Alzheimer's disease mice: A HPLC-QTOF-MS based plasma metabonomics study.

    Science.gov (United States)

    Xia, Hongjun; Wu, Lingling; Chu, Mengying; Feng, Huimin; Lu, Chunliang; Wang, Qinghe; He, Minghai; Ge, Xiaoqun

    2017-07-01

    Herba Erigerontis has long been used to cure apoplexy hemiplegia and precordial pain in China. In addition, the bioactivities of its total flavonoids-breviscapine included inhibiting amyloid beta (Aβ) fibril formation, antioxidation and metal chelating, which are beneficial to treat Alzheimer's disease (AD). Hence, A HPLC-QTOF-MS based plasma metabonomics approach was applied to investigate the neuroprotective effects of breviscapine on intracerebroventricular injection of aggregated Aβ 1-42 induced AD mice for the first time in the study. Ten potential biomarkers were screened out by multivariate statistical analysis, eight of which were further identified as indoleacrylic acid, C16 sphinganine, LPE (22:6), sulfolithocholic acid, LPC (16:0), PA (22:1/0:0), taurodeoxycholic acid, and PC (0:0/18:0). According to their metabolic pathways, it was supposed that breviscapine ameliorated the learning and memory deficits of AD mice predominantly by regulating phospholipids metabolism, elevating serotonin level and lowering cholesterols content in vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Di(2-ethylhexyl)phthalate Alters the Synthesis and β-Oxidation of Fatty Acids and Hinders ATP Supply in Mouse Testes via UPLC-Q-Exactive Orbitrap MS-Based Metabonomics Study.

    Science.gov (United States)

    Shen, Guolin; Zhou, Lili; Liu, Wei; Cui, Yuan; Xie, Wenping; Chen, Huiming; Yu, Wenlian; Li, Wentao; Li, Haishan

    2017-06-21

    Di(2-ethylhexyl) phthalate (DEHP) is considered to be an environmental endocrine disruptor at high levels of general exposure. Studies show that DEHP may cause testicular toxicity on human being. In this study, metabonomics techniques were used to identify differential endogenous metabolites, draw the network metabolic pathways, and conduct network analysis, to determine the underlying mechanisms of testicular toxicity induced by DEHP. The results showed that DEHP inhibited synthesis and accelerated β-oxidation of fatty acids and impaired the tricarboxylic acid cycle (TCA cycle) and gluconeogenesis, resulting in lactic acid accumulation and an insufficient ATP supply in the microenvironment of the testis. These alterations led to testicular atrophy and, thus, may be the underlying causes of testicular toxicity. DEHP also inhibited peroxisome proliferator activated receptors in the testis, which may be another potential reason for the testicular atrophy. These findings provided new insights to better understand the mechanisms of testicular toxicity induced by DEHP exposure.

  6. The urinary proteome and metabonome differ from normal in adults with mitochondrial disease.

    Science.gov (United States)

    Hall, Andrew M; Vilasi, Annalisa; Garcia-Perez, Isabel; Lapsley, Marta; Alston, Charlotte L; Pitceathly, Robert D S; McFarland, Robert; Schaefer, Andrew M; Turnbull, Doug M; Beaumont, Nick J; Hsuan, Justin J; Cutillas, Pedro R; Lindon, John C; Holmes, Elaine; Unwin, Robert J; Taylor, Robert W; Gorman, Grainne S; Rahman, Shamima; Hanna, Michael G

    2015-03-01

    We studied the extent and nature of renal involvement in a cohort of 117 adult patients with mitochondrial disease, by measuring urinary retinol-binding protein (RBP) and albumin; established markers of tubular and glomerular dysfunction, respectively. Seventy-five patients had the m.3243A>G mutation and the most frequent phenotypes within the entire cohort were 14 with MELAS, 33 with MIDD, and 17 with MERRF. Urinary RBP was increased in 29 of 75 of m.3243A>G patients, whereas albumin was increased in 23 of the 75. The corresponding numbers were 16 and 14, respectively, in the 42 non-m.3243A>G patients. RBP and albumin were higher in diabetic m.3243A>G patients than in nondiabetics, but there were no significant differences across the three major clinical phenotypes. The urine proteome (mass spectrometry) and metabonome (nuclear magnetic resonance) in a subset of the m.3243A>G patients were markedly different from controls, with the most significant alterations occurring in lysosomal proteins, calcium-binding proteins, and antioxidant defenses. Differences were also found between asymptomatic m.3243A>G carriers and controls. No patients had an elevated serum creatinine level, but 14% had hyponatremia, 10% had hypophosphatemia, and 14% had hypomagnesemia. Thus, abnormalities in kidney function are common in adults with mitochondrial disease, exist in the absence of elevated serum creatinine, and are not solely explained by diabetes.

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

    Science.gov (United States)

    Schock, Tracey B; Duke, Jessica; Goodson, Abby; Weldon, Daryl; Brunson, Jeff; Leffler, John W; Bearden, Daniel W

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Tracey B Schock

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

  9. NMR-based metabolomics for simultaneously evaluating multiple determinants of primary beef quality in Japanese Black cattle.

    Science.gov (United States)

    Kodani, Yoshinori; Miyakawa, Takuya; Komatsu, Tomohiko; Tanokura, Masaru

    2017-05-02

    Analytical methodologies to comprehensively evaluate beef quality are increasingly needed to accelerate improvement in both breeding and post-mortem processing. Consumer palatability towards beef is generally attributed to tenderness, flavor, and/or juiciness. These primary qualities are modified by post-mortem aging and the crude content and fatty acid composition of intramuscular fat. In this study, we report a nuclear magnetic resonance (NMR)-based metabolic profiles of Japanese Black cattle to evaluate the compositional attributes of intramuscular fat and the long-term post-mortem aging. The unsaturation degree of triacylglycerol was estimated by the 1 H NMR spectra and was correlated with the content ratio of unsaturated fatty acids (R 2  = 0.944) and the melting point of intramuscular fat (R 2  = 0.871). NMR-detected profiles of water-soluble metabolites revealed overall metabolic change (R 2  = 0.951) and several metabolites (R 2  > 0.818) linearly correlated with long-term aging duration, which can be used to evaluate the aging rate and aging duration of beef. This approach also provided the pH profile during aging, which is related to the water-holding capacity of beef. Thus, NMR-based metabolomics has the potential to evaluate multiple parameters related to the beef qualities of Japanese Black cattle.

  10. Evaluation of Pacific White Shrimp (Litopenaeus vannamei) Health during a Superintensive Aquaculture Growout Using NMR-Based Metabolomics

    Science.gov (United States)

    Schock, Tracey B.; Duke, Jessica; Goodson, Abby; Weldon, Daryl; Brunson, Jeff; Leffler, John W.; Bearden, Daniel W.

    2013-01-01

    Success of the shrimp aquaculture industry requires technological advances that increase production and environmental sustainability. Indoor, superintensive, aquaculture systems are being developed that permit year-round production of farmed shrimp at high densities. These systems are intended to overcome problems of disease susceptibility and of water quality issues from waste products, by operating as essentially closed systems that promote beneficial microbial communities (biofloc). The resulting biofloc can assimilate and detoxify wastes, may provide nutrition for the farmed organisms resulting in improved growth, and may aid in reducing disease initiated from external sources. Nuclear magnetic resonance (NMR)-based metabolomic techniques were used to assess shrimp health during a full growout cycle from the nursery phase through harvest in a minimal-exchange, superintensive, biofloc system. Aberrant shrimp metabolomes were detected from a spike in total ammonia nitrogen in the nursery, from a reduced feeding period that was a consequence of surface scum build-up in the raceway, and from the stocking transition from the nursery to the growout raceway. The biochemical changes in the shrimp that were induced by the stressors were essential for survival and included nitrogen detoxification and energy conservation mechanisms. Inosine and trehalose may be general biomarkers of stress in Litopenaeus vannamei. This study demonstrates one aspect of the practicality of using NMR-based metabolomics to enhance the aquaculture industry by providing physiological insight into common environmental stresses that may limit growth or better explain reduced survival and production. PMID:23555690

  11. Safety assessment of transgenic Bacillus thuringiensis rice T1c-19 in Sprague-Dawley rats from metabonomics and bacterial profile perspectives.

    Science.gov (United States)

    Cao, Sishuo; He, Xiaoyun; Xu, Wentao; Luo, YunBo; Yuan, Yanfang; Liu, Pengfei; Cao, Bo; Shi, Hui; Huang, Kunlun

    2012-03-01

    Bacillus thuringiensis rice is facing commercialization as the main food source in the near future. The unintended effects of genetically modified (GM) organisms are the most important barriers to their promotion. We aimed to establish a new in vivo evaluation model for genetically modified foods by using metabonomics and bacterial profile approaches. T1c-19 rice flour or its transgenic parent MH63 was used at 70% wt/wt to produce diets that were fed to rats for ∼ 90 days. Urine metabolite changes were detected using (1)H NMR. Denaturing gradient gel electrophoresis and real-time polymerase chain reaction (RT-PCR) were used to detect the bacterial profiles between the two groups. The metabonomics was analyzed for metabolite changes in rat urine, when compared with the non-GM rice group, where rats were fed a GM rice diet. Several metabolites correlated with rat age and sex but not with GM rice diet. Significant biological differences were not identified between the GM rice diet and the non-GM rice diet. The bacteria related to rat urine metabolites were also discussed. The results from metabonomics and bacterial profile analyses were comparable with the results attained using the traditional method. Because metabonomics and bacterial profiling offer noninvasive, dynamic approaches for monitoring food safety, they provide a novel process for assessing the safety of GM foods. Copyright © 2012 Wiley Periodicals, Inc.

  12. New Computational Approaches for NMR-based Drug Design: A Protocol for Ligand Docking to Flexible Target Sites

    International Nuclear Information System (INIS)

    Gracia, Luis; Speidel, Joshua A.; Weinstein, Harel

    2006-01-01

    NMR-based drug design has met with some success in the last decade, as illustrated in numerous instances by Fesik's ''ligand screening by NMR'' approach. Ongoing efforts to generalize this success have led us to the development of a new paradigm in which quantitative computational approaches are being integrated with NMR derived data and biological assays. The key component of this work is the inclusion of the intrinsic dynamic quality of NMR structures in theoretical models and its use in docking. A new computational protocol is introduced here, designed to dock small molecule ligands to flexible proteins derived from NMR structures. The algorithm makes use of a combination of simulated annealing monte carlo simulations (SA/MC) and a mean field potential informed by the NMR data. The new protocol is illustrated in the context of an ongoing project aimed at developing new selective inhibitors for the PCAF bromodomains that interact with HIV Tat

  13. The Use of Urine Proteomic and Metabonomic Patterns for the Diagnosis of Interstitial Cystitis and Bacterial Cystitis

    Directory of Open Access Journals (Sweden)

    Que N. Van

    2004-01-01

    Full Text Available The advent of systems biology approaches that have stemmed from the sequencing of the human genome has led to the search for new methods to diagnose diseases. While much effort has been focused on the identification of disease-specific biomarkers, recent efforts are underway toward the use of proteomic and metabonomic patterns to indicate disease. We have developed and contrasted the use of both proteomic and metabonomic patterns in urine for the detection of interstitial cystitis (IC. The methodology relies on advanced bioinformatics to scrutinize information contained within mass spectrometry (MS and high-resolution proton nuclear magnetic resonance (1H-NMR spectral patterns to distinguish IC-affected from non-affected individuals as well as those suffering from bacterial cystitis (BC. We have applied a novel pattern recognition tool that employs an unsupervised system (self-organizing-type cluster mapping as a fitness test for a supervised system (a genetic algorithm. With this approach, a training set comprised of mass spectra and 1H-NMR spectra from urine derived from either unaffected individuals or patients with IC is employed so that the most fit combination of relative, normalized intensity features defined at precise m/z or chemical shift values plotted in n-space can reliably distinguish the cohorts used in training. Using this bioinformatic approach, we were able to discriminate spectral patterns associated with IC-affected, BC-affected, and unaffected patients with a success rate of approximately 84%.

  14. Combined Metabonomic and Quantitative RT-PCR Analyses Revealed Metabolic Reprogramming Associated with Fusarium graminearum Resistance in Transgenic Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Fangfang Chen

    2018-01-01

    Full Text Available Fusarium head blight disease resulting from Fusarium graminearum (FG infection causes huge losses in global production of cereals and development of FG-resistant plants is urgently needed. To understand biochemistry mechanisms for FG resistance, here, we have systematically investigated the plant metabolomic phenotypes associated with FG resistance for transgenic Arabidopsis thaliana expressing a class-I chitinase (Chi, a Fusarium-specific recombinant antibody gene (CWP2 and fused Chi-CWP2. Plant disease indices, mycotoxin levels, metabonomic characteristics, and expression levels of several key genes were measured together with their correlations. We found that A. thaliana expressing Chi-CWP2 showed higher FG resistance with much lower disease indices and mycotoxin levels than the wild-type and the plants expressing Chi or CWP2 alone. The combined metabonomic and quantitative RT-PCR analyses revealed that such FG-resistance was closely associated with the promoted biosynthesis of secondary metabolites (phenylpropanoids, alkanoids and organic osmolytes (proline, betaine, glucose, myo-inositol together with enhanced TCA cycle and GABA shunt. These suggest that the concurrently enhanced biosyntheses of the shikimate-mediated secondary metabolites and organic osmolytes be an important strategy for A. thaliana to develop and improve FG resistance. These findings provide essential biochemical information related to FG resistance which is important for developing FG-resistant cereals.

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

  17. NMR-based detection of hydrogen/deuterium exchange in liposome-embedded membrane proteins.

    Directory of Open Access Journals (Sweden)

    Xuejun Yao

    Full Text Available Membrane proteins play key roles in biology. Determination of their structure in a membrane environment, however, is highly challenging. To address this challenge, we developed an approach that couples hydrogen/deuterium exchange of membrane proteins to rapid unfolding and detection by solution-state NMR spectroscopy. We show that the method allows analysis of the solvent protection of single residues in liposome-embedded proteins such as the 349-residue Tom40, the major protein translocation pore in the outer mitochondrial membrane, which has resisted structural analysis for many years.

  18. NMR-Based Metabolic Profiling of Field-Grown Leaves from Sugar Beet Plants Harbouring Different Levels of Resistance to Cercospora Leaf Spot Disease

    Science.gov (United States)

    Sekiyama, Yasuyo; Okazaki, Kazuyuki; Kikuchi, Jun; Ikeda, Seishi

    2017-01-01

    Cercospora leaf spot (CLS) is one of the most serious leaf diseases for sugar beet (Beta vulgaris L.) worldwide. The breeding of sugar beet cultivars with both high CLS resistance and high yield is a major challenge for breeders. In this study, we report the nuclear magnetic resonance (NMR)-based metabolic profiling of field-grown leaves for a subset of sugar beet genotypes harbouring different levels of CLS resistance. Leaves were collected from 12 sugar beet genotypes at four time points: seedling, early growth, root enlargement, and disease development stages. 1H-NMR spectra of foliar metabolites soluble in a deuterium-oxide (D2O)-based buffer were acquired and subjected to multivariate analyses. A principal component analysis (PCA) of the NMR data from the sugar beet leaves shows clear differences among the growth stages. At the later time points, the sugar and glycine betaine contents were increased, whereas the choline content was decreased. The relationship between the foliar metabolite profiles and resistance level to CLS was examined by combining partial least squares projection to latent structure (PLS) or orthogonal PLS (OPLS) analysis and univariate analyses. It was difficult to build a robust model for predicting precisely the disease severity indices (DSIs) of each genotype; however, GABA and Gln differentiated susceptible genotypes (genotypes with weak resistance) from resistant genotypes (genotypes with resistance greater than a moderate level) before inoculation tests. The results suggested that breeders might exclude susceptible genotypes from breeding programs based on foliar metabolites profiled without inoculation tests, which require an enormous amount of time and effort. PMID:28134762

  19. NMR-Based Metabolic Profiling of Field-Grown Leaves from Sugar Beet Plants Harbouring Different Levels of Resistance to Cercospora Leaf Spot Disease

    Directory of Open Access Journals (Sweden)

    Yasuyo Sekiyama

    2017-01-01

    Full Text Available Cercospora leaf spot (CLS is one of the most serious leaf diseases for sugar beet (Beta vulgaris L. worldwide. The breeding of sugar beet cultivars with both high CLS resistance and high yield is a major challenge for breeders. In this study, we report the nuclear magnetic resonance (NMR-based metabolic profiling of field-grown leaves for a subset of sugar beet genotypes harbouring different levels of CLS resistance. Leaves were collected from 12 sugar beet genotypes at four time points: seedling, early growth, root enlargement, and disease development stages. 1H-NMR spectra of foliar metabolites soluble in a deuterium-oxide (D2O-based buffer were acquired and subjected to multivariate analyses. A principal component analysis (PCA of the NMR data from the sugar beet leaves shows clear differences among the growth stages. At the later time points, the sugar and glycine betaine contents were increased, whereas the choline content was decreased. The relationship between the foliar metabolite profiles and resistance level to CLS was examined by combining partial least squares projection to latent structure (PLS or orthogonal PLS (OPLS analysis and univariate analyses. It was difficult to build a robust model for predicting precisely the disease severity indices (DSIs of each genotype; however, GABA and Gln differentiated susceptible genotypes (genotypes with weak resistance from resistant genotypes (genotypes with resistance greater than a moderate level before inoculation tests. The results suggested that breeders might exclude susceptible genotypes from breeding programs based on foliar metabolites profiled without inoculation tests, which require an enormous amount of time and effort.

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

    Science.gov (United States)

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

    2015-03-01

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

  1. Harvest year effects on Apulian EVOOs evaluated by1H NMR based metabolomics.

    Science.gov (United States)

    Girelli, Chiara R; Del Coco, Laura; Papadia, Paride; De Pascali, Sandra A; Fanizzi, Francesco P

    2016-01-01

    Nine hundred extra virgin olive oils (EVOO) were extracted from individual olive trees of four olive cultivars (Coratina, Cima di Mola, Ogliarola, Peranzana), originating from the provinces of Bari and Foggia (Apulia region, Southern Italy) and collected during two consecutive harvesting seasons (2013/14 and 2014/15). Following genetic identification of individual olive trees, a detailed Apulian EVOO NMR database was built using 900 oils samples obtained from 900 cultivar certified single trees. A study on the olive oil lipid profile was carried out by statistical multivariate analysis (Principal Component Analysis, PCA, Partial Least-Squares Discriminant Analysis, PLS-DA, Orthogonal Partial Least-Squares Discriminant Analysis, OPLS-DA). Influence of cultivar and weather conditions, such as the summer rainfall, on the oil metabolic profile have been evaluated. Mahalanobis distances and J 2 criterion have been measured to assess the quality of resulting scores clusters for each cultivar in the two harvesting campaigns. The four studied cultivars showed non homogeneous behavior. Notwithstanding the geographical spread and the wide number of samples, Coratina showed a consistent behavior of its metabolic profile in the two considered harvests. Among the other three Peranzana showed the second more consistent behavior, while Cima di Mola and Ogliarola having the biggest change over the two years.

  2. STD-NMR-Based Protein Engineering of the Unique Arylpropionate-Racemase AMDase G74C.

    Science.gov (United States)

    Gaßmeyer, Sarah Katharina; Yoshikawa, Hiroyuki; Enoki, Junichi; Hülsemann, Nadine; Stoll, Raphael; Miyamoto, Kenji; Kourist, Robert

    2015-06-23

    Structure-guided protein engineering achieved a variant of the unique racemase AMDase G74C, with 40-fold increased activity in the racemisation of several arylaliphatic carboxylic acids. Substrate binding during catalysis was investigated by saturation-transfer-difference NMR (STD-NMR) spectroscopy. All atoms of the substrate showed interactions with the enzyme. STD-NMR measurements revealed distinct nuclear Overhauser effects in experiments with and without molecular conversion. The spectroscopic analysis led to the identification of several amino acid residues whose substitutions increased the activity of G74C. Single amino acid exchanges increased the activity moderately; structure-guided saturation mutagenesis yielded a quadruple mutant with a 40 times higher reaction rate. This study presents STD-NMR as versatile tool for the analysis of enzyme-substrate interactions in catalytically competent systems and for the guidance of protein engineering. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Geometric quantum gates in liquid-state NMR based on a cancellation of dynamical phases

    Science.gov (United States)

    Ota, Yukihiro; Goto, Yoshito; Kondo, Yasushi; Nakahara, Mikio

    2009-11-01

    A proposal for applying nonadiabatic geometric phases to quantum computing, called double-loop method [S.-L. Zhu and Z. D. Wang, Phys. Rev. A 67, 022319 (2003)], is demonstrated in a liquid-state nuclear magnetic-resonance quantum computer. Using a spin-echo technique, the original method is modified so that quantum gates are implemented in a standard high-precision nuclear magnetic-resonance system for chemical analysis. We show that a dynamical phase is successfully eliminated and a one-qubit quantum gate is realized although the gate fidelity is not high.

  4. 1H-13C NMR-based profiling of biotechnological starch utilization

    DEFF Research Database (Denmark)

    Sundekilde, Ulrik K.; Meier, Sebastian

    2016-01-01

    Starch is used in food-and non-food applications as a renewable and degradable source of carbon and energy. Insight into the chemical detail of starch degradation remains challenging as the starch constituents amylose and amylopectin are homopolymers. We show that considerable molecular detail...... of starch fragmentation can be obtained from multivariate analysis of spectral features in optimized 1H-13C NMR spectroscopy of starch fragments to identify relevant features that distinguish processes in starch utilization. As a case study, we compare the profiles of starch fragments in commercial beer...... samples. Spectroscopic profiles of homooligomeric starch fragments can be excellent indicators of process conditions. In addition, differences in the structure and composition of starch fragments have predictive value for down-stream process output such as ethanol production from starch. Thus, high...

  5. 1H NMR- based metabolite profiling of tropane alkaloids in Duboisia spec.

    Directory of Open Access Journals (Sweden)

    Ullrich, Sophie Friederike

    2016-07-01

    Full Text Available Duboisia R.Br. (Solanaceae is the main source of the tropane alkaloid scopolamine, which is an important precursor of various active pharmaceutical ingredients due to its anticholinergic properties. As only little is known about the metabolite composition among the different species, NMRbased metabolic profiling was done in order to elucidate primary and secondary metabolism in Duboisia especially focusing on the tropane alkaloid pathway. For this purpose, plants of five different genotypes (Duboisia myoporoides, D. leichardtii and hybrids of D. myoporoides and D. leichhardtii were cultivated under strictly controlled conditions in climate chambers, leaf and root extracts were prepared and measured via 1H NMR. 14 different metabolites could be identified using 1D- and 2D-NMR techniques. Principal component analysis of the NMR data allowed a clear distinction between Duboisia hybrids and the wild types, which could be again subgrouped in D. myoporoides and D. leichhardtii, based on the metabolites identified.

  6. 1H NMR based metabolic profiling of eleven Algerian aromatic plants and evaluation of their antioxidant and cytotoxic properties.

    Science.gov (United States)

    Brahmi, Nabila; Scognamiglio, Monica; Pacifico, Severina; Mekhoukhe, Aida; Madani, Khodir; Fiorentino, Antonio; Monaco, Pietro

    2015-10-01

    Eleven Algerian medicinal and aromatic plants (Aloysia triphylla, Apium graveolens, Coriandrum sativum, Laurus nobilis, Lavandula officinalis, Marrubium vulgare, Mentha spicata, Inula viscosa, Petroselinum crispum, Salvia officinalis, and Thymus vulgaris) were selected and their hydroalcoholic extracts were screened for their antiradical and antioxidant properties in cell-free systems. In order to identify the main metabolites constituting the extracts, 1 H NMR-based metabolic profiling was applied. Data obtained emphasized the antiradical properties of T. vulgaris, M. spicata and L. nobilis extracts (RACI 1.37, 0.97 and 0.93, respectively), whereas parsley was the less active as antioxidant (RACI -1.26). When the cytotoxic effects of low and antioxidant doses of each extract were evaluated towards SK-N-BE(2)C neuronal and HepG2 hepatic cell lines, it was observed that all the extracts weakly affected the metabolic redox activity of the tested cell lines. Overall, data strongly plead in favor of the use of these plants as potential food additives in replacement of synthetic compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-11-15

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

  8. Metabolic Effect of Dietary Taurine Supplementation on Nile Tilapia (Oreochromis nilotictus) Evaluated by NMR-Based Metabolomics.

    Science.gov (United States)

    Shen, Guiping; Huang, Ying; Dong, Jiyang; Wang, Xuexi; Cheng, Kian-Kai; Feng, Jianghua; Xu, Jingjing; Ye, Jidan

    2018-01-10

    Taurine is indispensable in aquatic diets that are based solely on plant protein, and it promotes growth of many fish species. However, the physiological and metabolome effects of taurine on fish have not been well described. In this study, 1 H NMR-based metabolomics approaches were applied to investigate the metabolite variations in Nile tilapia (Oreochromis nilotictus) muscle in order to visualize the metabolic trajectory and reveal the possible mechanisms of metabolic effects of dietary taurine supplementation on tilapia growth. After extraction using aqueous and organic solvents, 19 taurine-induced metabolic changes were evaluated in our study. The metabolic changes were characterized by differences in carbohydrate, amino acid, lipid, and nucleotide contents. The results indicate that taurine supplementation could significantly regulate the physiological state of fish and promote growth and development. These results provide a basis for understanding the mechanism of dietary taurine supplementation in fish feeding. 1 H NMR spectroscopy, coupled with multivariate pattern recognition technologies, is an efficient and useful tool to map the fish metabolome and identify metabolic responses to different dietary nutrients in aquaculture.

  9. Comparison of Chemical Compositions in Pseudostellariae Radix from Different Cultivated Fields and Germplasms by NMR-Based Metabolomics

    Directory of Open Access Journals (Sweden)

    Yujiao Hua

    2016-11-01

    Full Text Available Pseudostellariae Radix (PR is an important traditional Chinese medicine (TCM, which is consumed commonly for its positive health effects. However, the chemical differences of PR from different cultivated fields and germplasms are still unknown. In order to comprehensively compare the chemical compositions of PR from different cultivated fields, in this study, 1H-NMR-based metabolomics coupled with high performance liquid chromatography (HPLC were used to investigate the different metabolites in PR from five germplasms (jr, zs1, zs2, sb, and xc cultivated in traditional fields (Jurong, Jiangsu, JSJR and cultivated fields (Zherong, Fujian, FJZR. A total of 34 metabolites were identified based on 1H-NMR data, and fourteen of them were found to be different in PR from JSJR and FJZR. The relative contents of alanine, lactate, lysine, taurine, sucrose, tyrosine, linolenic acid, γ-aminobutyrate, and hyperoside in PR from JSJR were higher than that in PR from FJZR, while PR from FJZR contained higher levels of glutamine, raffinose, xylose, unsaturated fatty acid, and formic acid. The contents of Heterophyllin A and Heterophyllin B were higher in PR from FJZR. This study will provide the basic information for exploring the influence law of ecological environment and germplasm genetic variation on metabolite biosynthesis of PR and its quality formation mechanism.

  10. PINE-SPARKY.2 for automated NMR-based protein structure research.

    Science.gov (United States)

    Lee, Woonghee; Markley, John L

    2018-05-01

    Nuclear magnetic resonance (NMR) spectroscopy, along with X-ray crystallography and cryoelectron microscopy, is one of the three major tools that enable the determination of atomic-level structural models of biological macromolecules. Of these, NMR has the unique ability to follow important processes in solution, including conformational changes, internal dynamics and protein-ligand interactions. As a means for facilitating the handling and analysis of spectra involved in these types of NMR studies, we have developed PINE-SPARKY.2, a software package that integrates and automates discrete tasks that previously required interaction with separate software packages. The graphical user interface of PINE-SPARKY.2 simplifies chemical shift assignment and verification, automated detection of secondary structural elements, predictions of flexibility and hydrophobic cores, and calculation of three-dimensional structural models. PINE-SPARKY.2 is available in the latest version of NMRFAM-SPARKY from the National Magnetic Resonance Facility at Madison (http://pine.nmrfam.wisc.edu/download_packages.html), the NMRbox Project (https://nmrbox.org) and to subscribers to the SBGrid (https://sbgrid.org). For a detailed description of the program, see http://www.nmrfam.wisc.edu/pine-sparky2.htm. whlee@nmrfam.wisc.edu or markley@nmrfam.wisc.edu. Supplementary data are available at Bioinformatics online.

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

    Science.gov (United States)

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

    2009-10-15

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

  12. NMR-based metabolomics of water-buffalo milk after conventional or biological feeding

    Directory of Open Access Journals (Sweden)

    Pierluigi Mazzei

    2018-02-01

    Full Text Available Abstract Background Biological farming in dairy production is often advocated as one of the most virtuous solutions to the environmental problems of conventional farming while improving the sustainability of production and cattle welfare. However, it is still under debate whether the conversion from conventional to biological farming has an influence on milk composition. In addition, the possible frauds related to biological dairy products call for analytical tools enabling the authentication of products quality and consumers protection. The aim of this work was to determine the composition of milk produced by water-buffaloes and to identify the specific metabolic profiles discriminating a biological from a conventional feeding diet. Methods Liquid-state 1H, 13C, and 31P nuclear magnetic resonance (NMR spectroscopies were used to study milk samples which were supplied during a 2-year-long experimentation by a single dairy farm and sampled from conventionally and biologically fed buffaloes (CFM and BFM, respectively. For each milk sample, we obtained NMR spectra of both raw milk and milk cream fractions comprising neutral lipids and phospholipids. Results The elaboration of multinuclear spectroscopic NMR results by the principal component analysis (PCA enabled the identification of diagnostic differences in the milk composition between CFM and BFM samples. In particular, BFM were characterized by larger content of unsaturated lipids and phosphatidylcholine. Our findings confirmed that the conversion from a conventional to biological feeding regime influenced the buffalo milk composition, with possible implications for sensorial and nutritional properties of dairy products. Finally, the analytical methodology of NMR spectroscopy shown here may be considered as a useful tool to assess the quality and the authenticity of biological milk.

  13. NMR-based approach to measure the free energy of transmembrane helix-helix interactions.

    Science.gov (United States)

    Mineev, Konstantin S; Lesovoy, Dmitry M; Usmanova, Dinara R; Goncharuk, Sergey A; Shulepko, Mikhail A; Lyukmanova, Ekaterina N; Kirpichnikov, Mikhail P; Bocharov, Eduard V; Arseniev, Alexander S

    2014-01-01

    Knowledge of the energetic parameters of transmembrane helix-helix interactions is necessary for the establishment of a structure-energy relationship for α-helical membrane domains. A number of techniques have been developed to measure the free energies of dimerization and oligomerization of transmembrane α-helices, and all of these have their advantages and drawbacks. In this study we propose a methodology to determine the magnitudes of the free energy of interactions between transmembrane helices in detergent micelles. The suggested approach employs solution nuclear magnetic resonance (NMR) spectroscopy to determine the population of the oligomeric states of the transmembrane domains and introduces a new formalism to describe the oligomerization equilibrium, which is based on the assumption that both the dimerization of the transmembrane domains and the dissociation of the dimer can occur only upon the collision of detergent micelles. The technique has three major advantages compared with other existing approaches: it may be used to analyze both weak and relatively strong dimerization/oligomerization processes, it works well for the analysis of complex equilibria, e.g. when monomer, dimer and high-order oligomer populations are simultaneously present in the solution, and it can simultaneously yield both structural and energetic characteristics of the helix-helix interaction under study. The proposed methodology was applied to investigate the oligomerization process of transmembrane domains of fibroblast growth factor receptor 3 (FGFR3) and vascular endothelium growth factor receptor 2 (VEGFR2), and allowed the measurement of the free energy of dimerization of both of these objects. In addition the proposed method was able to describe the multi-state oligomerization process of the VEGFR2 transmembrane domain. © 2013 Elsevier B.V. All rights reserved.

  14. Lactose Binding Induces Opposing Dynamics Changes in Human Galectins Revealed by NMR-Based Hydrogen-Deuterium Exchange.

    Science.gov (United States)

    Chien, Chih-Ta Henry; Ho, Meng-Ru; Lin, Chung-Hung; Hsu, Shang-Te Danny

    2017-08-16

    Galectins are β-galactoside-binding proteins implicated in a myriad of biological functions. Despite their highly conserved carbohydrate binding motifs with essentially identical structures, their affinities for lactose, a common galectin inhibitor, vary significantly. Here, we aimed to examine the molecular basis of differential lactose affinities amongst galectins using solution-based techniques. Consistent dissociation constants of lactose binding were derived from nuclear magnetic resonance (NMR) spectroscopy, intrinsic tryptophan fluorescence, isothermal titration calorimetry and bio-layer interferometry for human galectin-1 (hGal1), galectin-7 (hGal7), and the N-terminal and C-terminal domains of galectin-8 (hGal8 NTD and hGal8 CTD , respectively). Furthermore, the dissociation rates of lactose binding were extracted from NMR lineshape analyses. Structural mapping of chemical shift perturbations revealed long-range perturbations upon lactose binding for hGal1 and hGal8 NTD . We further demonstrated using the NMR-based hydrogen-deuterium exchange (HDX) that lactose binding increases the exchange rates of residues located on the opposite side of the ligand-binding pocket for hGal1 and hGal8 NTD , indicative of allostery. Additionally, lactose binding induces significant stabilisation of hGal8 CTD across the entire domain. Our results suggested that lactose binding reduced the internal dynamics of hGal8 CTD on a very slow timescale (minutes and slower) at the expense of reduced binding affinity due to the unfavourable loss of conformational entropy.

  15. Characterization of Chinese Liquor Starter, ''Daqu", by Flavor Type with H-1 NMR-Based Nontargeted Analysis.

    NARCIS (Netherlands)

    Wu, X.H.; Zheng, X.; Han, B.Z.; Vervoort, J.J.M.; Nout, M.J.R.

    2009-01-01

    "Daqu" is a fermentation starter and substrate complex that is used to initiate fermentations for the production of Chinese liquor (alcoholic spirit). Several different types of Daqu are customary used, having different flavours, i.e. light, strong, or sauce flavor. With the aim to develop objective

  16. Safety assessment of genetically modified rice expressing human serum albumin from urine metabonomics and fecal bacterial profile.

    Science.gov (United States)

    Qi, Xiaozhe; Chen, Siyuan; Sheng, Yao; Guo, Mingzhang; Liu, Yifei; He, Xiaoyun; Huang, Kunlun; Xu, Wentao

    2015-02-01

    The genetically modified (GM) rice expressing human serum albumin (HSA) is used for non-food purposes; however, its food safety assessment should be conducted due to the probability of accidental mixture with conventional food. In this research, Sprague Dawley rats were fed diets containing 50% (wt/wt) GM rice expressing HSA or non-GM rice for 90 days. Urine metabolites were detected by (1)H NMR to examine the changes of the metabolites in the dynamic process of metabolism. Fecal bacterial profiles were detected by denaturing gradient gel electrophoresis to reflect intestinal health. Additionally, short chain fatty acids and fecal enzymes were investigated. The results showed that compared with rats fed the non-GM rice, some significant differences were observed in rats fed with the GM rice; however, these changes were not significantly different from the control diet group. Additionally, the gut microbiota was associated with blood indexes and urine metabolites. In conclusion, the GM rice diet is as safe as the traditional daily diet. Furthermore, urine metabonomics and fecal bacterial profiles provide a non-invasive food safety assessment rat model for genetically modified crops that are used for non-food/feed purposes. Fecal bacterial profiles have the potential for predicting the change of blood indexes in future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Metabonomics in Ulcerative Colitis: Diagnostics, Biomarker Identification, And Insight into the Pathophysiology

    DEFF Research Database (Denmark)

    Bjerrum, Jacob T; Nielsen, Ole H; Hao, Fuhua

    2010-01-01

    Nuclear magnetic resonance (NMR) spectroscopy and appropriate multivariate statistical analyses have been employed on mucosal colonic biopsies, colonocytes, lymphocytes, and urine from patients with ulcerative colitis (UC) and controls in order to explore the diagnostic possibilities, define new...... potential biomarkers, and generate a better understanding of the pathophysiology. Samples were collected from patients with active UC (n = 41), quiescent UC (n = 33), and from controls (n = 25) and analyzed by NMR spectroscopy. Data analysis was carried out by principal component analysis and orthogonal......-projection to latent structure-discriminant analysis using the SIMCA P+11 software package (Umetrics, Umea, Sweden) and Matlab environment. Significant differences between controls and active UC were discovered in the metabolic profiles of biopsies and colonocytes. In the biopsies from patients with active UC higher...

  18. {sup 1}H-NMR-based metabolomics studies of the toxicity of mesoporous carbon nanoparticles in Zebrafish (Daniorerio)

    Energy Technology Data Exchange (ETDEWEB)

    Raja, Ganesan; Kim, Si Won; Yoon, Da Hye; Yoon, Chang Shin; Kim, Suhkmann [Dept. of Chemistry, Center for Proteome Biophysics and Chemistry Institute for Functional Materials, Pusan National University, Busan (Korea, Republic of)

    2017-02-15

    Mesoporous carbon nanoparticles (MCNs) have been applied in a variety of drug/gene carriers. In addition to their potential benefits, many studies of their potential toxicity have been reported, showing the limitations of metabolic contextualization. In this study, we conducted {sup 1}H-nuclear magnetic resonance (NMR) profiling combined with statistical methods such as orthogonal partial least squares discriminant analysis and Pearson correlation analysis to assess metabolic alterations in the whole body of zebrafish (Danio rerio) in the presence of various concentrations of MCNs. The MCN exposure influenced numerous metabolites in energy metabolism (e.g., metabolites involved in glycolysis and tricarboxylic acid cycle) and disturbed the balance of neurotransmitters and osmoregulators. Our findings demonstrate the potential applicability of using a metabolomics approach to determine underlying metabolic disturbances caused by MCNs.

  19. NMR-based plasma metabolomic discrimination for male fertility assessment of rats treated with Eurycoma longifolia extracts.

    Science.gov (United States)

    Ebrahimi, Forough; Ibrahim, Baharudin; Teh, Chin-Hoe; Murugaiyah, Vikneswaran; Chan, Kit-Lam

    2017-06-01

    Male infertility is one of the leading causes of infertility which affects many couples worldwide. Semen analysis is a routine examination of male fertility status which is usually performed on semen samples obtained through masturbation that may be inconvenient to patients. Eurycoma longifolia (Tongkat Ali, TA), native to Malaysia, has been traditionally used as a remedy to boost male fertility. In our recent studies in rats, upon the administration of high-quassinoid content extracts of TA including TA water (TAW), quassinoid-rich TA (TAQR) extracts, and a low-quassinoid content extract including quassinoid-poor TA (TAQP) extract, sperm count (SC) increased in TAW- and TAQR-treated rats when compared to the TAQP-treated and control groups. Consequently, the rats were divided into normal- (control and TAQP-treated) and high- (TAW- and TAQR-treated) SC groups [Ebrahimi et al. 2016]. Post-treatment rat plasma was collected. An optimized plasma sample preparation method was developed with respect to the internal standards sodium 3- (trimethylsilyl) propionate- 2,2,3,3- d4 (TSP) and deuterated 4-dimethyl-4-silapentane-1-ammonium trifluoroacetate (DSA). Carr-Purcell-Meibum-Gill (CPMG) experiments combined with orthogonal partial least squares discriminant analysis (OPLS-DA) was employed to evaluate plasma metabolomic changes in normal- and high-SC rats. The potential biomarkers associated with SC increase were investigated to assess fertility by capturing the metabolomic profile of plasma. DSA was selected as the optimized internal standard for plasma analysis due to its significantly smaller half-height line width (W h/2 ) compared to that of TSP. The validated OPLS-DA model clearly discriminated the CPMG profiles in regard to the SC level. Plasma profiles of the high-SC group contained higher levels of alanine, lactate, and histidine, while ethanol concentration was significantly higher in the normal-SC group. This approach might be a new alternative applicable to

  20. Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Steenholdt, Casper; Ainsworth, Mark

    2017-01-01

    with principal components analysis and orthogonal projection to latent structures discriminant analysis using SIMCA-P+ v12 and MATLAB. Results: Metabolic profiles were significantly different between active ulcerative colitis and controls, active Crohn's disease and controls, and quiescent Crohn's disease...... changes taking place during induction treatment with IFX. Of distinct clinical relevance is the identification of a reversible proatherogenic lipid profile in IBD patients with active disease, which partially explains the increased risk of cardiovascular disease associated with IBD.......Background: One-third of inflammatory bowel disease (IBD) patients show no response to infliximab (IFX) induction therapy, and approximately half of patients responding become unresponsive over time. Thus, identification of potential treatment response biomarkers are of great clinical significance...

  1. Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn's disease and healthy individuals

    DEFF Research Database (Denmark)

    Bjerrum, Jacob Tveiten; Wang, Yulan; Hao, Fuhua

    2015-01-01

    This study employs spectroscopy-based metabolic profiling of fecal extracts from healthy subjects and patients with active or inactive ulcerative colitis (UC) and Crohn's disease (CD) to substantiate the potential use of spectroscopy as a non-invasive diagnostic tool and to characterize the fecal...... metabolome in inflammatory bowel disease (IBD). Stool samples from 113 individuals (UC 48, CD 44, controls 21) were analyzed by (1)H nuclear magnetic resonance (NMR) spectroscopy (Bruker 600 MHz, Bruker BioSpin, Rheinstetten, Germany). Data were analyzed with principal component analysis and orthogonal......-projection to latent structure-discriminant analysis using SIMCA-P + 12 and MATLAB. Significant differences were found in the metabolic profiles making it possible to differentiate between active IBD and controls and between UC and CD. The metabolites holding differential power primarily belonged to a range of amino...

  2. Plasma, urine and ligament tissue metabolite profiling reveals potential biomarkers of ankylosing spondylitis using NMR-based metabolic profiles.

    Science.gov (United States)

    Wang, Wei; Yang, Gen-Jin; Zhang, Ju; Chen, Chen; Jia, Zhen-Yu; Li, Jia; Xu, Wei-Dong

    2016-10-22

    Ankylosing spondylitis (AS) is an autoimmune rheumatic disease mostly affecting the axial skeleton. Currently, anti-tumour necrosis factor α (anti-TNF-α) represents an effective treatment for AS that may delay the progression of the disease and alleviate the symptoms if the diagnosis can be made early. Unfortunately, effective diagnostic biomarkers for AS are still lacking; therefore, most patients with AS do not receive timely and effective treatment. The intent of this study was to determine several key metabolites as potential biomarkers of AS using metabolomic methods to facilitate the early diagnosis of AS. First, we collected samples of plasma, urine, and ligament tissue around the hip joint from AS and control groups. The samples were examined by nuclear magnetic resonance spectrometry, and multivariate data analysis was performed to find metabolites that differed between the groups. Subsequently, according to the correlation coefficients, variable importance for the projection (VIP) and P values of the metabolites obtained in the multivariate data analysis, the most crucial metabolites were selected as potential biomarkers of AS. Finally, metabolic pathways involving the potential biomarkers were determined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and the metabolic pathway map was drawn. Forty-four patients with AS agreed to provide plasma and urine samples, and 30 provided ligament tissue samples. An equal number of volunteers were recruited for the control group. Multidimensional statistical analysis suggested significant differences between the patients with AS and control subjects, and the models exhibited good discrimination and predictive ability. A total of 20 different metabolites ultimately met the requirements for potential biomarkers. According to KEGG analysis, these marker metabolites were primarily related to fat metabolism, intestinal microbial metabolism, glucose metabolism and choline metabolism pathways, and

  3. New dereplication method applied to NMR-Based metabolomics on different fusarium species isolated from Rhizosphere of Senna spectabilis

    Energy Technology Data Exchange (ETDEWEB)

    Selegato, Denise M.; Castro-Gamboa, Ian, E-mail: ian.castro@gmail.com [Universidade Estadual Paulista Júlio de Mesquita Filho (NuBBE/UNESP), Araraquara, SP (Brazil). Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais; Freire, Rafael T.; Tannús, Alberto [Universidade de São Paulo (CIERMag/USP), São Carlos, SP (Brazil). Centro de Imagens e Espectroscopia in Vivo por Ressonância Magnética

    2016-07-01

    The search for new sources of natural products steadily increased the use of bioinformatics tools that enabled efficient analysis of complex matrices. In this context, dereplication methods emerged as a fast way of identifying known compounds, accelerating the identification of bioactive chemotypes. Although {sup 1}H NMR is widely used as an analytical technique, few studies have been reported using it as a dereplication tool, primarily because of the spectral complexity. This work aims to create a new computational method that analyses {sup 1}H NMR data from Fusarium solani and F. oxysporum isolated from Senna spectabilis' srhizosphere through principal component analysis (PCA). The algorithm uses loading values to select important peaks that distinguish both species in PCA, allowing compound dereplication, even in highly similar profiles. As a result, the method, associated with other NMR experiments and information from an in-house Fusarium's metabolite library was able to distinguish different mycotoxins produced by both fungi, identifying fusaric acid and beauvericin for F. oxysporum and the depsipeptide HA23 from F. solani. (author)

  4. Targeted isolation and identification of bioactive compounds lowering cholesterol in the crude extracts of crabapples using UPLC-DAD-MS-SPE/NMR based on pharmacology-guided PLS-DA.

    Science.gov (United States)

    Wen, Chao; Wang, Dongshan; Li, Xing; Huang, Tao; Huang, Cheng; Hu, Kaifeng

    2018-02-20

    The anti-hyperlipidemic effects of crude crabapple extracts derived from Malus 'Red jade', Malus hupehensis (Pamp.) Rehd. and Malus prunifolia (Willd.) Borkh. were evaluated on high-fat diet induced obese (HF DIO) mice. The results revealed that some of these extracts could lower serum cholesterol levels in HF DIO mice. The same extracts were also parallelly analyzed by LC-MS in both positive and negative ionization modes. Based on the pharmacological results, 22 LC-MS variables were identified to be correlated with the anti-hyperlipidemic effects using partial least square discriminant analysis (PLS-DA) and independent samples t-test. Further, under the guidance of the bioactivity-correlated LC-MS signals, 10 compounds were targetedly isolated and enriched using UPLC-DAD-MS-SPE and identified/elucidated by NMR together with MS/MS as citric acid(1), p-coumaric acid(2), hyperoside(3), myricetin(4), naringenin(5), quercetin(6), kaempferol(7), gentiopicroside(8), ursolic acid(9) and 8-epiloganic acid(10). Among these 10 compounds, 6 compounds, hyperoside(3), myricetin(4), naringenin(5), quercetin(6), kaempferol(7) and ursolic acid(9), were individually studied and reported to indeed have effects on lowering the serum lipid levels. These results demonstrated the efficiency of this strategy for drug discovery. In contrast to traditional routes to discover bioactive compounds in the plant extracts, targeted isolation and identification of bioactive compounds in the crude plant extracts using UPLC-DAD-MS-SPE/NMR based on pharmacology-guided PLS-DA of LC-MS data brings forward a new efficient dereplicated approach to natural products research for drug discovery. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Investigation of the chemomarkers correlated with flower colour in different organs of Catharanthus roseus using NMR-based metabolomics.

    Science.gov (United States)

    Pan, Qifang; Dai, Yuntao; Nuringtyas, Tri Rini; Mustafa, Natali Rianika; Schulte, Anna Elisabeth; Verpoorte, Robert; Choi, Young Hae

    2014-01-01

    Flower colour is a complex phenomenon that involves a wide range of secondary metabolites of flowers, for example phenolics and carotenoids as well as co-pigments. Biosynthesis of these metabolites, though, occurs through complicated pathways in many other plant organs. The analysis of the metabolic profile of leaves, stems and roots, for example, therefore may allow the identification of chemomarkers related to the final expression of flower colour. To investigate the metabolic profile of leaves, stems, roots and flowers of Catharanthus roseus and the possible correlation with four flower colours (orange, pink, purple and red). (1) H-NMR and multivariate data analysis were used to characterise the metabolites in the organs. The results showed that flower colour is characterised by a special pattern of metabolites such as anthocyanins, flavonoids, organic acids and sugars. The leaves, stems and roots also exhibit differences in their metabolic profiles according to the flower colour. Plants with orange flowers featured a relatively high level of kaempferol analogues in all organs except roots. Red-flowered plants showed a high level of malic acid, fumaric acid and asparagine in both flowers and leaves, and purple and pink flowering plants exhibited high levels of sucrose, glucose and 2,3-dihydroxy benzoic acid. High concentrations of quercetin analogues were detected in flowers and leaves of purple-flowered plants. There is a correlation between the metabolites specifically associated to the expression of different flower colours and the metabolite profile of other plant organs and it is therefore possible to predict the flower colours by detecting specific metabolites in leaves, stems or roots. This may have interesting application in the plant breeding industry. Copyright © 2013 John Wiley & Sons, Ltd.

  6. Biomarkers of unstable angina pectoris and yangxin decoction intervention: An exploratory metabonomics study of blood plasma.

    Science.gov (United States)

    Yu, Xiao-Hong; Sun, Jing; Wang, Yan; Zhou, Ya-Bin

    2017-05-01

    This study aimed to explore the related metabolic biomarkers and to observe the effects of Yangxin Decoction (YXD) on plasma metabolism of patients with unstable angina (UA). In total, 10 patients with UA (intervention group) and 10 healthy participants (control group) were recruited for this study from January 2009 to December 2010. Plasma samples from both groups were analyzed using liquid chromatography mass spectrometry (LC-MS). Principle component analysis (PCA) and partial least squares (PLS) were used to explore the correlations between metabolic markers in patients with UA. The LC-MS results indicated that the serum levels of 5 potential metabolic markers, namely, ceramide, glycocholic acid, allocholic acid, lithocholic acid, and leukotriene (LT) B4, were significantly higher in the intervention group than those in the control group. The results of this study demonstrated potential metabolic markers that can be used to distinguish and diagnose patients with UA.

  7. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing [181st Hospital Guangxi, Central Laboratory, Laboratory of Metabolic Diseases Research, Guangxi Province (China); Li, Liping [Guangxi Normal University, The Life Science College, Guangxi Province (China); Li, Wuxian [Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqiong Medical University, Chongqing (China); Dai, Yong [Clinical Medical Research Center, the Second Clinical Medical College of Jinan University (Shenzhen People' s Hospital), Shenzhen, Guangdong Province (China)

    2012-07-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH{sub 2}-CH = O), L5 lipids (-CH{sub 2}-C = O), and L3 lipids (-CH{sub 2}-CH{sub 2}-C = O) as well as lower levels of {beta}-glucose, {alpha}-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high

  8. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    International Nuclear Information System (INIS)

    Sui, Weiguo; Che, Wenti; Guimai, Zuo; Chen, Jiejing; Li, Liping; Li, Wuxian; Dai, Yong

    2012-01-01

    Objectives: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. Methods: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23), low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23), and high-risk patients with nephropathies of grades IV-V (N = 12). Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. Results: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-inositol, lactate, L6 lipids ( CH-CH 2 -CH = O), L5 lipids (-CH 2 -C = O), and L3 lipids (-CH 2 -CH 2 -C = O) as well as lower levels of β-glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. Conclusions: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our research

  9. A proton nuclear magnetic resonance-based metabonomics study of metabolic profiling in immunoglobulin a nephropathy

    Directory of Open Access Journals (Sweden)

    Weiguo Sui

    2012-01-01

    Full Text Available OBJECTIVES: Immunoglobulin A nephropathy is the most common cause of chronic renal failure among primary glomerulonephritis patients. The ability to diagnose immunoglobulin A nephropathy remains poor. However, renal biopsy is an inconvenient, invasive, and painful examination, and no reliable biomarkers have been developed for use in routine patient evaluations. The aims of the present study were to identify immunoglobulin A nephropathy patients, to identify useful biomarkers of immunoglobulin A nephropathy and to establish a human immunoglobulin A nephropathy metabolic profile. METHODS: Serum samples were collected from immunoglobulin A nephropathy patients who were not using immunosuppressants. A pilot study was undertaken to determine disease-specific metabolite biomarker profiles in three groups: healthy controls (N = 23, low-risk patients in whom immunoglobulin A nephropathy was confirmed as grades I-II by renal biopsy (N = 23, and high-risk patients with nephropathies of grades IV-V (N = 12. Serum samples were analyzed using proton nuclear magnetic resonance spectroscopy and by applying multivariate pattern recognition analysis for disease classification. RESULTS: Compared with the healthy controls, both the low-risk and high-risk patients had higher levels of phenylalanine, myo-Inositol, lactate, L6 lipids ( = CH-CH2-CH = O, L5 lipids (-CH2-C = O, and L3 lipids (-CH2-CH2-C = O as well as lower levels of β -glucose, α-glucose, valine, tyrosine, phosphocholine, lysine, isoleucine, glycerolphosphocholine, glycine, glutamine, glutamate, alanine, acetate, 3-hydroxybutyrate, and 1-methylhistidine. CONCLUSIONS: These metabolites investigated in this study may serve as potential biomarkers of immunoglobulin A nephropathy. Point scoring of pattern recognition analysis was able to distinguish immunoglobulin A nephropathy patients from healthy controls. However, there were no obvious differences between the low-risk and high-risk groups in our

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

    Directory of Open Access Journals (Sweden)

    Junbao Yu

    2011-09-01

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

  11. Loss of conformational entropy in protein folding calculated using realistic ensembles and its implications for NMR-based calculations

    Science.gov (United States)

    Baxa, Michael C.; Haddadian, Esmael J.; Jumper, John M.; Freed, Karl F.; Sosnick, Tobin R.

    2014-01-01

    The loss of conformational entropy is a major contribution in the thermodynamics of protein folding. However, accurate determination of the quantity has proven challenging. We calculate this loss using molecular dynamic simulations of both the native protein and a realistic denatured state ensemble. For ubiquitin, the total change in entropy is TΔSTotal = 1.4 kcal⋅mol−1 per residue at 300 K with only 20% from the loss of side-chain entropy. Our analysis exhibits mixed agreement with prior studies because of the use of more accurate ensembles and contributions from correlated motions. Buried side chains lose only a factor of 1.4 in the number of conformations available per rotamer upon folding (ΩU/ΩN). The entropy loss for helical and sheet residues differs due to the smaller motions of helical residues (TΔShelix−sheet = 0.5 kcal⋅mol−1), a property not fully reflected in the amide N-H and carbonyl C=O bond NMR order parameters. The results have implications for the thermodynamics of folding and binding, including estimates of solvent ordering and microscopic entropies obtained from NMR. PMID:25313044

  12. NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T(1)AM treatment.

    Science.gov (United States)

    Haviland, J A; Reiland, H; Butz, D E; Tonelli, M; Porter, W P; Zucchi, R; Scanlan, T S; Chiellini, G; Assadi-Porter, F M

    2013-12-01

    3-Iodothyronamine (T1 AM), an analog of thyroid hormone, is a recently discovered fast-acting endogenous metabolite. Single high-dose treatments of T1 AM have produced rapid short-term effects, including a reduction of body temperature, bradycardia, and hyperglycemia in mice. The effect of daily low doses of T1 AM (10 mg/kg) for 8 days on weight loss and metabolism in spontaneously overweight mice was monitored. The experiments were repeated twice (n = 4). Nuclear magnetic resonance (NMR) spectroscopy of plasma and real-time analysis of exhaled (13) CO2 in breath by cavity ring down spectroscopy (CRDS) were used to detect T1 AM-induced lipolysis. CRDS detected increased lipolysis in breath shortly after T1 AM administration that was associated with a significant weight loss but independent of food consumption. NMR spectroscopy revealed alterations in key metabolites in serum: valine, glycine, and 3-hydroxybutyrate, suggesting that the subchronic effects of T1 AM include both lipolysis and protein breakdown. After discontinuation of T1 AM treatment, mice regained only 1.8% of the lost weight in the following 2 weeks, indicating lasting effects of T1 AM on weight maintenance. CRDS in combination with NMR and (13) C-metabolic tracing constitute a powerful method of investigation in obesity studies for identifying in vivo biochemical pathway shifts and unanticipated debilitating side effects. Copyright © 2013 The Obesity Society.

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

    Science.gov (United States)

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

    2016-01-05

    Rheumatoid arthritis is a chronic autoimmune-based inflammatory disease that leads to progressive joint degeneration, disability, and an increased risk of cardiovascular complications, which is the main cause of mortality in this population of patients. Although several biomarkers are routinely used in the management of rheumatoid arthritis, there is a high demand for novel biomarkers to further improve the early diagnosis of rheumatoid arthritis, stratification of patients, and the prediction of a better response to a specific therapy. In this study, the metabolomics approach was used to provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy. The results indicated that twelve metabolites were important for the discrimination of healthy control and rheumatoid arthritis. Notably, valine, isoleucine, lactate, alanine, creatinine, GPC  APC and histidine relative levels were lower in rheumatoid arthritis, whereas 3-hydroxyisobutyrate, acetate, NAC, acetoacetate and acetone relative levels were higher. Simultaneously, the analysis of the concentration of metabolites in rheumatoid arthritis and 3 months after induction treatment revealed that L1, 3-hydroxyisobutyrate, lysine, L5, acetoacetate, creatine, GPC+APC, histidine and phenylalanine were elevated in RA, whereas leucine, acetate, betaine and formate were lower. Additionally, metabolomics tools were employed to discriminate between patients with different IL-17A genotypes. Metabolomics may provide relevant biomarkers to improve diagnostic accuracy, define prognosis and predict and monitor treatment efficacy in rheumatoid arthritis. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. From Metabonomics to Pharmacometabonomics: The Role of Metabolic Profiling in Personalised Medicine

    Directory of Open Access Journals (Sweden)

    Jeremy Everett

    2016-09-01

    Full Text Available Variable patient responses to drugs are a key issue for medicine and for drug discovery and development. Personalised medicine, that is the selection of medicines for subgroups of patients so as to maximise drug efficacy and minimise toxicity, is a key goal of 21st century healthcare. Currently, most personalised medicine paradigms rely on clinical judgement based on the patient’s history, and on the analysis of the patients’ genome to predict drug effects i.e. pharmacogenomics. However, variability in patient responses to drugs is dependent upon many environmental factors to which human genomics is essentially blind. A new paradigm for predicting drug responses based on individual pre-dose metabolite profiles has emerged in the past decade: pharmacometabonomics, which is defined as ‘the prediction of the outcome (for example, efficacy or toxicity of a drug or xenobiotic intervention in an individual based on a mathematical model of pre-intervention metabolite signatures’. The new pharmacometabonomics paradigm is complementary to pharmacogenomics but has the advantage of being sensitive to environmental as well as genomic factors. This review will chart the discovery and development of pharmacometabonomics, and provide examples of its current utility and possible future developments.

  15. Metabonomic Profiling of TASTPM Transgenic Alzheimer's Disease Mouse Model

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Zeping; Browne, Edward R.; Liu, Tao; Angel, Thomas E.; Ho, Paul C.; Chun Yong Chan, Eric

    2012-12-07

    Identification of molecular mechanisms underlying early stage Alzheimer’s disease (AD) is important for the development of new therapies against and diagnosis of AD. In this study, non-targeted metabotyping of TASTPM transgenic AD mice was performed. The metabolic profiles of both brain and plasma of TASTPM mice were characterized using gas chromatography-mass spectrometry and compared to those of wild type C57BL/6J mice. TASTPM mice were metabolically distinct compared to wild type mice (Q28 Y = 0.587 and 0.766 for PLS-DA models derived from brain and plasma, respectively). A number of metabolites were found to be perturbed in TASTPM mice in both brain (D11 fructose, L-valine, L-serine, L-threonine, zymosterol) and plasma (D-glucose, D12 galactose, linoleic acid, arachidonic acid, palmitic acid and D-gluconic acid). In addition, enzyme immunoassay confirmed that selected endogenous steroids were significantly perturbed in brain (androstenedione and 17-OH-progesterone) and plasma (cortisol and testosterone) of TASTPM mice. Ingenuity pathway analysis revealed that perturbations related to amino acid metabolism (brain), steroid biosynthesis (brain), linoleic acid metabolism (plasma) and energy metabolism (plasma) accounted for the differentiation of TASTPM and wild-type

  16. Metabonomics study on Polygonum multiflorum induced liver toxicity in rats by GC-MS.

    Science.gov (United States)

    Zhang, Yuan; Wang, Nannan; Zhang, Meiling; Diao, Tingting; Tang, Jingyue; Dai, Mingzhu; Chen, Suhong; Lin, Guanyang

    2015-01-01

    Polygonum multiflorum, a traditional Chinese medicinal herb, is widely used in liver and liver nourishing. Recent years, drug regulatory departments reported that Polygonum multiflorum caused serious adverse reaction in clinic, especially liver injury. In this study, we detected the changes in rat serum and liver tissue metabolites through gas chromatography-mass spectrometry (GC-MS). Mass spectrometry, partial least squares-discriminate analysis (PLS-DA) and other diversified techniques were used to analyze the differences among their metabolites. Compared to the control group, the serum concentrations of L-threonine and serine in water extraction groups increased. The serum concentrations of 9,12-octadecadienoic acid, hexadecanoic acid, oleic acid, D-glucose and octadecanoic acid in alcohol extraction groups increased, while lactic acid decreased to a great extent. For liver tissue, compared to the control group, the concentrations of myo-inositol, oleic acid and cholesterol in water extraction groups increased, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased to a great extent. The concentrations of myo-inositol, phosphoric acid, uridine, oleic acid, cholesterol and butanoic acid in alcohol extraction groups increased to a great extent, while those of hexadecanoic acid, octadecanoic acid, ribitol and butanedioic acid decreased. The results indicate that Polygonum multiflorum induces the metabolic disorders of energy metabolism, amino acid and lipid metabolism. What's more, liver injury of alcohol extraction group was more serious than group of water extraction.

  17. NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

    Science.gov (United States)

    Liu, Haiyan; Tayyari, Fariba; Edison, Arthur S; Su, Zhihua; Gu, Liwei

    2016-08-01

    A (1)H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using (1)H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D (1)H-(13)C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and α-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, α-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Serum metabonomics of rats irradiated by low-dose γ-rays

    Directory of Open Access Journals (Sweden)

    Ying HE

    2014-08-01

    Full Text Available Objective To explore the effect of low-dose γ-rays on the metabolites in rat serum. Methods Sixteen healthy male SD rats were randomly divided into control group and irradiated group (n=8. The rats in irradiated group were irradiated by 60Co γ-rays with a dose rate of 72mGy/h for 7 days (1 hour per day. At the 7th day after irradiation, blood samples were taken from abdominal aorta to obtain the serum. The metabolic fingerprints of serum were obtained from the two groups of rats, and 1H nuclear magnetic resonance (NMR spectroscopy, principal component analysis (PCA and orthogonal signal correction-partial least squares (OSC-PLS method were used for pattern recognition, and the difference in metabolite profile between two groups was identified by SIMCA-P software. Results The rat serum 1H NMR spectra revealed a significant difference between control group and irradiated group, the OSC-PLS plots of the serum samples presented marked clustering between two groups. Compared with the control group, the content of lipid, glucose, creatine, glycine/glucose, high density lipoprotein, low density lipoprotein, very low density lipoprotein/low density lipoprotein and unsaturated fatty acid increased, while the content of lactic acid, threonine/lipid, alanine, N-acetyl glycoprotein 1, N-acetyl glycoprotein 2, saturated fatty acid and phosphatidyl choline decreased in irradiated group. Conclusion Irradiation with low-dose γ-ray could induce changes in metabolites in rat serum, concerning mainly immune function, energy metabolism, carbohydrate metabolism and lipid metabolism. DOI: 10.11855/j.issn.0577-7402.2014.07.02

  19. Longitudinal Omics Modelling and Integration in Clinical Metabonomics Research: challenges in childhood metabolic health research

    Directory of Open Access Journals (Sweden)

    Peter eSperisen

    2015-08-01

    Full Text Available Systems biology is an important approach for deciphering the complex processes in health maintenance and the etiology of metabolic diseases. Such integrative methodologies will help better understand the molecular mechanisms involved in growth and development throughout childhood, and consequently will result in new insights about metabolic and nutritional requirements of infants, children and adults. To achieve this, a better understanding of the physiological processes at anthropometric, cellular and molecular level for any given individual is needed. In this respect, novel omics technologies in combination with sophisticated data modelling techniques are key. Due to the highly complex network of influential factors determining individual trajectories, it becomes imperative to develop proper tools and solutions that will comprehensively model biological information related to growth and maturation of our body functions. The aim of this review and perspective is to evaluate, succinctly, promising data analysis approaches to enable data integration for clinical research, with an emphasis on the longitudinal component. Approaches based on empirical and mechanistic modelling of omics data are essential to leverage findings from high dimensional omics datasets and enable biological interpretation and clinical translation. On the one hand, empirical methods, which provide quantitative descriptions of patterns in the data, are mostly used for exploring and mining datasets. On the other hand, mechanistic models are based on an understanding of the behavior of a system’s components and condense information about the known functions, allowing robust and reliable analyses to be performed by bioinformatics pipelines and similar tools. Herein, we will illustrate current examples, challenges and perspectives in the applications of empirical and mechanistic modelling in the context of childhood metabolic health research.

  20. Longitudinal omics modeling and integration in clinical metabonomics research: challenges in childhood metabolic health research

    Science.gov (United States)

    Sperisen, Peter; Cominetti, Ornella; Martin, François-Pierre J.

    2015-01-01

    Systems biology is an important approach for deciphering the complex processes in health maintenance and the etiology of metabolic diseases. Such integrative methodologies will help better understand the molecular mechanisms involved in growth and development throughout childhood, and consequently will result in new insights about metabolic and nutritional requirements of infants, children and adults. To achieve this, a better understanding of the physiological processes at anthropometric, cellular and molecular level for any given individual is needed. In this respect, novel omics technologies in combination with sophisticated data modeling techniques are key. Due to the highly complex network of influential factors determining individual trajectories, it becomes imperative to develop proper tools and solutions that will comprehensively model biological information related to growth and maturation of our body functions. The aim of this review and perspective is to evaluate, succinctly, promising data analysis approaches to enable data integration for clinical research, with an emphasis on the longitudinal component. Approaches based on empirical and mechanistic modeling of omics data are essential to leverage findings from high dimensional omics datasets and enable biological interpretation and clinical translation. On the one hand, empirical methods, which provide quantitative descriptions of patterns in the data, are mostly used for exploring and mining datasets. On the other hand, mechanistic models are based on an understanding of the behavior of a system's components and condense information about the known functions, allowing robust and reliable analyses to be performed by bioinformatics pipelines and similar tools. Herein, we will illustrate current examples, challenges and perspectives in the applications of empirical and mechanistic modeling in the context of childhood metabolic health research. PMID:26301225

  1. Fast Identification of Radical Scavengers from Securigera varia by Combining 13C-NMR-Based Dereplication to Bioactivity-Guided Fractionation.

    Science.gov (United States)

    Sientzoff, Pacôme; Hubert, Jane; Janin, Coralie; Voutquenne-Nazabadioko, Laurence; Renault, Jean-Hugues; Nuzillard, Jean-Marc; Harakat, Dominique; Magid, Abdulmagid Alabdul

    2015-08-14

    Securigera varia (Fabaceae) is a common herbaceous perennial plant widely growing in Europe and Asia and purposely established for erosion control, roadside planting, and soil rehabilitation. The aim of this study was to determine the radical scavenging activity of a crude methanol extract of S. varia aerial parts by using the free radical DPPH (1,1-diphenyl-2-picrylhydrazyl) and to rapidly identify the compounds involved in this activity. The crude extract was initially separated in five fractions on Diaion HP20 resin and the most active part was fractionated by Centrifugal Partition Extraction (CPE). Known compounds were directly identified by a (13)C-NMR-based dereplication method. Semi-preparative high performance liquid chromatography purification experiments were further performed to identify unknown or minor active compounds. As a result, one new (13) and twelve known flavonoid glycosides together with three nitropropanoylglucopyranoses were isolated, including astragalin (1), kaempferol-3-O-(6-O-acetyl)-β-D-glucopyranoside (2), kaempferol-3,4'-di-O-β-D-glucopyranoside (3), trifolin (4), isoquercitrin (5), hyperoside (6), isovitexin (7), isoorientin (8), isovitexin 4'-O-β-D-glucopyranoside (9), apigenin 7-O-β-D-glucuronopyranoside (10), luteolin 7-O-β-D-glucuronopyranoside (11), apigenin 7-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucuronopyranoside (12), apigenin 7-O-β-D-glucopyranosyl-(1 → 2)-β-D-glucuronopyranoside (13), 6-O-(3-nitropropanoyl)-β-D-glucopyranoside (14), coronillin (16) and coronarian (15). 120 mg of the most active compound isoorientin against the free radical DPPH was recovered by CPE with an HPLC purity of 99%.

  2. Fast Identification of Radical Scavengers from Securigera varia by Combining 13C-NMR-Based Dereplication to Bioactivity-Guided Fractionation

    Directory of Open Access Journals (Sweden)

    Pacôme Sientzoff

    2015-08-01

    Full Text Available Securigera varia (Fabaceae is a common herbaceous perennial plant widely growing in Europe and Asia and purposely established for erosion control, roadside planting, and soil rehabilitation. The aim of this study was to determine the radical scavenging activity of a crude methanol extract of S. varia aerial parts by using the free radical DPPH (1,1-diphenyl-2-picrylhydrazyl and to rapidly identify the compounds involved in this activity. The crude extract was initially separated in five fractions on Diaion HP20 resin and the most active part was fractionated by Centrifugal Partition Extraction (CPE. Known compounds were directly identified by a 13C-NMR-based dereplication method. Semi-preparative high performance liquid chromatography purification experiments were further performed to identify unknown or minor active compounds. As a result, one new (13 and twelve known flavonoid glycosides together with three nitropropanoylglucopyranoses were isolated, including astragalin (1, kaempferol-3-O-(6-O-acetyl-β-D-glucopyranoside (2, kaempferol-3,4′-di-O-β-D-glucopyranoside (3, trifolin (4, isoquercitrin (5, hyperoside (6, isovitexin (7, isoorientin (8, isovitexin 4′-O-β-D-glucopyranoside (9, apigenin 7-O-β-D-glucuronopyranoside (10, luteolin 7-O-β-D-glucuronopyranoside (11, apigenin 7-O-α-L-rhamnopyranosyl-(1→2-β-D-glucuronopyranoside (12, apigenin 7-O-β-D-glucopyranosyl-(1→2-β-D-glucuronopyranoside (13, 6-O-(3-nitropropanoyl-β-D-glucopyranoside (14, coronillin (16 and coronarian (15. 120 mg of the most active compound isoorientin against the free radical DPPH was recovered by CPE with an HPLC purity of 99%.

  3. Divergent Urinary Metabolic Phenotypes between Major Depressive Disorder and Bipolar Disorder Identified by a Combined GC-MS and NMR Spectroscopic Metabonomic Approach.

    Science.gov (United States)

    Chen, Jian-Jun; Zhou, Chan-Juan; Liu, Zhao; Fu, Yu-Ying; Zheng, Peng; Yang, De-Yu; Li, Qi; Mu, Jun; Wei, You-Dong; Zhou, Jing-Jing; Huang, Hua; Xie, Peng

    2015-08-07

    Bipolar disorder (BD) is a complex debilitating mental disorder that is often misdiagnosed as major depressive disorder (MDD). Therefore, a large percentage of BD subjects are incorrectly treated with antidepressants in clinical practice. To address this challenge, objective laboratory-based tests are needed to discriminate BD from MDD patients. Here, a combined gas chromatography-mass spectrometry (GC-MS)-based and nuclear magnetic resonance (NMR) spectroscopic-based metabonomic approach was performed to profile urine samples from 76 MDD and 43 BD subjects (training set) to identify the differential metabolites. Samples from 126 healthy controls were included as metabolic controls. A candidate biomarker panel was identified by further analyzing these differential metabolites. A testing set of, 50 MDD and 28 BD subjects was then used to independently validate the diagnostic efficacy of the identified panel using an area under the receiver operating characteristic curve (AUC). A total of 20 differential metabolites responsible for the discrimination between MDD and BD subjects were identified. A panel consisting of six candidate urinary metabolite biomarkers (propionate, formate, (R*,S*)2,3-dihydroxybutanoic acid, 2,4-dihydroxypyrimidine, phenylalanine, and β-alanine) was identified. This panel could distinguish BD from MDD subjects with an AUC of 0.913 and 0.896 in the training and testing sets, respectively. These results reveal divergent urinary metabolic phenotypes between MDD and BD. The identified urinary biomarkers can aid in the future development of an objective laboratory-based diagnostic test for distinguishing BD from MDD patients.

  4. {sup 1}H NMR-based metabolomics reveals sub-lethal toxicity of a mixture of diabetic and lipid-regulating pharmaceuticals on amphibian larvae

    Energy Technology Data Exchange (ETDEWEB)

    Melvin, Steven D., E-mail: s.melvin@griffith.edu.au [Australian Rivers Institute, Griffith University, Southport, QLD 4222 (Australia); Habener, Leesa J. [Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia); Leusch, Frederic D.L. [Australian Rivers Institute, Griffith University, Southport, QLD 4222 (Australia); Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia); Carroll, Anthony R. [Griffith School of Environment, Griffith University, Southport, QLD 4222 (Australia)

    2017-03-15

    Highlights: • Pharmaceutical pollutants are a concern for eliciting adverse effects in wildlife. • Diabetes and lipid regulating drugs are widely used and poorly removed from sewage. • We explored the toxicity of a mixture of metformin, atorvastatin and bezafibrate on tadpoles. • Exposure caused increased growth and development but no effects on lipids or cholesterol. • {sup 1}H NMR-based metabolomics reveal increased lactic acid and BCAAs in exposed animals. - Abstract: Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment. In this study, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to a mixture of the drugs metformin, atorvastatin and bezafibrate at 0.5, 5, 50 and 500 μg/L to explore possible effects on growth and development, energy reserves (triglycerides and cholesterol), and profiles of small polar metabolites extracted from hepatic tissues. It was hypothesised that exposure would result in a general reduction in energy reserves, and that this would subsequently correspond with reduced growth and development. Responses differed from expected outcomes based on the known mechanisms of these compounds in humans, with no changes to hepatic triglycerides or cholesterol and a general increase in mass and condition with increasing exposure concentration. Deviation from the

  5. 1H NMR-based metabolomics reveals sub-lethal toxicity of a mixture of diabetic and lipid-regulating pharmaceuticals on amphibian larvae

    International Nuclear Information System (INIS)

    Melvin, Steven D.; Habener, Leesa J.; Leusch, Frederic D.L.; Carroll, Anthony R.

    2017-01-01

    Highlights: • Pharmaceutical pollutants are a concern for eliciting adverse effects in wildlife. • Diabetes and lipid regulating drugs are widely used and poorly removed from sewage. • We explored the toxicity of a mixture of metformin, atorvastatin and bezafibrate on tadpoles. • Exposure caused increased growth and development but no effects on lipids or cholesterol. • 1 H NMR-based metabolomics reveal increased lactic acid and BCAAs in exposed animals. - Abstract: Pharmaceuticals are widely used for the treatment of various physical and psychological ailments. Due to incomplete removal during sewage treatment many pharmaceuticals are frequently detected in aquatic waterways at trace concentrations. The diversity of pharmaceutical contaminants and potential for complex mixtures to occur makes it very difficult to predict the toxicity of these compounds on wildlife, and robust methods are therefore needed to explore sub-lethal effects. Metabolic syndrome is one of the most widespread health concerns currently facing the human population, and various drugs, including anti-diabetic medications and lipid- and cholesterol-lowering fibrates and statins, are widely prescribed as treatment. In this study, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to a mixture of the drugs metformin, atorvastatin and bezafibrate at 0.5, 5, 50 and 500 μg/L to explore possible effects on growth and development, energy reserves (triglycerides and cholesterol), and profiles of small polar metabolites extracted from hepatic tissues. It was hypothesised that exposure would result in a general reduction in energy reserves, and that this would subsequently correspond with reduced growth and development. Responses differed from expected outcomes based on the known mechanisms of these compounds in humans, with no changes to hepatic triglycerides or cholesterol and a general increase in mass and condition with increasing exposure concentration. Deviation from the

  6. Expression and purification of 15N- and 13C-isotope labeled 40-residue human Alzheimer’s β-amyloid peptide for NMR-based structural analysis

    OpenAIRE

    Long, Fei; Cho, Wonhwa; Ishii, Yoshitaka

    2011-01-01

    Amyloid fibrils of Alzheimer’s β-amyloid peptide (Aβ) are a primary component of amyloid plaques, a hallmark of Alzheimer’s disease (AD). Enormous attention has been given to the structural features and functions of Aβ in amyloid fibrils and other type of aggregates in associated with development of AD. This report describes an efficient protocol to express and purify high-quality 40-residue Aβ(1–40), the most abundant Aβ in brains, for structural studies by NMR spectroscopy. Over-expression ...

  7. Mechanisms of metabonomic for a gateway drug: nicotine priming enhances behavioral response to cocaine with modification in energy metabolism and neurotransmitter level.

    Directory of Open Access Journals (Sweden)

    Hongyu Li

    Full Text Available Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. (1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism.

  8. Mechanisms of Metabonomic for a Gateway Drug: Nicotine Priming Enhances Behavioral Response to Cocaine with Modification in Energy Metabolism and Neurotransmitter Level

    Science.gov (United States)

    Li, Hongyu; Bu, Qian; Chen, Bo; Shao, Xue; Hu, Zhengtao; Deng, Pengchi; Lv, Lei; Deng, Yi; Zhu, Ruiming; Li, Yan; Zhang, Baolai; Hou, Jing; Du, Changman; Zhao, Qian; Fu, Dengqi; Zhao, Yinglan; Cen, Xiaobo

    2014-01-01

    Nicotine, one of the most commonly used drugs, has become a major concern because tobacco serves as a gateway drug and is linked to illicit drug abuse, such as cocaine and marijuana. However, previous studies mainly focused on certain genes or neurotransmitters which have already been known to participate in drug addiction, lacking endogenous metabolic profiling in a global view. To further explore the mechanism by which nicotine modifies the response to cocaine, we developed two conditioned place preference (CPP) models in mice. In threshold dose model, mice were pretreated with nicotine, followed by cocaine treatment at the dose of 2 mg/kg, a threshold dose of cocaine to induce CPP in mice. In high-dose model, mice were only treated with 20 mg/kg cocaine, which induced a significant CPP. 1H nuclear magnetic resonance based on metabonomics was used to investigate metabolic profiles of the nucleus accumbens (NAc) and striatum. We found that nicotine pretreatment dramatically increased CPP induced by 2 mg/kg cocaine, which was similar to 20 mg/kg cocaine-induced CPP. Interestingly, metabolic profiles showed considerable overlap between these two models. These overlapped metabolites mainly included neurotransmitters as well as the molecules participating in energy homeostasis and cellular metabolism. Our results show that the reinforcing effect of nicotine on behavioral response to cocaine may attribute to the modification of some specific metabolites in NAc and striatum, thus creating a favorable metabolic environment for enhancing conditioned rewarding effect of cocaine. Our findings provide an insight into the effect of cigarette smoking on cocaine dependence and the underlying mechanism. PMID:24489831

  9. Application of ultraperformance liquid chromatography/mass spectrometry-based metabonomic techniques to analyze the joint toxic action of long-term low-level exposure to a mixture of organophosphate pesticides on rat urine profile.

    Science.gov (United States)

    Du, Longfei; Wang, Hong; Xu, Wei; Zeng, Yan; Hou, Yurong; Zhang, Yuqiu; Zhao, Xiujuan; Sun, Changhao

    2013-07-01

    In previously published articles, we evaluated the toxicity of four organophosphate (OP) pesticides (dichlorvos, dimethoate, acephate, and phorate) to rats using metabonomic technology at their corresponding no observed adverse effect level (NOAEL). Results show that a single pesticide elicits no toxic response. This study aimed to determine whether chronic exposure to a mixture of the above four pesticides (at their corresponding NOAEL) can lead to joint toxic action in rats using the same technology. Pesticides were administered daily to rats through drinking water for 24 weeks. The above mixture of the four pesticides showed joint toxic action at the NOAEL of each pesticide. The metabonomic profiles of rats urine were analyzed by ultraperformance liquid chromatography/mass spectrometry. The 16 metabolites statistically significantly changed in all treated groups compared with the control group. Dimethylphosphate and dimethyldithiophosphate exclusively detected in all treated groups can be used as early, sensitive biomarkers for exposure to a mixture of the OP pesticides. Moreover, exposure to the OP pesticides resulted in increased 7-methylguanine, ribothymidine, cholic acid, 4-pyridoxic acid, kynurenine, and indoxyl sulfate levels, as well as decreased hippuric acid, creatinine, uric acid, gentisic acid, C18-dihydrosphingosine, phytosphingosine, suberic acid, and citric acid. The results indicated that a mixture of OP pesticides induced DNA damage and oxidative stress, disturbed the metabolism of lipids, and interfered with the tricarboxylic acid cycle. Ensuring food safety requires not only the toxicology test data of each pesticide for the calculation of the acceptable daily intake but also the joint toxic action.

  10. NMR-based identification of the phenolic profile of fruits of Lycium barbarum (goji berries). Isolation and structural determination of a novel N-feruloyl tyramine dimer as the most abundant antioxidant polyphenol of goji berries.

    Science.gov (United States)

    Forino, Martino; Tartaglione, Luciana; Dell'Aversano, Carmela; Ciminiello, Patrizia

    2016-03-01

    Biological properties of fruits of Lycium barbarum (goji berries) have been ascribed to their high content of nutrients and phenolics. Comprehensive studies aimed at unambiguously identifying the phenolic components in goji berries are still lacking. In this paper, we report on the isolation and NMR-based identification of the major phenolics in commercially available goji berries. Together with already known phenolics, including caffeic acid, p-coumaric acid, rutin, scopoletin, N-trans-feruloyl tyramine, and N-cis-feruloyl tyramine, an unreported N-feruloyl tyramine dimer was characterized as the most abundant polyphenol isolated from the berries. Usually divalent molecules show enhanced biological activities than their corresponding monomers. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. A novel NMR-based assay to measure circulating concentrations of branched-chain amino acids: Elevation in subjects with type 2 diabetes mellitus and association with carotid intima media thickness.

    Science.gov (United States)

    Wolak-Dinsmore, Justyna; Gruppen, Eke G; Shalaurova, Irina; Matyus, Steven P; Grant, Russell P; Gegen, Ray; Bakker, Stephan J L; Otvos, James D; Connelly, Margery A; Dullaart, Robin P F

    2018-04-01

    Plasma branched-chain amino acid (BCAA) levels, measured on nuclear magnetic resonance (NMR) metabolomics research platforms or by mass spectrometry, have been shown to be associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We developed a new test for quantification of BCAA on a clinical NMR analyzer and used this test to determine the clinical correlates of BCAA in 2 independent cohorts. The performance of the NMR-based BCAA assay was evaluated. A method comparison study was performed with mass spectrometry (LC-MS/MS). Plasma BCAA were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1209; 376 T2DM subjects) and in a Groningen cohort (n = 123; 67 T2DM subjects). In addition, carotid intima media thickness (cIMT) was measured successfully in 119 subjects from the Groningen cohort. NMR-based BCAA assay results were linear over a range of concentrations. Coefficients of variation for inter- and intra-assay precision ranged from 1.8-6.0, 1.7-5.4, 4.4-9.1, and 8.8-21.3%, for total BCAA, valine, leucine, and isoleucine, respectively. BCAA quantified from the same samples using NMR and LC-MS/MS were highly correlated (R 2  = 0.97, 0.95 and 0.90 for valine, leucine and isoleucine). In both cohorts total and individual BCAA were elevated in T2DM (P = 0.01 to ≤0.001). Moreover, cIMT was associated with BCAA independent of age, sex, T2DM and metabolic syndrome (MetS) categorization or alternatively of individual MetS components. BCAA levels, measured by NMR in the clinical laboratory, are elevated in T2DM and may be associated with cIMT, a proxy of subclinical atherosclerosis. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  12. “Omics” Prospective Monitoring of Bariatric Surgery: Roux-En-Y Gastric Bypass Outcomes Using Mixed-Meal Tolerance Test and Time-Resolved 1H NMR-Based Metabolomics

    Science.gov (United States)

    Lopes, Thiago I.B.; Geloneze, Bruno; Pareja, José C.; Calixto, Antônio R.; Ferreira, Márcia M.C.

    2016-01-01

    Abstract Roux-en-Y gastric bypass (RYGB) surgery goes beyond weight loss to induce early beneficial hormonal changes that favor glycemic control. In this prospective study, ten obese subjects diagnosed with type 2 diabetes underwent bariatric surgery. Mixed-meal tolerance test was performed before and 12 months after RYGB, and the outcomes were investigated by a time-resolved hydrogen nuclear magnetic resonance (1H NMR)-based metabolomics. To the best of our knowledge, no previous omics-driven study has used time-resolved 1H NMR-based metabolomics to investigate bariatric surgery outcomes. Our results presented here show a significant decrease in glucose levels after bariatric surgery (from 159.80 ± 61.43 to 100.00 ± 22.94 mg/dL), demonstrating type 2 diabetes remission (p < 0.05). The metabolic profile indicated lower levels of lactate, alanine, and branched chain amino acids for the operated subject at fasting state after the surgery. However, soon after food ingestion, the levels of these metabolites increased faster in operated than in nonoperated subjects. The lipoprotein profile achieved before and after RYGB at fasting was also significantly different, but converging 180 min after food ingestion. For example, the very low-density lipoprotein, low-density lipoprotein, N-acetyl-glycoproteins, and unsaturated lipid levels decreased after RYGB, while phosphatidylcholine and high-density lipoprotein increased. This study provides important insights on RYGB surgery and attendant type 2 diabetes outcomes using an “omics” systems science approach. Further research on metabolomic correlates of RYGB surgery in larger study samples is called for. PMID:27428253

  13. [Mass spectrometry technology and its application in analysis of biological samples].

    Science.gov (United States)

    Zhao, Long-Shan; Li, Qing; Guo, Chao-Wei; Chen, Xiao-Hui; Bi, Kai-Shun

    2012-02-01

    With the excellent merits of wide analytical range, high sensitivity, small sample size, fast analysis speed, good repeatability, simple operation, low mobile phase consumption, as well as its capability of simultaneous isolation and identification, etc, mass spectrometry techniques have become widely used in the area of environmental science, energy chemical industry, biological medicine, and so on. This article reviews the application of mass spectrometry technology in biological sample analysis in the latest three years with the focus on the new applications in pharmacokinetics and bioequivalence, toxicokinetics, pharmacokinetic-pharmacodynamic, population pharmacokinetics, identification and fragmentation pathways of drugs and their metabolites and metabonomics to provide references for further study of biological sample analysis.

  14. Metabonomics research of diabetic nephropathy and type 2 diabetes mellitus based on UPLC-oaTOF-MS system

    International Nuclear Information System (INIS)

    Zhang Jie; Yan Lijuan; Chen Wengui; Lin Lin; Song Xiuyu; Yan Xiaomei; Hang Wei; Huang Benli

    2009-01-01

    Ultra performance liquid chromatography (UPLC) coupled with orthogonal acceleration time-of-flight (oaTOF) mass spectrometry has showed great potential in diabetes research. In this paper, a UPLC-oaTOF-MS system was employed to distinguish the global serum profiles of 8 diabetic nephropathy (DN) patients, 33 type 2 diabetes mellitus (T2DM) patients and 25 healthy volunteers, and tried to find potential biomarkers. The UPLC system produced information-rich chromatograms with typical measured peak widths of 4 s, generating peak capacities of 225 in 15 min. Furthermore, principal component analysis (PCA) was used for group differentiation and marker selection. As shown in the scores plot, the distinct clustering between the patients and controls was observed, and DN and T2DM patients were also separated into two individual groups. Several compounds were tentatively identified based on accurate mass, isotopic pattern and MS/MS information. In addition, significant changes in the serum level of leucine, dihydrosphingosine and phytoshpingosine were noted, indicating the perturbations of amino acid metabolism and phospholipid metabolism in diabetic diseases, which having implications in clinical diagnosis and treatment.

  15. Metabonomics research of diabetic nephropathy and type 2 diabetes mellitus based on UPLC-oaTOF-MS system

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jie, E-mail: jiezhang@dicp.ac.cn [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China); Yan Lijuan [XiaMen Entry-Exit Inspection and Quarantine Bureau, 361012 Xiamen (China); Chen Wengui [First Hospital of Xiamen, 361003 Xiamen (China); Lin Lin [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China); Song Xiuyu [First Hospital of Xiamen, 361003 Xiamen (China); Yan Xiaomei [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China); Hang Wei, E-mail: weihang@xmu.edu.cn [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China); Huang Benli [Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, 361005 Xiamen (China)

    2009-09-14

    Ultra performance liquid chromatography (UPLC) coupled with orthogonal acceleration time-of-flight (oaTOF) mass spectrometry has showed great potential in diabetes research. In this paper, a UPLC-oaTOF-MS system was employed to distinguish the global serum profiles of 8 diabetic nephropathy (DN) patients, 33 type 2 diabetes mellitus (T2DM) patients and 25 healthy volunteers, and tried to find potential biomarkers. The UPLC system produced information-rich chromatograms with typical measured peak widths of 4 s, generating peak capacities of 225 in 15 min. Furthermore, principal component analysis (PCA) was used for group differentiation and marker selection. As shown in the scores plot, the distinct clustering between the patients and controls was observed, and DN and T2DM patients were also separated into two individual groups. Several compounds were tentatively identified based on accurate mass, isotopic pattern and MS/MS information. In addition, significant changes in the serum level of leucine, dihydrosphingosine and phytoshpingosine were noted, indicating the perturbations of amino acid metabolism and phospholipid metabolism in diabetic diseases, which having implications in clinical diagnosis and treatment.

  16. Metabonomic Profiling Reveals Cancer Chemopreventive Effects of American Ginseng on Colon Carcinogenesis in Apc(Min/+) Mice.

    Science.gov (United States)

    Xie, Guoxiang; Wang, Chong-Zhi; Yu, Chunhao; Qiu, Yunping; Wen, Xiao-Dong; Zhang, Chun-Feng; Yuan, Chun-Su; Jia, Wei

    2015-08-07

    American ginseng (Panax quinquefolius L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered Apc(Min/+) mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the Apc(Min/+) mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids, and carbohydrates were observed in Apc(Min/+) mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates, and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the Apc(Min/+) induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms.

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

    Science.gov (United States)

    Tian, Jun-Sheng; Xia, Xiao-Tao; Wu, Yan-Fei; Zhao, Lei; Xiang, Huan; Du, Guan-Hua; Zhang, Xiang; Qin, Xue-Mei

    2016-09-21

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

  18. Metabolomic analysis of alterations in lipid oxidation, carbohydrate and amino acid metabolism in dairy goats caused by exposure to Aflotoxin B1.

    Science.gov (United States)

    Cheng, Jianbo; Huang, Shuai; Fan, Caiyun; Zheng, Nan; Zhang, Yangdong; Li, Songli; Wang, Jiaqi

    2017-11-01

    The purposes of this study were to investigate the systemic and characteristic metabolites in the serum of dairy goats induced by aflatoxin B1 (AFB1) exposure and to further understand the endogenous metabolic alterations induced by it. A nuclear magnetic resonance (NMR)-based metabonomic approach was used to analyse the metabolic alterations in dairy goats that were induced by low doses of AFB1 (50 µg/kg DM). We found that AFB1 exposure caused significant elevations of glucose, citrate, acetate, acetoacetate, betaine, and glycine yet caused reductions of lactate, ketone bodies (acetate, β-hydroxybutyrate), amino acids (citrulline, leucine/isoleucine, valine, creatine) and cell membrane structures (choline, lipoprotein, N-acetyl glycoproteins) in the serum. These data indicated that AFB1 caused endogenous metabolic changes in various metabolic pathways, including cell membrane-associated metabolism, the tricarboxylic acid cycle, glycolysis, lipids, and amino acid metabolism. These findings provide both a comprehensive insight into the metabolic aspects of AFB1-induced adverse effects on dairy goats and a method for monitoring dairy animals exposed to low doses of AFB1.

  19. Application of {sup 1}H-NMR-based metabolomics for detecting injury induced by long-term microwave exposure in Wistar rats' urine

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Li-Feng; Peng, Rui-Yun; Wang, Shui-Ming; Gao, Ya-Bing; Dong, Ji; Zhao, Li; Li, Xiang; Zuo, Hong-Yan; Wang, Chang-Zhen [Beijing Institute of Radiation Medicine, Laboratory of Pathology, Beijing (China); Hu, Xiang-Jun [Beijing Institute of Radiation Medicine, Beijing (China); Gao, Rong-Lian [Beijing Institute of Radiation Medicine, Laser Medicine, Beijing (China); Su, Zhen-Tao [Beijing Institute of Radiation Medicine, Radiation Protection, Beijing (China); Feng, Xin-Xing [Chinese Academy of Medical Sciences, Endocrine and Cardiovascular Center, Fuwai Hospital and Cardiovascular Institute, Beijing (China)

    2012-07-15

    There has been growing public concern regarding exposure to microwave fields as a potential human health hazard. This study aimed to identify sensitive biochemical indexes for the detection of injury induced by microwave exposure. Male Wistar rats were exposed to microwaves for 6 min per day, 5 days per week over a period of 1 month at an average power density of 5 mW/cm{sup 2} (specific absorption rate of 2.1 W/kg). Urine specimens were collected over 24 h in metabolic cages at 7 days, 21 days, 2 months, and 6 months after exposure. {sup 1}H NMR spectroscopy data were analyzed using multivariate statistical techniques. Urine metabolic profiles of rats after long-term microwave exposure were significantly differentiated from those of sham-treated controls using principal component analysis or partial least squares discriminant analysis. Significant differences in low molecular weight metabolites (acetate, succinate, citrate, ketoglutarate, glucose, taurine, phenylalanine, tyrosine, and hippurate) were identified in the 5 mW/cm{sup 2} microwave exposure group compared with the sham-treated controls at 7 days, 21 days, and 2 months. Metabolites returned to normal levels by 6 months after exposure. These data indicated that these metabolites were related to the perturbations of energy metabolism particularly in the tricarboxylic acid cycle, and the metabolism of amino acids, monoamines, and choline in urine represent potential indexes for the detection of injury induced by long-term microwave exposure. (orig.)

  20. 1H NMR-Based Metabolomics Study of the Toxicological Effects in Rats Induced by “Renqing Mangjue” Pill, a Traditional Tibetan Medicine

    Directory of Open Access Journals (Sweden)

    Can Xu

    2017-09-01

    Full Text Available “RenqingMangjue” pill (RMP, as an effective prescription of Traditional Tibetan Medicine (TTM, has been widely used in treating digestive diseases and ulcerative colitis for over a thousand years. In certain classical Tibetan Medicine, heavy metal may add as an active ingredient, but it may cause contamination unintentionally in some cases. Therefore, the toxicity and adverse effects of TTM became to draw public attention. In this study, 48 male Wistar rats were orally administrated with different dosages of RMP once a day for 15 consecutive days, then half of the rats were euthanized on the 15th day and the remaining were euthanized on the 30th day. Plasma, kidney and liver samples were acquired to 1H NMR metabolomics analysis. Histopathology and ICP-MS were applied to support the metabolomics findings. The metabolic signature of plasma from RMP-administrated rats exhibited increasing levels of glucose, betaine, and creatine, together with decreasing levels of lipids, 3-hydroxybutate, pyruvate, citrate, valine, leucine, isoleucine, glutamate, and glutamine. The metabolomics analysis results of liver showed that after RMP administration, the concentrations of valine, leucine, proline, tyrosine, and tryptophan elevated, while glucose, sarcosine and 3-hydroxybutyrate decreased. The levels of metabolites in kidney, such as, leucine, valine, isoleucine and tyrosine, were increased, while taurine, glutamate, and glutamine decreased. The study provides several potential biomarkers for the toxicity mechanism research of RMP and shows that RMP may cause injury in kidney and liver and disturbance of several pathways, such as energy metabolism, oxidative stress, glucose and amino acids metabolism.

  1. GFT projection NMR based resonance assignment of membrane proteins: application to subunit C of E. coli F(1)F (0) ATP synthase in LPPG micelles.

    Science.gov (United States)

    Zhang, Qi; Atreya, Hanudatta S; Kamen, Douglas E; Girvin, Mark E; Szyperski, Thomas

    2008-03-01

    G-matrix FT projection NMR spectroscopy was employed for resonance assignment of the 79-residue subunit c of the Escherichia coli F(1)F(0) ATP synthase embedded in micelles formed by lyso palmitoyl phosphatidyl glycerol (LPPG). Five GFT NMR experiments, that is, (3,2)D HNNCO, L-(4,3)D HNNC (alphabeta) C (alpha), L-(4,3)D HNN(CO)C (alphabeta) C (alpha), (4,2)D HACA(CO)NHN and (4,3)D HCCH, were acquired along with simultaneous 3D (15)N, (13)C(aliphatic), (13)C(aromatic)-resolved [(1)H,(1)H]-NOESY with a total measurement time of approximately 43 h. Data analysis resulted in sequence specific assignments for all routinely measured backbone and (13)C(beta) shifts, and for 97% of the side chain shifts. Moreover, the use of two G(2)FT NMR experiments, that is, (5,3)D HN{N,CO}{C (alphabeta) C (alpha)} and (5,3)D {C (alphabeta) C (alpha)}{CON}HN, was explored to break the very high chemical shift degeneracy typically encountered for membrane proteins. It is shown that the 4D and 5D spectral information obtained rapidly from GFT and G(2)FT NMR experiments enables one to efficiently obtain (nearly) complete resonance assignments of membrane proteins.

  2. Alteration of phospholipids in the blood of patients with Duchenne muscular dystrophy (DMD): in vitro, high resolution31P NMR-based study.

    Science.gov (United States)

    Srivastava, Niraj Kumar; Mukherjee, Somnath; Sinha, Neeraj

    2016-12-01

    In vitro, high-resolution 31 P NMR (Nuclear Magnetic Resonance) spectroscopy-based analysis of phospholipids in serum is well recognized in leukemia, lymphoma, non-hematological cancers and renal cell carcinoma. In context of these studies, phospholipids were analyzed in blood of thirty-two (n = 32) patients with Duchenne muscular dystrophy (DMD) (Age, Mean ± SD; 8.0 ± 1.6 years) and sixteen (n = 16) healthy subjects (Age, Mean ± SD; 8.6 ± 2.3 years). Quantity of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and lyso-phosphatidylcholine (Lys-PC) was significantly higher (p DMD patients as compared to healthy subjects. There were no significant differences (p > 0.05) observed for the quantity of phospholipids in blood of gene deletion positive cases of DMD as compared to negative gene deletion cases of DMD. Quantity of phospholipids in negative gene deletion cases of DMD patients as well as DMD cases with positive gene deletion was significantly higher (p DMD from the healthy subjects on the basis of the quantity of phospholipids in blood. These observations may be useful in future for the development of new diagnostic method of DMD.

  3. Metabolic Effects of a 24-Week Energy-Restricted Intervention Combined with Low or High Dairy Intake in Overweight Women: An NMR-Based Metabolomics Investigation

    Directory of Open Access Journals (Sweden)

    Hong Zheng

    2016-02-01

    Full Text Available We investigated the effect of a 24-week energy-restricted intervention with low or high dairy intake (LD or HD on the metabolic profiles of urine, blood and feces in overweight/obese women by NMR spectroscopy combined with ANOVA-simultaneous component analysis (ASCA. A significant effect of dairy intake was found on the urine metabolome. HD intake increased urinary citrate, creatinine and urea excretion, and decreased urinary excretion of trimethylamine-N-oxide (TMAO and hippurate relative to the LD intake, suggesting that HD intake was associated with alterations in protein catabolism, energy metabolism and gut microbial activity. In addition, a significant time effect on the blood metabolome was attributed to a decrease in blood lipid and lipoprotein levels due to the energy restriction. For the fecal metabolome, a trend for a diet effect was found and a series of metabolites, such as acetate, butyrate, propionate, malonate, cholesterol and glycerol tended to be affected. Overall, even though these effects were not accompanied by a higher weight loss, the present metabolomics data reveal that a high dairy intake is associated with endogenous metabolic effects and effects on gut microbial activity that potentially impact body weight regulation and health. Moreover, ASCA has a great potential for exploring the effect of intervention factors and identifying altered metabolites in a multi-factorial metabolomic study.

  4. Study of acute biochemical effects of thallium toxicity in mouse urine by NMR spectroscopy.

    Science.gov (United States)

    Tyagi, Ritu; Rana, Poonam; Khan, Ahmad Raza; Bhatnagar, Deepak; Devi, M Memita; Chaturvedi, Shubhra; Tripathi, Rajendra P; Khushu, Subash

    2011-10-01

    Thallium (Tl) is a toxic heavy metal and its exposure to the human body causes physiological and biochemical changes due to its interference with potassium-dependent biological reactions. A high-resolution (1)H NMR spectroscopy based metabonomic approach has been applied for investigating acute biochemical effects caused by thallium sulfate (Tl(2)SO(4)). Male strain A mice were divided in three groups and received three doses of Tl(2)SO(4) (5, 10 and 20 mg kg(-1) b.w., i.p.). Urine samples collected at 3, 24, 72 and 96 h post-dose time points were analyzed by (1)H NMR spectroscopy. NMR spectral data were processed and analyzed using principal components analysis to represent biochemical variations induced by Tl(2)SO(4). Results showed Tl-exposed mice urine to have distinct metabonomic phenotypes and revealed dose- and time-dependent clustering of treated groups. The metabolic signature of urine analysis from Tl(2)SO(4)-treated animals exhibited an increase in the levels of creatinine, taurine, hippurate and β-hydroxybutyrate along with a decrease in energy metabolites trimethylamine and choline. These findings revealed Tl-induced disturbed gut flora, membrane metabolite, energy and protein metabolism, representing physiological dysfunction of vital organs. The present study indicates the great potential of NMR-based metabonomics in mapping metabolic response for toxicology, which could ultimately lead to identification of potential markers for Tl toxicity. Copyright © 2011 John Wiley & Sons, Ltd.

  5. Phytochemical diversity of cranberry (Vaccinium macrocarpon Aiton) cultivars by anthocyanin determination and metabolomic profiling with chemometric analysis.

    Science.gov (United States)

    Brown, Paula N; Murch, Susan J; Shipley, Paul

    2012-01-11

    Originally native to the eastern United States, American cranberry ( Vaccinium macrocarpon Aiton, family Ericaceae) cultivation of native and hybrid varieties has spread across North America. Herein is reported the phytochemical diversity of five cranberry cultivars (Stevens, Ben Lear, Bergman, Pilgrim, and GH1) collected in the Greater Vancouver Regional District, by anthocyanin content and UPLC-TOF-MS metabolomic profiling. The anthocyanin content for biological replicates (n = 5) was determined as 7.98 ± 5.83, Ben Lear; 7.02 ± 1.75, Bergman; 6.05 ± 2.51, GH1; 3.28 ± 1.88, Pilgrim; and 2.81 ± 0.81, Stevens. Using subtractive metabonomic algorithms 6481 compounds were found conserved across all varietals, with 136 (Ben Lear), 84 (Bergman), 91 (GH1), 128 (Pilgrim), and 165 (Stevens) unique compounds observed. Principal component analysis (PCA) did not differentiate varieties, whereas partial least-squares discriminate analysis (PLS-DA) exhibited clustering patterns. Univariate statistical approaches were applied to the data set, establishing significance of values and assessing quality of the models. Metabolomic profiling with chemometric analysis proved to be useful for characterizing metabonomic changes across cranberry varieties.

  6. Metabolomics study on the toxicity of Annona squamosa by ultraperformance liquid-chromatography high-definition mass spectrometry coupled with pattern recognition approach and metabolic pathways analysis.

    Science.gov (United States)

    Miao, Yun-Jie; Shi, Ye-Ye; Li, Fu-Qiang; Shan, Chen-Xiao; Chen, Yong; Chen, Jian-Wei; Li, Xiang

    2016-05-26

    Annona squamosa Linn (Annonaceae) is a commonly used and effective traditional Chinese medicine (TCM) especially in the South China. The seeds of Annona squamosa Linn (SAS) have been used as a folk remedy to treat "malignant sores" (cancer) in South of China, but they also have high toxicity on human body. To discover the potential biomarkers in the mice caused by SAS. We made metabonomics studies on the toxicity of SAS by ultraperformance liquid-chromatography high-definition mass spectrometry coupled with pattern recognition approach and metabolic pathways analysis. The significant difference in metabolic profiles and changes of metabolite biomarkers between the Control group and SAS group were well observed. 11 positive ions and 9 negative ions (P<0.05) were indicated based on UFLC-QTOF-HDMS. The metabolic pathways of SAS group are discussed according to the identified endogenous metabolites, and eight metabolic pathways are identified using Kyoto Encyclopedia of Genes and Genomes (KEGG). The present study demonstrates that metabonomics analysis could greatly facilitate and provide useful information for the further comprehensive understanding of the pharmacological activity and potential toxicity of SAS in the progress of them being designed to a new anti-tumor medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Metabonomic investigation of human Schistosoma mansoni infection

    DEFF Research Database (Denmark)

    Balog, Crina I.A.; Meissner, Axel; Göraler, Sibel

    2011-01-01

    involving a well-characterized cohort of 447 individuals from a rural area in Uganda near Lake Victoria with a high prevalence of Schistosoma mansoni, a species predominantly occurring in Africa including Madagascar and parts of South America. Cohort samples were collected from individuals at five time...

  8. GFT projection NMR based resonance assignment of membrane proteins: application to subunit c of E. coli F{sub 1}F{sub 0} ATP synthase in LPPG micelles

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Qi [State University of New York at Buffalo, Department of Chemistry (United States); Atreya, Hanudatta S. [NMR Research Centre, Indian Institute of Science (India); Kamen, Douglas E.; Girvin, Mark E. [Albert Einstein College of Medicine, Biochemistry Department (United States); Szyperski, Thomas [State University of New York at Buffalo, Department of Chemistry (United States)], E-mail: szypersk@chem.buffalo.edu

    2008-03-15

    G-matrix FT projection NMR spectroscopy was employed for resonance assignment of the 79-residue subunit c of the Escherichia coli F{sub 1}F{sub 0} ATP synthase embedded in micelles formed by lyso palmitoyl phosphatidyl glycerol (LPPG). Five GFT NMR experiments, that is, (3,2)D HNNCO, L-(4,3)D HNNC{sup {alpha}}{sup {beta}}C{sup {alpha}}, L-(4,3)D HNN(CO)C{sup {alpha}}{sup {beta}}C{sup {alpha}}, (4,2)D HACA(CO)NHN and (4,3)D HCCH, were acquired along with simultaneous 3D {sup 15}N, {sup 13}C{sup aliphatic}, {sup 13}C{sup aromatic}-resolved [{sup 1}H,{sup 1}H]-NOESY with a total measurement time of {approx}43 h. Data analysis resulted in sequence specific assignments for all routinely measured backbone and {sup 13}C{sup {beta}} shifts, and for 97% of the side chain shifts. Moreover, the use of two G{sup 2}FT NMR experiments, that is, (5,3)D HN{l_brace}N,CO{r_brace}{l_brace}C{sup {alpha}}{sup {beta}}C{sup {alpha}}{r_brace} and (5,3)D {l_brace}C{sup {alpha}}{sup {beta}}C{sup {alpha}}{r_brace}{l_brace}CON{r_brace}HN, was explored to break the very high chemical shift degeneracy typically encountered for membrane proteins. It is shown that the 4D and 5D spectral information obtained rapidly from GFT and G{sup 2}FT NMR experiments enables one to efficiently obtain (nearly) complete resonance assignments of membrane proteins.

  9. Fluorine NMR-based screening on cell membrane extracts.

    Science.gov (United States)

    Veronesi, Marina; Romeo, Elisa; Lambruschini, Chiara; Piomelli, Daniele; Bandiera, Tiziano; Scarpelli, Rita; Garau, Gianpiero; Dalvit, Claudio

    2014-02-01

    The possibility of measuring the action of inhibitors of specific enzymatic reactions in intact cells, cell lysates or membrane preparations represents a major advance in the lead discovery process. Despite the relevance of assaying in physiological conditions, only a small number of biophysical techniques, often requiring complex set-up, are applicable to these sample types. Here, we demonstrate the first application of n-fluorine atoms for biochemical screening (n-FABS), a homogeneous and versatile assay based on (19) F NMR spectroscopy, to the detection of high- and low-affinity inhibitors of a membrane enzyme in cell extracts and determination of their IC50 values. Our approach can allow the discovery of novel binding fragments against targets known to be difficult to purify or where membrane-association is required for activity. These results pave the way for future applications of the methodology to these relevant and complex biological systems. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Extraction of alkaloids for NMR-based profiling

    DEFF Research Database (Denmark)

    Yilmaz, Ali; Nyberg, Nils; Jaroszewski, Jerzy W.

    2012-01-01

    A museum collection of Cinchona cortex samples (n = 117), from the period 1850–1950, were extracted with a mixture of chloroform-d1, methanol-d4, water-d2, and perchloric acid in the ratios 5:5:1:1. The extracts were directly analyzed using 1H NMR spectroscopy (600 MHz) and the spectra evaluated ...

  11. Probing beer aging chemistry by nuclear magnetic resonance and multivariate analysis

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, J.A. [CICECO-Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Barros, A.S. [QOPNA-Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal); Carvalho, B.; Brandao, T. [UNICER, Bebidas de Portugal, Leca do Balio, 4466-955, S. Mamede de Infesta (Portugal); Gil, Ana M., E-mail: agil@ua.pt [CICECO-Department of Chemistry, University of Aveiro, Campus de Santiago, 3810-193 Aveiro (Portugal)

    2011-09-30

    Graphical abstract: The use of nuclear magnetic resonance (NMR) metabonomics for monitoring the chemical changes occurring in beer exposed to forced aging (at 45 deg. C for up to 18 days) is described. Both principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to the NMR spectra of beer recorded as a function of aging and an aging trend was observed. Inspection of PLS-DA loadings and peak integration revealed the importance of well known markers (e.g. 5-HMF) as well as of other compounds: amino acids, higher alcohols, organic acids, dextrins and some still unassigned spin systems. 2D correlation analysis enabled relevant compound variations to be confirmed and inter-compound correlations to be assessed, thus offering improved insight into the chemical aspects of beer aging. Highlights: {center_dot} Use of NMR metabonomics for monitoring the chemical changes occurring in beer exposed to forced aging. {center_dot} Compositional variations evaluated by principal component analysis and partial least squares-discriminant analysis. {center_dot} Results reveal importance of known markers and other compounds: amino and organic acids, higher alcohols, dextrins. {center_dot} 2D correlation analysis reveals inter-compound relationships, offering insight into beer aging chemistry. - Abstract: This paper describes the use of nuclear magnetic resonance (NMR) spectroscopy, in tandem with multivariate analysis (MVA), for monitoring the chemical changes occurring in a lager beer exposed to forced aging (at 45 deg. C for up to 18 days). To evaluate the resulting compositional variations, both principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to the NMR spectra of beer recorded as a function of aging and a clear aging trend was observed. Inspection of PLS-DA loadings and peak integration enabled the changing compounds to be identified, revealing the importance of well known

  12. Probing beer aging chemistry by nuclear magnetic resonance and multivariate analysis

    International Nuclear Information System (INIS)

    Rodrigues, J.A.; Barros, A.S.; Carvalho, B.; Brandao, T.; Gil, Ana M.

    2011-01-01

    Graphical abstract: The use of nuclear magnetic resonance (NMR) metabonomics for monitoring the chemical changes occurring in beer exposed to forced aging (at 45 deg. C for up to 18 days) is described. Both principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to the NMR spectra of beer recorded as a function of aging and an aging trend was observed. Inspection of PLS-DA loadings and peak integration revealed the importance of well known markers (e.g. 5-HMF) as well as of other compounds: amino acids, higher alcohols, organic acids, dextrins and some still unassigned spin systems. 2D correlation analysis enabled relevant compound variations to be confirmed and inter-compound correlations to be assessed, thus offering improved insight into the chemical aspects of beer aging. Highlights: · Use of NMR metabonomics for monitoring the chemical changes occurring in beer exposed to forced aging. · Compositional variations evaluated by principal component analysis and partial least squares-discriminant analysis. · Results reveal importance of known markers and other compounds: amino and organic acids, higher alcohols, dextrins. · 2D correlation analysis reveals inter-compound relationships, offering insight into beer aging chemistry. - Abstract: This paper describes the use of nuclear magnetic resonance (NMR) spectroscopy, in tandem with multivariate analysis (MVA), for monitoring the chemical changes occurring in a lager beer exposed to forced aging (at 45 deg. C for up to 18 days). To evaluate the resulting compositional variations, both principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were applied to the NMR spectra of beer recorded as a function of aging and a clear aging trend was observed. Inspection of PLS-DA loadings and peak integration enabled the changing compounds to be identified, revealing the importance of well known markers such as 5-hydroxymethylfurfural (5

  13. Metabolic profiling studies on the toxicological effects of realgar in rats by 1H NMR spectroscopy

    International Nuclear Information System (INIS)

    Wei Lai; Liao Peiqiu; Wu Huifeng; Li Xiaojing; Pei Fengkui; Li Weisheng; Wu Yijie

    2009-01-01

    The toxicological effects of realgar after intragastrical administration (1 g/kg body weight) were investigated over a 21 day period in male Wistar rats using metabonomic analysis of 1 H NMR spectra of urine, serum and liver tissue aqueous extracts. Liver and kidney histopathology examination and serum clinical chemistry analyses were also performed. 1 H NMR spectra and pattern recognition analyses from realgar treated animals showed increased excretion of urinary Kreb's cycle intermediates, increased levels of ketone bodies in urine and serum, and decreased levels of hepatic glucose and glycogen, as well as hypoglycemia and hyperlipoidemia, suggesting the perturbation of energy metabolism. Elevated levels of choline containing metabolites and betaine in serum and liver tissue aqueous extracts and increased serum creatine indicated altered transmethylation. Decreased urinary levels of trimethylamine-N-oxide, phenylacetylglycine and hippurate suggested the effects on the gut microflora environment by realgar. Signs of impairment of amino acid metabolism were supported by increased hepatic glutamate levels, increased methionine and decreased alanine levels in serum, and hypertaurinuria. The observed increase in glutathione in liver tissue aqueous extracts could be a biomarker of realgar induced oxidative injury. Serum clinical chemistry analyses showed increased levels of lactate dehydrogenase, aspartate aminotransferase, and alkaline phosphatase as well as increased levels of blood urea nitrogen and creatinine, indicating slight liver and kidney injury. The time-dependent biochemical variations induced by realgar were achieved using pattern recognition methods. This work illustrated the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by traditional Chinese medicine

  14. Metabolic profiling detects early effects of environmental and lifestyle exposure to cadmium in a human population

    Directory of Open Access Journals (Sweden)

    Ellis James K

    2012-06-01

    Full Text Available Abstract Background The 'exposome' represents the accumulation of all environmental exposures across a lifetime. Top-down strategies are required to assess something this comprehensive, and could transform our understanding of how environmental factors affect human health. Metabolic profiling (metabonomics/metabolomics defines an individual's metabolic phenotype, which is influenced by genotype, diet, lifestyle, health and xenobiotic exposure, and could also reveal intermediate biomarkers for disease risk that reflect adaptive response to exposure. We investigated changes in metabolism in volunteers living near a point source of environmental pollution: a closed zinc smelter with associated elevated levels of environmental cadmium. Methods High-resolution 1H NMR spectroscopy (metabonomics was used to acquire urinary metabolic profiles from 178 human volunteers. The spectral data were subjected to multivariate and univariate analysis to identify metabolites that were correlated with lifestyle or biological factors. Urinary levels of 8-oxo-deoxyguanosine were also measured, using mass spectrometry, as a marker of systemic oxidative stress. Results Six urinary metabolites, either associated with mitochondrial metabolism (citrate, 3-hydroxyisovalerate, 4-deoxy-erythronic acid or one-carbon metabolism (dimethylglycine, creatinine, creatine, were associated with cadmium exposure. In particular, citrate levels retained a significant correlation to urinary cadmium and smoking status after controlling for age and sex. Oxidative stress (as determined by urinary 8-oxo-deoxyguanosine levels was elevated in individuals with high cadmium exposure, supporting the hypothesis that heavy metal accumulation was causing mitochondrial dysfunction. Conclusions This study shows evidence that an NMR-based metabolic profiling study in an uncontrolled human population is capable of identifying intermediate biomarkers of response to toxicants at true environmental

  15. Characterisation of human embryonic stem cells conditioning media by 1H-nuclear magnetic resonance spectroscopy.

    Directory of Open Access Journals (Sweden)

    David A MacIntyre

    Full Text Available BACKGROUND: Cell culture media conditioned by human foreskin fibroblasts (HFFs provide a complex supplement of protein and metabolic factors that support in vitro proliferation of human embryonic stem cells (hESCs. However, the conditioning process is variable with different media batches often exhibiting differing capacities to maintain hESCs in culture. While recent studies have examined the protein complement of conditioned culture media, detailed information regarding the metabolic component of this media is lacking. METHODOLOGY/PRINCIPAL FINDINGS: Using a (1H-Nuclear Magnetic Resonance ((1H-NMR metabonomics approach, 32 metabolites and small compounds were identified and quantified in media conditioned by passage 11 HFFs (CMp11. A number of metabolites were secreted by HFFs with significantly higher concentration of lactate, alanine, and formate detected in CMp11 compared to non-conditioned media. In contrast, levels of tryptophan, folate and niacinamide were depleted in CMp11 indicating the utilisation of these metabolites by HFFs. Multivariate statistical analysis of the (1H-NMR data revealed marked age-related differences in the metabolic profile of CMp11 collected from HFFs every 24 h over 72 h. Additionally, the metabolic profile of CMp11 was altered following freezing at -20°C for 2 weeks. CM derived from passage 18 HFFs (CMp18 was found to be ineffective at supporting hESCs in an undifferentiated state beyond 5 days culture. Multivariate statistical comparison of CMp11 and CMp18 metabolic profiles enabled rapid and clear discrimination between the two media with CMp18 containing lower concentrations of lactate and alanine as well as higher concentrations of glucose and glutamine. CONCLUSIONS/SIGNIFICANCE: (1H-NMR-based metabonomics offers a rapid and accurate method of characterising hESC conditioning media and is a valuable tool for monitoring, controlling and optimising hESC culture media preparation.

  16. Trace analysis in complex mixtures using a high-component filtering strategy with liquid chromatography-mass spectrometry.

    Science.gov (United States)

    Zhang, Hui; Wang, Shao-Qing; Liu, Ying; Luo, Li-Ping; Liu, Peng; Qi, Lian-Wen; Li, Ping

    2012-11-01

    Trace constituents are widely present in complex mixtures, and trace analysis is challenging because of the unpredictable matrix. In this work, a high-component filtering strategy was developed for improved analysis of trace constituents in complex sample by liquid chromatography-mass spectrometry (LC-MS). Using a specifically designed chromatographic apparatus, the high-abundant fractions were filtered prior to LC-MS analysis. The samples complexity was reduced and the sample-loading amount for the rest low-level fractions can be considerably increased. The application of this approach was illustrated with an analytically challenging sample, a traditional Chinese herbal medicine named Compound Danshen Sample. We observed that the loss rate for 12 analytes during the filtering procedure ranged from 6.54 to 26.11%, but showed a stable repeatability with RSDanalysis, allowing six low compounds that cannot be quantified by the traditional methods to be tested by the filtering method. It can be predicted that the qualitative and quantitative trace analysis will be greatly improved when the loading samples is increased resulting from the filtration of high-level targets. The proposed strategy is promising to monitor trace constituents in diverse complex mixtures in the analytical field of pharmaceutics, metabonomics and environments. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Analysis of urinary metabolomic profiling for unstable angina pectoris disease based on nuclear magnetic resonance spectroscopy.

    Science.gov (United States)

    Li, Zhongfeng; Liu, Xinfeng; Wang, Juan; Gao, Jian; Guo, Shuzhen; Gao, Kuo; Man, Hongxue; Wang, Yingfeng; Chen, Jianxin; Wang, Wei

    2015-12-01

    (1)H NMR-based urinary metabolic profiling is used for investigating the unstable angina pectoris (UAP) metabolic signatures, in order to find out candidate biomarkers to facilitate medical diagnosis. In this work, 27 urine samples from UAP patients and 20 healthy controls were used. The metabolic profiles of the samples were analyzed by multivariate statistics analysis, including PCA, PLS-DA and OPLS-DA. The PCA analysis exhibited slight separation with R(2)X of 0.681 and Q2 of 0.251, while the PLS-DA (R(2)X = 0.121, R(2)Y = 0.931, and Q(2) = 0.661) and the OPLS-DA (R(2)X = 0.121, R(2)Y = 0.931, Q(2) = 0.653) demonstrated that the model showed good performance. By OPLS-DA, 20 metabolites were identified. A diagnostic model was further constructed using the receiver-operator characteristic (ROC) curves (AUC = 0.953), which exhibited a satisfying sensitivity of 92.6%, specificity of 90% and accuracy of 89.1%. The results demonstrated that the NMR-based metabolomics approach showed good performance in identifying diagnostic urinary biomarkers, providing new insights into the metabolic process related to UAP.

  18. Analysis of 2-(2-Phenylethyl)chromones by UPLC-ESI-QTOF-MS and Multivariate Statistical Methods in Wild and Cultivated Agarwood

    Science.gov (United States)

    Li, Yuanbin; Sheng, Nan; Wang, Lingli; Li, Shijie; Chen, Jiannan; Lai, Xiaoping

    2016-01-01

    Agarwood is the fragrant resinous material mainly formed from species of Aquilaria. 2-(2-phenylethyl)chromones, especially the highly oxidized 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, are the main representative compounds from agarwood. It is important to determine whether agarwood in trade is from cultivated trees or natural trees in the Convention on the International Trade in Endangered Species (CITES). We characterized the 2-(2-phenylethyl)chromones in agarwood by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC–ESI-QTOF-MS) and differentiated wild from cultivated agarwood by metabolomic analysis. A total of 141 chromones including 50 potentially new compounds were evaluated as belonging to four structural classes (unoxidized 2-(2-phenylethyl)chromones, 5,6,7,8-tetrahydro-2-(2-phenylethyl)-chromones, bi-2-(2-phenylethyl)chromones, and tri-2-(2-phenylethyl)chromones). The metabolic difference between wild and cultivated agarwood was analyzed by component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Fourteen markers of metabolisms in wild and cultivated agarwood were constructed (e.g., 6,7-dimethoxy-2-(2-phenylethyl)chromone, 6,8-dihydroxy-2-(2-phenylethyl)chromone, 6-methoxy-2-(2-phenylethyl)chromone, etc.). These results indicated that UPLC–ESI-QTOF-MS-based metabonomics analysis in agarwood may be useful for distinguishing wild agarwood from cultivated agarwood. PMID:27223280

  19. Analysis of 2-(2-Phenylethylchromones by UPLC-ESI-QTOF-MS and Multivariate Statistical Methods in Wild and Cultivated Agarwood

    Directory of Open Access Journals (Sweden)

    Yuanbin Li

    2016-05-01

    Full Text Available Agarwood is the fragrant resinous material mainly formed from species of Aquilaria. 2-(2-phenylethylchromones, especially the highly oxidized 5,6,7,8-tetrahydro-2-(2-phenylethylchromones, are the main representative compounds from agarwood. It is important to determine whether agarwood in trade is from cultivated trees or natural trees in the Convention on the International Trade in Endangered Species (CITES. We characterized the 2-(2-phenylethylchromones in agarwood by ultra-performance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC–ESI-QTOF-MS and differentiated wild from cultivated agarwood by metabolomic analysis. A total of 141 chromones including 50 potentially new compounds were evaluated as belonging to four structural classes (unoxidized 2-(2-phenylethylchromones, 5,6,7,8-tetrahydro-2-(2-phenylethyl-chromones, bi-2-(2-phenylethylchromones, and tri-2-(2-phenylethylchromones. The metabolic difference between wild and cultivated agarwood was analyzed by component analysis (PCA and orthogonal partial least squares discriminant analysis (OPLS-DA. Fourteen markers of metabolisms in wild and cultivated agarwood were constructed (e.g., 6,7-dimethoxy-2-(2-phenylethylchromone, 6,8-dihydroxy-2-(2-phenylethylchromone, 6-methoxy-2-(2-phenylethylchromone, etc.. These results indicated that UPLC–ESI-QTOF-MS-based metabonomics analysis in agarwood may be useful for distinguishing wild agarwood from cultivated agarwood.

  20. Metabolomic analysis of Echinacea spp. by 1H nuclear magnetic resonance spectrometry and multivariate data analysis technique.

    Science.gov (United States)

    Frédérich, Michel; Jansen, Céline; de Tullio, Pascal; Tits, Monique; Demoulin, Vincent; Angenot, Luc

    2010-01-01

    The genus Echinacea (Asteraceae) comprises about 10 species originally distributed in North America. Three species are very well known as they are used worldwide as medicinal plants: Echinacea purpurea, E. pallida, E. angustifolia. To discriminate between these three Echinacea species and E. simulata by (1)H NMR-based metabolomics. (1)H NMR and multivariate analysis techniques were applied to diverse Echinacea plants including roots and aerial parts, authentic plants, commercial plants and commercial dry extracts. Using the (1)H NMR metabolomics, it was possible, without previous evaporation or separation steps, to obtain a metabolic fingerprint to distinguish between species. A clear distinction between the three pharmaceutical species was possible and some useful metabolites were identified. (c) 2009 John Wiley & Sons, Ltd.

  1. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis.

    Science.gov (United States)

    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-ming; Chen, Nan; Zhang, Nai-xia

    2014-05-01

    To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to (1)H-NMR-based metabolomic analysis. Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The (1)H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines.

  2. Analysis

    DEFF Research Database (Denmark)

    Mathiesen, Brian Vad; Liu, Wen; Zhang, Xiliang

    2014-01-01

    three major technological changes: energy savings on the demand side, efficiency improvements in energy production, and the replacement of fossil fuels by various sources of renewable energy. Consequently, the analysis of these systems must include strategies for integrating renewable sources...

  3. Comprehensive NMR analysis of compositional changes of black garlic during thermal processing.

    Science.gov (United States)

    Liang, Tingfu; Wei, Feifei; Lu, Yi; Kodani, Yoshinori; Nakada, Mitsuhiko; Miyakawa, Takuya; Tanokura, Masaru

    2015-01-21

    Black garlic is a processed food product obtained by subjecting whole raw garlic to thermal processing that causes chemical reactions, such as the Maillard reaction, which change the composition of the garlic. In this paper, we report a nuclear magnetic resonance (NMR)-based comprehensive analysis of raw garlic and black garlic extracts to determine the compositional changes resulting from thermal processing. (1)H NMR spectra with a detailed signal assignment showed that 38 components were altered by thermal processing of raw garlic. For example, the contents of 11 l-amino acids increased during the first step of thermal processing over 5 days and then decreased. Multivariate data analysis revealed changes in the contents of fructose, glucose, acetic acid, formic acid, pyroglutamic acid, cycloalliin, and 5-(hydroxymethyl)furfural (5-HMF). Our results provide comprehensive information on changes in NMR-detectable components during thermal processing of whole garlic.

  4. Analysis

    CERN Document Server

    Maurin, Krzysztof

    1980-01-01

    The extraordinarily rapid advances made in mathematics since World War II have resulted in analysis becoming an enormous organism spread­ ing in all directions. Gone for good surely are the days of the great French "courses of analysis" which embodied the whole of the "ana­ lytical" knowledge of the times in three volumes-as the classical work of Camille Jordan. Perhaps that is why present-day textbooks of anal­ ysis are disproportionately modest relative to the present state of the art. More: they have "retreated" to the state before Jordan and Goursat. In recent years the scene has been changing rapidly: Jean Dieudon­ ne is offering us his monumentel Elements d'Analyse (10 volumes) written in the spirit of the great French Course d'Analyse. To the best of my knowledge, the present book is the only one of its size: starting from scratch-from rational numbers, to be precise-it goes on to the theory of distributions, direct integrals, analysis on com­ plex manifolds, Kahler manifolds, the theory of sheave...

  5. ¹H NMR and Multivariate Analysis for Geographic Characterization of Commercial Extra Virgin Olive Oil: A Possible Correlation with Climate Data.

    Science.gov (United States)

    Rongai, Domenico; Sabatini, Nadia; Del Coco, Laura; Perri, Enzo; Del Re, Paolo; Simone, Nicola; Marchegiani, Donato; Fanizzi, Francesco Paolo

    2017-11-07

    ¹H Nuclear Magnetic Resonance (NMR) spectroscopy coupled with multivariate analysis has been applied in order to investigate metabolomic profiles of more than 200 extravirgin olive oils (EVOOs) collected in a period of over four years (2009-2012) from different geographic areas. In particular, commercially blended EVOO samples originating from different Italian regions (Tuscany, Sicily and Apulia), as well as European (Spain and Portugal) and non-European (Tunisia, Turkey, Chile and Australia) countries. Multivariate statistical analysis (Principal Component Analisys (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA)) applied on the NMR data revealed the existence of marked differences between Italian (in particular from Tuscany, Sicily and Apulia regions) and foreign (in particular Tunisian) EVOO samples. A possible correlation with available climate data has been also investigated. These results aim to develop a powerful NMR-based tool able to protect Italian olive oil productions.

  6. 1H NMR and Multivariate Analysis for Geographic Characterization of Commercial Extra Virgin Olive Oil: A Possible Correlation with Climate Data

    Directory of Open Access Journals (Sweden)

    Domenico Rongai

    2017-11-01

    Full Text Available 1H Nuclear Magnetic Resonance (NMR spectroscopy coupled with multivariate analysis has been applied in order to investigate metabolomic profiles of more than 200 extravirgin olive oils (EVOOs collected in a period of over four years (2009–2012 from different geographic areas. In particular, commercially blended EVOO samples originating from different Italian regions (Tuscany, Sicily and Apulia, as well as European (Spain and Portugal and non-European (Tunisia, Turkey, Chile and Australia countries. Multivariate statistical analysis (Principal Component Analisys (PCA and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA applied on the NMR data revealed the existence of marked differences between Italian (in particular from Tuscany, Sicily and Apulia regions and foreign (in particular Tunisian EVOO samples. A possible correlation with available climate data has been also investigated. These results aim to develop a powerful NMR-based tool able to protect Italian olive oil productions.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Ethnopharmacology is one of the world’s fastest-growing scientific disciplines encompassing a diverse range of subjects. It links natural sciences research on medicinal, aromatic and toxic plants with socio-cultural studies and has often been associated with the development of new drugs...

  8. NMR Based Sensors for In Situ Monitoring of Changes in Groundwater Chemistry

    Science.gov (United States)

    2017-04-21

    The scientific principle exploited by these sensors is the relaxation of the nuclear magnetic resonance signals from these sensor materials in response...the individual nuclear magnetic moments of a sensor material align and can be manipulated using radiofrequency radiation. Once excited, a nuclear... material being studied (e.g., binding of water to a polymer surface or rigidity of a polymer) and by the presence of magnetic materials , including

  9. 1 H NMR-Based Kinetic-Mechanistic Study of the Intramolecular ...

    African Journals Online (AJOL)

    South African Journal of Chemistry. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 66 (2013) >. Log in or Register to get access to full text downloads.

  10. 13C-NMR Based Evaluation of the Electronic and Steric Interactions in Aromatic Amines

    Directory of Open Access Journals (Sweden)

    Borys Ośmiałowski

    2005-01-01

    Full Text Available Abstract: Chemical shifts of the para carbon atoms, δ(13C-4, in a series of aromatic amines were used to calculate the σp, σR and σOR substituent constants for different amino groups. 1-Pyrrolidino, N,N-di-n-butylamino and N,N-diethylamino groups were found to be the most strong electron-donors. ortho-Substitution decreases the donor properties of the amino group. The amino groups in 2,6-di-i-propylaniline and N,N-2,6-tetramethylaniline have very weak electron-donor properties. The nitrogen atom in benzoquinuclidine and N,N-dimethyl-2,6-di-i-propylaniline have an electron-acceptor character. The calculated substituent constants of the amino groups studied are consistent with the spectral and reactivity data available in literature. Values of δ(15N cannot be used as a direct measure of electronic effects of the N atom in anilines.

  11. 13C-NMR-Based Metabolomic Profiling of Typical Asian Soy Sauces

    Directory of Open Access Journals (Sweden)

    Ghulam Mustafa Kamal

    2016-09-01

    Full Text Available It has been a strong consumer interest to choose high quality food products with clear information about their origin and composition. In the present study, a total of 22 Asian soy sauce samples have been analyzed in terms of 13C-NMR spectroscopy. Spectral data were analyzed by multivariate statistical methods in order to find out the important metabolites causing the discrimination among typical soy sauces from different Asian regions. It was found that significantly higher concentrations of glutamate in Chinese red cooking (CR soy sauce may be the result of the manual addition of monosodium glutamate (MSG in the final soy sauce product. Whereas lower concentrations of amino acids, like leucine, isoleucine and valine, observed in CR indicate the different fermentation period used in production of CR soy sauce, on the other hand, the concentration of some fermentation cycle metabolites, such as acetate and sucrose, can be divided into two groups. The concentrations of these fermentation cycle metabolites were lower in CR and Singapore Kikkoman (SK, whereas much higher in Japanese shoyu (JS and Taiwan (China light (TL, which depict the influence of climatic conditions. Therefore, the results of our study directly indicate the influences of traditional ways of fermentation, climatic conditions and the selection of raw materials and can be helpful for consumers to choose their desired soy sauce products, as well as for researchers in further authentication studies about soy sauce.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-08-15

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

  13. Specificity and sensitivity of NMR based urinary metabolic biomarker for radiation injury

    International Nuclear Information System (INIS)

    Tyagi, Ritu; Watve, Apurva; Khushu, Subash; Rana, Poonam

    2016-01-01

    Increasing burden of natural background radiation and terrestrial radionuclides is a big threat of radiation exposure to the population at large. It is necessary to develop biomarker of ionizing radiation exposure that can be used for mass screening in the event of a radiological mass casualty incident. Metabolomics has already been proven as an excellent developing prospect for capturing diseases specific metabolic signatures as possible biomarkers. The aim of the present study is to evaluate the sensitivity and specificity of the urinary metabolites after whole body radiation exposure which can further be used as early predictive marker. The PLS-DA based ROC curve depicted taurine as a biomarker of early radiation injury. This study along with other 'omics' technique will be useful to help design strategies for non-invasive radiation biodosimetry through metabolomics in human populations

  14. Polyfluorinated amino acids for sensitive 19F NMR-based screening and kinetic measurements.

    Science.gov (United States)

    Papeo, Gianluca; Giordano, Patrizia; Brasca, Maria Gabriella; Buzzo, Ferdinando; Caronni, Dannica; Ciprandi, Franco; Mongelli, Nicola; Veronesi, Marina; Vulpetti, Anna; Dalvit, Claudio

    2007-05-02

    Two novel series of polyfluorinated amino acids (PFAs) were designed and synthesized according to a very short and scalable synthetic sequence. The advantages and limitations of these moieties for screening purposes are presented and discussed. The potential applications of these PFAs were tested with their incorporation into small arginine-containing peptides that represent suitable substrates for the enzyme trypsin. The enzymatic reactions were monitored by 19F NMR spectroscopy, using the 3-FABS (three fluorine atoms for biochemical screening) technique. The high sensitivity achieved with these PFAs permits a reduction in substrate concentration required for 3-FABS. This is relevant in the utilization of 3-FABS in fragment-based screening for identification of small scaffolds that bind weakly to the receptor of interest. The large dispersion of 19F isotropic chemical shifts allows the simultaneous measurement of the efficiency of the different substrates, thus identifying the best substrate for screening purposes. Furthermore, the knowledge of KM and Kcat for the different substrates allows the identification of the structural motifs responsible for the binding affinity to the receptor and those affecting the chemical steps in enzymatic catalysis. This enables the construction of suitable pharmacophores that can be used for designing nonpeptidic inhibitors with high affinity for the enzyme or molecules that mimic the transition state. The novel PFAs can also find useful application in the FAXS (fluorine chemical shift anisotropy and exchange for screening) experiment, a 19F-based competition binding assay for the detection of molecules that inhibit the interaction between two proteins.

  15. Recent developments in solution nuclear magnetic resonance (NMR)-based molecular biology.

    Science.gov (United States)

    Ziarek, Joshua J; Baptista, Diego; Wagner, Gerhard

    2018-01-01

    Visualizing post-translational modifications, conformations, and interaction surfaces of protein structures at atomic resolution underpins the development of novel therapeutics to combat disease. As computational resources expand, in silico calculations coupled with experimentally derived structures and functional assays have led to an explosion in structure-based drug design (SBDD) with several compounds in clinical trials. It is increasingly clear that "hidden" transition-state structures along activation trajectories can be harnessed to develop novel classes of allosteric inhibitors. The goal of this mini-review is to empower the clinical researcher with a general knowledge of the strengths and weaknesses of nuclear magnetic resonance (NMR) spectroscopy in molecular medicine. Although NMR can determine protein structures at atomic resolution, its unrivaled strength lies in sensing subtle changes in a nuclei's chemical environment as a result of intrinsic conformational dynamics, solution conditions, and binding interactions. These can be recorded at atomic resolution, without explicit structure determination, and then incorporated with static structures or molecular dynamics simulations to produce a complete biological picture.

  16. 1H NMR- based metabolite profiling of tropane alkaloids in Duboisia spec.

    OpenAIRE

    Ullrich, Sophie Friederike; Rothauer, Andreas; Kayser, Oliver

    2016-01-01

    Duboisia R.Br. (Solanaceae) is the main source of the tropane alkaloid scopolamine, which is an important precursor of various active pharmaceutical ingredients due to its anticholinergic properties. As only little is known about the metabolite composition among the different species, NMRbased metabolic profiling was done in order to elucidate primary and secondary metabolism in Duboisia especially focusing on the tropane alkaloid pathway. For this purpose, plants of five different genotypes ...

  17. 1 H NMR-Based Kinetic-Mechanistic Study of the Intramolecular ...

    African Journals Online (AJOL)

    A 1H NMR study of the acid-catalyzed, intramolecular trans-esterification between isomeric 2-exo-3-exo-dihydroxybornane monoacrylate esters has afforded insights into the reaction mechanism and permitted the determination of kinetic and thermodynamic parameters for the pseudo-first-order processes. KEYWORDS ...

  18. NMR-based Enantiodifferentiation of Chiral trans-2-Phenylcyclopropane Derivatives Using a Chiral Lanthanide Shift Reagent

    International Nuclear Information System (INIS)

    Cho, Nam Sook; Kim, Hyun Sook; Song, Mi Sook

    2011-01-01

    In contrast with optical methods, there is no need to characterize the pure enantiomers. Instead, the NMR method makes use of chiral reagents that convert a mixture of enantiomers into a mixture of diastereomeric complexes. Integration of the resulting NMR spectra yields a direct measurement of enantiomeric purity as long as there is a sufficiently large difference between the chemical shifts of the two diastereoisomeric complexes to produce baseline-resolved peaks. Absolute enantiomeric configurations can also be determined using this method. Chiral lanthanide shift reagents have been used since the 1970s to form addition complexes with various compounds through interactions with electron donor sites. Lanthanide-induced, pseudo-contact shifts (LIS) are a function of the distance, r, between the nuclei under observation and the lanthanide center, and the angle, θ, between the line connecting the metal ion with the observed nucleus and the line representing the CLSR magnetic axis

  19. GC/TOFMS analysis of metabolites in serum and urine reveals metabolic perturbation of TCA cycle in db/db mice involved in diabetic nephropathy.

    Science.gov (United States)

    Li, Mengjie; Wang, Xufang; Aa, Jiye; Qin, Weisong; Zha, Weibin; Ge, Yongchun; Liu, Linsheng; Zheng, Tian; Cao, Bei; Shi, Jian; Zhao, Chunyan; Wang, Xinwen; Yu, Xiaoyi; Wang, Guangji; Liu, Zhihong

    2013-06-01

    Early diagnosis of diabetic nephropathy (DN) is difficult although it is of crucial importance to prevent its development. To probe potential markers and the underlying mechanism of DN, an animal model of DN, the db/db mice, was used and serum and urine metabolites were profiled using gas chromatography/time-of-flight mass spectrometry. Metabolic patterns were evaluated based on serum and urine data. Principal component analysis of the data revealed an obvious metabonomic difference between db/db mice and controls, and db/db mice showed distinctly different metabolic patterns during the progression from diabetes to early, medium, and later DN. The identified metabolites discriminating between db/db mice and controls suggested that db/db mice have perturbations in the tricarboxylic acid cycle (TCA, citrate, malate, succinate, and aconitate), lipid metabolism, glycolysis, and amino acid turnover. The db/db mice were characterized by acidic urine, high TCA intermediates in serum at week 6 and a sharp decline thereafter, and gradual elevation of free fatty acids in the serum. The sharp drop of serum TCA intermediates from week 6 to 8 indicated the downregulated glycolysis and insulin resistance. However, urinary TCA intermediates did not decrease in parallel with those in the serum from week 6 to 10, and an increased portion of TCA intermediates in the serum was excreted into the urine at 8, 10, and 12 wk than at 6 wk, indicating kidney dysfunction occurred. The relative abundances of TCA intermediates in urine relative to those in serum were suggested as an index of renal damage.

  20. Dietary exposure to a low dose of pesticides alone or as a mixture: the biological metabolic fingerprint and impact on hematopoiesis.

    Science.gov (United States)

    Demur, C; Métais, B; Canlet, C; Tremblay-Franco, M; Gautier, R; Blas-Y-Estrada, F; Sommer, C; Gamet-Payrastre, L

    2013-06-07

    Consumers are exposed to a mixture of pesticides through their food intake. These compounds are considered risk factors for human health, and the impact of dietary exposure to low doses of pesticide mixtures remains poorly understood. For this study we developed a mouse model to mimic consumer exposure in order to compare the effect of pesticides both alone or combined at doses corresponding to their Acceptable Daily Intake value. Female mice were exposed to pesticides throughout gestation and lactation. After weaning pups were fed the same pesticide-enriched diet their mothers had received for an additional 11 weeks. A metabonomic approach using (1)H NMR-based analysis of plasma showed that exposure to each pesticide produced a specific metabolic fingerprint in adult offspring. Discriminant metabolites between groups were glucose or lactate, choline, glycerophosphocholine and phosphocholine. Interestingly, metabolite differences were observed as early as weaned animals that had not yet been directly exposed themselves. Studies of the hematopoietic system revealed that dietary exposure to one particular pesticide, endosulfan, produced a significant decrease in red blood cell and hemoglobin levels, consistent with hemolytic anemia. Moreover, cell signaling profiles of bone marrow progenitors were also clearly affected. Expression of cell signaling proteins such as P35, CDC27, FAK, P38 MAP kinase, calcineurin and caspase as well as proteins involved in the stability or structure of the cytoskeleton (vinculin, MAP2) was changed upon dietary exposure to pesticides. Finally, we found that dietary exposure to a mixture of pesticides had effects that differed and were often lesser or equal to that of the most efficient pesticide (endosulfan), suggesting that the effect of pesticide mixtures cannot always be predicted from the combined effects of their constituent compounds. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Metabolic fingerprinting of Tussilago farfara L. using ¹H-NMR spectroscopy and multivariate data analysis.

    Science.gov (United States)

    Zhi, Hai-Juan; Qin, Xue-Mei; Sun, Hai-Feng; Zhang, Li-Zeng; Guo, Xiao-Qing; Li, Zhen-Yu

    2012-01-01

    The flower bud of Tussilago farfara L. is widely used for the treatment of coughs, bronchitis and asthmatic disorders in traditional Chinese medicine. In Europe, the plant has been used as herbal remedies for virtually the same applications, but the leaves are preferred over flowers. To systematically evaluate the chemical profiles of Tusssilago farfara leaves and flowers along with the identification of the polar and non-polar metabolites. Metabolic profiling carried out by means of ¹H-NMR spectroscopy and multivariate data analysis was applied to crude extracts from flowers and leaves. Metabolites were identified directly from the crude extracts through one-dimensional and two-dimensional NMR spectra. A broad range of metabolites were detected without any chromatographic separation. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) of ¹H-NMR data provided a clear separation between the samples. The corresponding loadings plot indicated that higher levels of phenylpropanoids, amino acids, organic acids and fatty acids, as well as lower levels of sugars, terpenoids and sterols were present in the leaves, as compared with flowers. For the flowers, more phenylpropanoids were present in fully open flowers, while more sugars and fatty acids were present in flower buds. NMR spectra (one- and two-dimensional) are useful for identifying metabolites, especially for the overlapped signals. The NMR-based metabolomics approach has great potential for chemical comparison study of the metabolome of herbal drugs. Copyright © 2012 John Wiley & Sons, Ltd.

  2. CRAFT (complete reduction to amplitude frequency table)--robust and time-efficient Bayesian approach for quantitative mixture analysis by NMR.

    Science.gov (United States)

    Krishnamurthy, Krish

    2013-12-01

    The intrinsic quantitative nature of NMR is increasingly exploited in areas ranging from complex mixture analysis (as in metabolomics and reaction monitoring) to quality assurance/control. Complex NMR spectra are more common than not, and therefore, extraction of quantitative information generally involves significant prior knowledge and/or operator interaction to characterize resonances of interest. Moreover, in most NMR-based metabolomic experiments, the signals from metabolites are normally present as a mixture of overlapping resonances, making quantification difficult. Time-domain Bayesian approaches have been reported to be better than conventional frequency-domain analysis at identifying subtle changes in signal amplitude. We discuss an approach that exploits Bayesian analysis to achieve a complete reduction to amplitude frequency table (CRAFT) in an automated and time-efficient fashion - thus converting the time-domain FID to a frequency-amplitude table. CRAFT uses a two-step approach to FID analysis. First, the FID is digitally filtered and downsampled to several sub FIDs, and secondly, these sub FIDs are then modeled as sums of decaying sinusoids using the Bayesian approach. CRAFT tables can be used for further data mining of quantitative information using fingerprint chemical shifts of compounds of interest and/or statistical analysis of modulation of chemical quantity in a biological study (metabolomics) or process study (reaction monitoring) or quality assurance/control. The basic principles behind this approach as well as results to evaluate the effectiveness of this approach in mixture analysis are presented. Copyright © 2013 John Wiley & Sons, Ltd.

  3. Enhanced NMR-based profiling of polyphenols in commercially available grape juices using solid-phase extraction

    NARCIS (Netherlands)

    Savage, A.K.; Duynhoven, van J.P.M.; Tucker, G.; Daykin, C.

    2011-01-01

    Grapes and related products, such as juices, and in particular, their polyphenols, have previously been associated with many health benefits, such as protection against cardiovascular disease. Within grapes, a large range of structurally diverse polyphenols can be present, and their characterisation

  4. Development of a Novel NMR-based Rheb GTPase Assay and Molecular Characterization of TSC2 GAP Activity

    Science.gov (United States)

    2010-05-01

    activation enthalpy by TSC2-GAP ( DDH ‡ = −46.3 kJ/mol) was largely offset by an unfavorable decrease in activation entropy (−TDDS‡ = 39.5 kJ/mol at 25°C...is less potent than Ras ( DDH ‡ = −16.9 kJ/mol for Rheb compared to DDH ‡ = −21.7 kJ/mol for Ras), resulting in a higher free energy of activation (99.9

  5. NMR-based metabolite profiling of human milk: A pilot study of methods for investigating compositional changes during lactation

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Junfang [Department of Chemistry, Umeå University (Sweden); Domellöf, Magnus [Department of Clinical Sciences, Pediatrics, Umeå University (Sweden); Zivkovic, Angela M. [Foods for Health Institute, University of California, Davis, CA (United States); Department of Nutrition, University of California, Davis, CA (United States); Larsson, Göran [Department of Medical Biochemistry and Biophysics, Unit of Research, Education and Development-Östersund, Umeå University (Sweden); Öhman, Anders, E-mail: anders.ohman01@umu.se [Department of Pharmacology and Clinical Neuroscience, Umeå University (Sweden); Nording, Malin L., E-mail: malin.nording@umu.se [Department of Chemistry, Umeå University (Sweden)

    2016-01-15

    Low-molecular-weight metabolites in human milk are gaining increasing interest in studies of infant nutrition. In the present study, the milk metabolome from a single mother was explored at different stages of lactation. Metabolites were extracted from sample aliquots using either methanol/water (MeOH/H{sub 2}O) extraction or ultrafiltration. Nuclear magnetic resonance (NMR) spectroscopy was used for metabolite identification and quantification, and multi- and univariate statistical data analyses were used to detect changes over time of lactation. Compared to MeOH/H{sub 2}O extraction, ultrafiltration more efficiently reduced the interference from lipid and protein resonances, thereby enabling the identification and quantification of 36 metabolites. The human milk metabolomes at the early (9–24 days after delivery) and late (31–87 days after delivery) stages of lactation were distinctly different according to multi- and univariate statistics. The late lactation stage was characterized by significantly elevated concentrations of lactose, choline, alanine, glutamate, and glutamine, as well as by reduced levels of citrate, phosphocholine, glycerophosphocholine, and N-acetylglucosamine. Our results indicate that there are significant compositional changes of the human milk metabolome also in different phases of the matured lactation stage. These findings complement temporal studies on the colostrum and transitional metabolome in providing a better understanding of the nutritional variations received by an infant. - Highlights: • 36 metabolites were simultaneously quantified in human milk by NMR. • Ultrafiltration more efficiently reduces interferences than MeOH/H{sub 2}O extraction. • Compositional changes of the human milk exist during the matured lactation stage.

  6. NMR-based metabolite profiling of human milk: A pilot study of methods for investigating compositional changes during lactation

    International Nuclear Information System (INIS)

    Wu, Junfang; Domellöf, Magnus; Zivkovic, Angela M.; Larsson, Göran; Öhman, Anders; Nording, Malin L.

    2016-01-01

    Low-molecular-weight metabolites in human milk are gaining increasing interest in studies of infant nutrition. In the present study, the milk metabolome from a single mother was explored at different stages of lactation. Metabolites were extracted from sample aliquots using either methanol/water (MeOH/H 2 O) extraction or ultrafiltration. Nuclear magnetic resonance (NMR) spectroscopy was used for metabolite identification and quantification, and multi- and univariate statistical data analyses were used to detect changes over time of lactation. Compared to MeOH/H 2 O extraction, ultrafiltration more efficiently reduced the interference from lipid and protein resonances, thereby enabling the identification and quantification of 36 metabolites. The human milk metabolomes at the early (9–24 days after delivery) and late (31–87 days after delivery) stages of lactation were distinctly different according to multi- and univariate statistics. The late lactation stage was characterized by significantly elevated concentrations of lactose, choline, alanine, glutamate, and glutamine, as well as by reduced levels of citrate, phosphocholine, glycerophosphocholine, and N-acetylglucosamine. Our results indicate that there are significant compositional changes of the human milk metabolome also in different phases of the matured lactation stage. These findings complement temporal studies on the colostrum and transitional metabolome in providing a better understanding of the nutritional variations received by an infant. - Highlights: • 36 metabolites were simultaneously quantified in human milk by NMR. • Ultrafiltration more efficiently reduces interferences than MeOH/H 2 O extraction. • Compositional changes of the human milk exist during the matured lactation stage.

  7. NMR-Based Amide Hydrogen-Deuterium Exchange Measurements for Complex Membrane Proteins: Development and Critical Evaluation

    Science.gov (United States)

    Czerski, Lech; Vinogradova, Olga; Sanders, Charles R.

    2000-01-01

    A method for measuring site-specific amide hydrogen-deuterium exchange rates for membrane proteins in bilayers is reported and evaluated. This method represents an adaptation and extension of the approach of Dempsey and co-workers (Biophys. J. 70, 1777-1788 (1996)) and is based on reconstituting 15N-labeled membrane proteins into phospholipid bilayers, followed by lyophilization and rehydration with D2O or H2O (control). Following incubation for a time t under hydrated conditions, samples are again lyophilized and then solubilized in an organic solvent system, where 1H-15N HSQC spectra are recorded. Comparison of spectra from D2O-exposed samples to spectra from control samples yields the extent of the H-D exchange which occurred in the bilayers during time t. Measurements are site specific if specific 15N labeling is used. The first part of this paper deals with the search for a suitable solvent system in which to solubilize complex membrane proteins in an amide "exchange-trapped" form for NMR quantitation of amide peak intensities. The second portion of the paper documents application of the overall procedure to measuring site-specific amide exchange rates in diacylglycerol kinase, a representative integral membrane protein. Both the potential usefulness and the significant limitations of the new method are documented.

  8. An NMR-based scoring function improves the accuracy of binding pose predictions by docking by two orders of magnitude

    Energy Technology Data Exchange (ETDEWEB)

    Orts, Julien [EMBL, Structure and Computational Biology Unit (Germany); Bartoschek, Stefan [Industriepark Hoechst, Sanofi-Aventis Deutschland GmbH, R and D LGCR/Parallel Synthesis and Natural Products (Germany); Griesinger, Christian [Max Planck Institute for Biophysical Chemistry (Germany); Monecke, Peter [Industriepark Hoechst, Sanofi-Aventis Deutschland GmbH, R and D LGCR/Structure, Design and Informatics (Germany); Carlomagno, Teresa, E-mail: teresa.carlomagno@embl.de [EMBL, Structure and Computational Biology Unit (Germany)

    2012-01-15

    Low-affinity ligands can be efficiently optimized into high-affinity drug leads by structure based drug design when atomic-resolution structural information on the protein/ligand complexes is available. In this work we show that the use of a few, easily obtainable, experimental restraints improves the accuracy of the docking experiments by two orders of magnitude. The experimental data are measured in nuclear magnetic resonance spectra and consist of protein-mediated NOEs between two competitively binding ligands. The methodology can be widely applied as the data are readily obtained for low-affinity ligands in the presence of non-labelled receptor at low concentration. The experimental inter-ligand NOEs are efficiently used to filter and rank complex model structures that have been pre-selected by docking protocols. This approach dramatically reduces the degeneracy and inaccuracy of the chosen model in docking experiments, is robust with respect to inaccuracy of the structural model used to represent the free receptor and is suitable for high-throughput docking campaigns.

  9. Discovery of selective ligands for telomeric RNA G-quadruplexes (TERRA) through 19F-NMR based fragment screening.

    Science.gov (United States)

    Garavís, Miguel; López-Méndez, Blanca; Somoza, Alvaro; Oyarzabal, Julen; Dalvit, Claudio; Villasante, Alfredo; Campos-Olivas, Ramón; González, Carlos

    2014-07-18

    Telomeric repeat-containing RNA (TERRA) is a novel and very attractive antitumoral target. Here, we report the first successful application of (19)F-NMR fragment-based screening to identify chemically diverse compounds that bind to an RNA molecule such as TERRA. We have built a library of 355 fluorinated fragments, and checked their interaction with a long telomeric RNA as a target molecule. The screening resulted in the identification of 20 hits (hit rate of 5.6%). For a number of binders, their interaction with TERRA was confirmed by (19)F- and (1)H NMR as well as by CD melting experiments. We have also explored the selectivity of the ligands for RNA G-quadruplexes and found that some of the hits do not interact with other nucleic acids such as tRNA and duplex DNA and, most importantly, favor the propeller-like parallel conformation in telomeric DNA G-quadruplexes. This suggests a selective recognition of this particular quadruplex topology and that different ligands may recognize specific sites in propeller-like parallel G-quadruplexes. Such features make some of the resulting binders promising lead compounds for fragment based drug discovery.

  10. Metabonomics of Pig Blood Plasma Following Whole Body Exposure to Low Levels of Gb Vapor

    National Research Council Canada - National Science Library

    Bevilacqua, Vicky L; D'Onofrio, Terreiice G; Jakubowski, K. M; Hulet, Stanley W; Maguire, Kelly J; Edwards, Jennifer L; Laramee, James A; Brickhouse, Mark D

    2005-01-01

    ...), for which complex data must be analyzed. Therefore, we have begun an exploration of the use of chemometrics for the correlation of metabolic change with low-level CWA exposure in animal models...

  11. NMR analysis of male fathead minnow urinary metabolites: A potential approach for studying impacts of chemical exposures

    Energy Technology Data Exchange (ETDEWEB)

    Ekman, D.R. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States)], E-mail: ekman.drew@epa.gov; Teng, Q. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States); Jensen, K.M.; Martinovic, D.; Villeneuve, D.L.; Ankley, G.T. [Mid-Continent Ecology Division, U.S. EPA, 6201 Congdon Boulevard, Duluth, MN 55804 (United States); Collette, T.W. [Ecosystems Research Division, U.S. EPA, 960 College Station Road, Athens, GA 30605 (United States)

    2007-11-30

    The potential for profiling metabolites in urine from male fathead minnows (Pimephales promelas) to assess chemical exposures was explored using nuclear magnetic resonance (NMR) spectroscopy. Both one-dimensional (1D) and two-dimensional (2D) NMR spectroscopy was used for the assignment of metabolites in urine from unexposed fish. Because fathead minnow urine is dilute, we lyophilized these samples prior to analysis. Furthermore, 1D {sup 1}H NMR spectra of unlyophilized urine from unexposed male fathead minnow and Sprague-Dawley rat were acquired to qualitatively compare rat and fish metabolite profiles and to provide an estimate of the total urinary metabolite pool concentration difference. As a small proof-of-concept study, lyophilized urine samples from male fathead minnows exposed to three different concentrations of the antiandrogen vinclozolin were analyzed by 1D {sup 1}H NMR to assess exposure-induced changes. Through a combination of principal components analysis (PCA) and measurements of {sup 1}H NMR peak intensities, several metabolites were identified as changing with statistical significance in response to exposure. Among those changes occurring in response to exposure to the highest concentration (450 {mu}g/L) of vinclozolin were large increases in taurine, lactate, acetate, and formate. These increases coincided with a marked decrease in hippurate, a combination potentially indicative of hepatotoxicity. The results of these investigations clearly demonstrate the potential utility of an NMR-based approach for assessing chemical exposures in male fathead minnow, using urine collected from individual fish.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  14. Noninvasive analysis of metabolic changes following nutrient input into diverse fish species, as investigated by metabolic and microbial profiling approaches

    Directory of Open Access Journals (Sweden)

    Taiga Asakura

    2014-10-01

    Full Text Available An NMR-based metabolomic approach in aquatic ecosystems is valuable for studying the environmental effects of pharmaceuticals and other chemicals on fish. This technique has also contributed to new information in numerous research areas, such as basic physiology and development, disease, and water pollution. We evaluated the microbial diversity in various fish species collected from Japan’s coastal waters using next-generation sequencing, followed by evaluation of the effects of feed type on co-metabolic modulations in fish-microbial symbiotic ecosystems in laboratory-scale experiments. Intestinal bacteria of fish in their natural environment were characterized (using 16S rRNA genes for trophic level using pyrosequencing and noninvasive sampling procedures developed to study the metabolism of intestinal symbiotic ecosystems in fish reared in their environment. Metabolites in feces were compared, and intestinal contents and feed were annotated based on HSQC and TOCSY using SpinAssign and network analysis. Feces were characterized by species and varied greatly depending on the feeding types. In addition, feces samples demonstrated a response to changes in the time series of feeding. The potential of this approach as a non-invasive inspection technique in aquaculture is suggested.

  15. Metabolomics coupled with similarity analysis advances the elucidation of the cold/hot properties of traditional Chinese medicines.

    Science.gov (United States)

    Jia, Yan; Zhang, Zheng-Zheng; Wei, Yu-Hai; Xue-Mei, Qin; Li, Zhen-Yu

    2017-08-01

    It recently becomes an important and urgent mission for modern scientific research to identify and explain the theory of traditional Chinese medicine (TCM), which has been utilized in China for more than four millennia. Since few works have been contributed to understanding the TCM theory, the mechanism of actions of drugs with cold/hot properties remains unclear. In the present study, six kinds of typical herbs with cold or hot properties were orally administered into mice, and serum and liver samples were analyzed using an untargeted nuclear magnetic resonance (NMR) based metabolomics approach coupled with similarity analysis. This approach was performed to identify and quantify changes in metabolic pathways to elucidate drug actions on the treated mice. Our results showed that those drugs with same property exerted similar effects on the metabolic alterations in mouse serum and liver samples, while drugs with different property showed different effects. The effects of herbal medicines with cold/hot properties were exerted by regulating the pathways linked to glycometabolism, lipid metabolism, amino acids metabolism and other metabolic pathways. The results elucidated the differences and similarities of drugs with cold/hot properties, providing useful information on the explanation of medicinal properties of these TCMs. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  16. Quality assessment of Polygonum cuspidatum and Polygonum multiflorum by 1H NMR metabolite fingerprinting and profiling analysis.

    Science.gov (United States)

    Frédérich, Michel; Wauters, Jean-Noël; Tits, Monique; Jason, Charlotte; de Tullio, Pascal; Van der Heyden, Yvan; Fan, Guorong; Angenot, Luc

    2011-01-01

    The quality assessment and control of traditional Chinese medicines (TCM) nowadays receives a great deal of attention worldwide and particularly in Europe with its increasing local use. Polygonum cuspidatum Siebold & Zucc. and Polygonum multiflorum Thunb. are two members of the Polygonaceae family, which are widely used as Chinese medicinal plants. The aim of this study was to achieve an overview of the quality of P. cuspidatum and P. multiflorum samples available on the Chinese market and to identify important metabolites for their discrimination, using (1)H NMR-based metabolomics. (1)H NMR and multivariate analysis techniques were applied to almost 60 plant samples collected in different places in China. Using (1)H NMR metabolomics, it was possible, without previous evaporation or separation steps, to obtain metabolic fingerprints to distinguish between the species. The important metabolites for discrimination were stilbene derivatives. Finally, a clear distinction between the two species was possible and the discriminant metabolites were identified. © Georg Thieme Verlag KG Stuttgart · New York.

  17. A conformational NMR analysis of methymycin aglycones: complete and unambiguous assignments of stereochemically diverse glycosylated methymycin analogs by 1D and 2D NMR techniques and molecular modeling.

    Science.gov (United States)

    Akhmedov, Novruz G; Gannett, Peter M; Wu, Bulan; Cummings, Matthew M; Train, Brian C

    2013-03-01

    The (1)H and (13)C NMR spectra of 10-deoxymethynolide (1), 8.9-dihydro-10-deoxymethynolide (2) and its glycosylated derivatives (3-9) were analyzed using gradient-selected NMR techniques, including 1D TOCSY, gCOSY, 1D NOESY (DPFGSENOE), NOESY, gHMBC, gHSQC and gHSQC-TOCSY. The NMR spectral parameters (chemical shifts and coupling constants) of 1-9 were determined by iterative analysis. For the first time, complete and unambiguous assignment of the (1)H NMR spectrum of 10-deoxymethynolide (1) has been achieved in CDCl(3), CD(3)OD and C(6)D(6) solvents. The (1)H NMR spectrum of 8,9-dihydro-10-deoxymethynolide (2) was recorded in CDCl(3), (CD(3))(2)CO and CD(3)OD solutions to determine the conformation. NMR-based conformational analysis of 1 and 2 in conjugation with molecular modeling concluded that the 12-membered ring of the macrolactones may predominantly exist in a single stable conformation in all solvents examined. In all cases, a change in solvent caused only small changes in chemical shifts and coupling constants, suggesting that all glycosylated methymycin analogs exist with similar conformations of the aglycone ring in solution. Copyright © 2013 John Wiley & Sons, Ltd.

  18. Comparative analysis of the proximate and elemental composition of the blue crab Callinectes sapidus, the warty crab Eriphia verrucosa, and the edible crab Cancer pagurus

    Directory of Open Access Journals (Sweden)

    Maurizio Zotti

    2016-02-01

    Full Text Available The proximate composition and element contents of claw muscle tissue of Atlantic blue crabs (Callinectes sapidus were compared with the native warty crab (Eriphia verrucosa and the commercially edible crab (Cancer pagurus. The scope of the analysis was to profile the chemical characteristics and nutritive value of the three crab species. Elemental fingerprints showed significant inter-specific differences, whereas non-significant variations in the moisture and ash contents were observed. In the blue crab, protein content was significantly lower than in the other two species, while its carbon content resulted lower than that characterizing only the warty crab. Among micro-elements, Ba, Cr, Cu, Li, Mn, Ni, and Pb showed extremely low concentrations and negligible among-species differences. Significant inter-specific differences were observed for Na, Sr, V, Ba, Cd and Zn; in particular, cadmium and zinc were characterized in the blue crab by concentrations significantly lower than in the other two species. The analysis of the available literature on the three species indicated a general lack of comparable information on their elemental composition. The need to implement extended elemental fingerprinting techniques for shellfish quality assessment is discussed, in view of other complementary profiling methods such as NMR-based metabolomics.

  19. Borna disease virus infection perturbs energy metabolites and amino acids in cultured human oligodendroglia cells.

    Directory of Open Access Journals (Sweden)

    Rongzhong Huang

    Full Text Available BACKGROUND: Borna disease virus is a neurotropic, non-cytolytic virus that has been widely employed in neuroscientific research. Previous studies have revealed that metabolic perturbations are associated with Borna disease viral infection. However, the pathophysiological mechanism underlying its mode of action remains unclear. METHODOLOGY: Human oligodendroglia cells infected with the human strain Borna disease virus Hu-H1 and non-infected matched control cells were cultured in vitro. At day 14 post-infection, a proton nuclear magnetic resonance-based metabonomic approach was used to differentiate the metabonomic profiles of 28 independent intracellular samples from Borna disease virus-infected cells (n = 14 and matched control cells (n = 14. Partial least squares discriminant analysis was performed to demonstrate that the whole metabonomic patterns enabled discrimination between the two groups, and further statistical testing was applied to determine which individual metabolites displayed significant differences between the two groups. FINDINGS: Metabonomic profiling revealed perturbations in 23 metabolites, 19 of which were deemed individually significant: nine energy metabolites (α-glucose, acetate, choline, creatine, formate, myo-inositol, nicotinamide adenine dinucleotide, pyruvate, succinate and ten amino acids (aspartate, glutamate, glutamine, glycine, histidine, isoleucine, phenylalanine, threonine, tyrosine, valine. Partial least squares discriminant analysis demonstrated that the whole metabolic patterns enabled statistical discrimination between the two groups. CONCLUSION: Borna disease viral infection perturbs the metabonomic profiles of several metabolites in human oligodendroglia cells cultured in vitro. The findings suggest that Borna disease virus manipulates the host cell's metabolic network to support viral replication and proliferation.

  20. The influence of different diets on metabolism and atherosclerosis processes-A porcine model: Blood serum, urine and tissues 1H NMR metabolomics targeted analysis.

    Directory of Open Access Journals (Sweden)

    Adam Zabek

    Full Text Available The global epidemic of cardiovascular diseases leads to increased morbidity and mortality caused mainly by myocardial infarction and stroke. Atherosclerosis is the major pathological process behind this epidemic. We designed a novel model of atherosclerosis in swine. Briefly, the first group (11 pigs received normal pig feed (balanced diet group-BDG for 12 months, the second group (9 pigs was fed a Western high-calorie diet (unbalanced diet group-UDG for 12 months, the third group (8 pigs received a Western type high-calorie diet for 9 months later replaced by a normal diet for 3 months (regression group-RG. Clinical measurements included zoometric data, arterial blood pressure, heart rate and ultrasonographic evaluation of femoral arteries. Then, the animals were sacrificed and the blood serum, urine and skeletal muscle tissue were collected and 1H NMR based metabolomics studies with the application of fingerprinting PLS-DA and univariate analysis were done. Our results have shown that the molecular disturbances might overlap with other diseases such as onset of diabetes, sleep apnea and other obesity accompanied diseases. Moreover, we revealed that once initiated, molecular changes did not return to homeostatic equilibrium, at least for the duration of this experiment.

  1. The influence of different diets on metabolism and atherosclerosis processes—A porcine model: Blood serum, urine and tissues 1H NMR metabolomics targeted analysis

    Science.gov (United States)

    Paslawska, Urszula; Wojtowicz, Wojciech; Drozdz, Katarzyna; Polakof, Sergio; Podhorska, Marzena; Dziegiel, Piotr; Szuba, Andrzej

    2017-01-01

    The global epidemic of cardiovascular diseases leads to increased morbidity and mortality caused mainly by myocardial infarction and stroke. Atherosclerosis is the major pathological process behind this epidemic. We designed a novel model of atherosclerosis in swine. Briefly, the first group (11 pigs) received normal pig feed (balanced diet group—BDG) for 12 months, the second group (9 pigs) was fed a Western high-calorie diet (unbalanced diet group—UDG) for 12 months, the third group (8 pigs) received a Western type high-calorie diet for 9 months later replaced by a normal diet for 3 months (regression group—RG). Clinical measurements included zoometric data, arterial blood pressure, heart rate and ultrasonographic evaluation of femoral arteries. Then, the animals were sacrificed and the blood serum, urine and skeletal muscle tissue were collected and 1H NMR based metabolomics studies with the application of fingerprinting PLS-DA and univariate analysis were done. Our results have shown that the molecular disturbances might overlap with other diseases such as onset of diabetes, sleep apnea and other obesity accompanied diseases. Moreover, we revealed that once initiated, molecular changes did not return to homeostatic equilibrium, at least for the duration of this experiment. PMID:28991897

  2. Structural analysis of the interleukin-8/glycosaminoglycan interactions by amide hydrogen/deuterium exchange mass spectrometry.

    Science.gov (United States)

    Hofmann, Tommy; Samsonov, Sergey A; Pichert, Annelie; Lemmnitzer, Katharina; Schiller, Jürgen; Huster, Daniel; Pisabarro, M Teresa; von Bergen, Martin; Kalkhof, Stefan

    2015-11-01

    The recruitment of different chemokines and growth factors by glycosaminoglycans (GAGs) such as chondroitin sulfate or hyaluronan plays a critical role in wound healing processes. Thus, there is a special interest in the design of artificial extracellular matrices with improved properties concerning GAG interaction with common regulating proteins. In this study, amide hydrogen/deuterium (H/D) exchange mass spectrometry (HDX MS) combined with molecular modeling and docking experiments was used to obtain structural models of proinflammatory chemokine interleukin-8 (IL-8) in complex with hexameric chondroitin sulfate. Experiments on the intact protein showed a difference in deuterium labeling of IL-8 due to chondroitin sulfate binding. The extent of deuteration was reduced from 24% to 13% after 2 min exchange time, which corresponds to a reduced exchange of approximately 10 backbone amides. By local HDX MS experiments, H/D exchange information on the complete sequence of IL-8 could be obtained. A significantly reduced H/D exchange, especially of the C-terminal α-helical region comprising amino acids 70-77 and to the loop comprising amino acids 27-29 was observed in the presence of chondroitin sulfate. HDX MS data were used to model the IL-8/chondroitin sulfate complex. The binding interface of IL-8 and chondroitin sulfate determined this way correlated excellently with the corresponding NMR based atomistic model previously published. Our results demonstrate that HDX-MS in combination with molecular modeling is a valuable approach for the analysis of protein/GAG complexes at physiological pH, temperature, and salt concentration. The fact that HDX-MS requires only micrograms of protein and GAGs makes it a very promising technique to address protein-GAG interactions. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Decision analysis multicriteria analysis

    International Nuclear Information System (INIS)

    Lombard, J.

    1986-09-01

    The ALARA procedure covers a wide range of decisions from the simplest to the most complex one. For the simplest one the engineering judgement is generally enough and the use of a decision aiding technique is therefore not necessary. For some decisions the comparison of the available protection option may be performed from two or a few criteria (or attributes) (protection cost, collective dose,...) and the use of rather simple decision aiding techniques, like the Cost Effectiveness Analysis or the Cost Benefit Analysis, is quite enough. For the more complex decisions, involving numerous criteria or for decisions involving large uncertainties or qualitative judgement the use of these techniques, even the extended cost benefit analysis, is not recommended and appropriate techniques like multi-attribute decision aiding techniques are more relevant. There is a lot of such particular techniques and it is not possible to present all of them. Therefore only two broad categories of multi-attribute decision aiding techniques will be presented here: decision analysis and the outranking analysis

  4. Evaluation of standard and advanced preprocessing methods for the univariate analysis of blood serum 1H-NMR spectra.

    Science.gov (United States)

    De Meyer, Tim; Sinnaeve, Davy; Van Gasse, Bjorn; Rietzschel, Ernst-R; De Buyzere, Marc L; Langlois, Michel R; Bekaert, Sofie; Martins, José C; Van Criekinge, Wim

    2010-10-01

    Proton nuclear magnetic resonance ((1)H-NMR)-based metabolomics enables the high-resolution and high-throughput assessment of a broad spectrum of metabolites in biofluids. Despite the straightforward character of the experimental methodology, the analysis of spectral profiles is rather complex, particularly due to the requirement of numerous data preprocessing steps. Here, we evaluate how several of the most common preprocessing procedures affect the subsequent univariate analyses of blood serum spectra, with a particular focus on how the standard methods perform compared to more advanced examples. Carr-Purcell-Meiboom-Gill 1D (1)H spectra were obtained for 240 serum samples from healthy subjects of the Asklepios study. We studied the impact of different preprocessing steps--integral (standard method) and probabilistic quotient normalization; no, equidistant (standard), and adaptive-intelligent binning; mean (standard) and maximum bin intensity data summation--on the resonance intensities of three different types of metabolites: triglycerides, glucose, and creatinine. The effects were evaluated by correlating the differently preprocessed NMR data with the independently measured metabolite concentrations. The analyses revealed that the standard methods performed inferiorly and that a combination of probabilistic quotient normalization after adaptive-intelligent binning and maximum intensity variable definition yielded the best overall results (triglycerides, R = 0.98; glucose, R = 0.76; creatinine, R = 0.70). Therefore, at least in the case of serum metabolomics, these or equivalent methods should be preferred above the standard preprocessing methods, particularly for univariate analyses. Additional optimization of the normalization procedure might further improve the analyses.

  5. Metabolomic analysis of anti-hypoxia and anti-anxiety effects of Fu Fang Jin Jing Oral Liquid.

    Directory of Open Access Journals (Sweden)

    Xia Liu

    Full Text Available BACKGROUND: Herba Rhodiolae is a traditional Chinese medicine used by the Tibetan people for treating hypoxia related diseases such as anxiety. Based on the previous work, we developed and patented an anti-anxiety herbal formula Fu Fang Jin Jing Oral Liquid (FJJOL with Herba Rhodiolae as a chief ingredient. In this study, the anti-hypoxia and anti-anxiety effects of FJJOL in a high altitude forced-swimming mouse model with anxiety symptoms will be elucidated by NMR-based metabolomics. METHODS: In our experiments, the mice were divided randomly into four groups as flatland group, high altitude saline-treated group, high altitude FJJOL-treated group, and high altitude diazepam-treated group. To cause anxiety effects and hypoxic defects, a combination use of oxygen level decreasing (hypobaric cabin and oxygen consumption increasing (exhaustive swimming were applied to mice. After a three-day experimental handling, aqueous metabolites of mouse brain tissues were extracted and then subjected to NMR analysis. The therapeutic effects of FJJOL on the hypobaric hypoxia mice with anxiety symptoms were verified. RESULTS: Upon hypoxic exposure, both energy metabolism defects and disorders of functional metabolites in brain tissues of mice were observed. PCA, PLS-DA and OPLS-DA scatter plots revealed a clear group clustering for metabolic profiles in the hypoxia versus normoxia samples. After a three-day treatment with FJJOL, significant rescue effects on energy metabolism were detected, and levels of ATP, fumarate, malate and lactate in brain tissues of hypoxic mice recovered. Meanwhile, FJJOL also up-regulated the neurotransmitter GABA, and the improvement of anxiety symptoms was highly related to this effect. CONCLUSIONS: FJJOL ameliorated hypobaric hypoxia effects by regulating energy metabolism, choline metabolism, and improving the symptoms of anxiety. The anti-anxiety therapeutic effects of FJJOL were comparable to the conventional anti-anxiety drug

  6. Comparison of earthworm responses to petroleum hydrocarbon exposure in aged field contaminated soil using traditional ecotoxicity endpoints and 1H NMR-based metabolomics

    International Nuclear Information System (INIS)

    Whitfield Åslund, Melissa; Stephenson, Gladys L.; Simpson, André J.; Simpson, Myrna J.

    2013-01-01

    1 H NMR metabolomics and conventional ecotoxicity endpoints were used to examine the response of earthworms exposed to petroleum hydrocarbons (PHCs) in soil samples collected from a site that was contaminated with crude oil from a pipeline failure in the mid-1990s. The conventional ecotoxicity tests showed that the soils were not acutely toxic to earthworms (average survival ≥90%), but some soil samples impaired reproduction endpoints by >50% compared to the field control soil. Additionally, metabolomics revealed significant relationships between earthworm metabolic profiles (collected after 2 or 14 days of exposure) and soil properties including soil PHC concentration. Further comparisons by partial least squares regression revealed a significant relationship between the earthworm metabolomic data (collected after only 2 or 14 days) and the reproduction endpoints (measured after 63 days). Therefore, metabolomic responses measured after short exposure periods may be predictive of chronic, ecologically relevant toxicity endpoints for earthworms exposed to soil contaminants. -- Highlights: •Earthworm response to petroleum hydrocarbon exposure in soil is examined. •Metabolomics shows significant changes to metabolic profile after 2 days. •Significant relationships observed between metabolomic and reproduction endpoints. •Metabolomics may have value as a rapid screening tool for chronic toxicity. -- Earthworm metabolomic responses measured after 2 and 14 days are compared to traditional earthworm ecotoxicity endpoints (survival and reproduction) in petroleum hydrocarbon contaminated soil

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

    Science.gov (United States)

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

    2016-02-17

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

  8. 1H NMR-Based Metabolomics Study of the Toxicological Effects in Rats Induced by ?Renqing Mangjue? Pill, a Traditional Tibetan Medicine

    OpenAIRE

    Xu, Can; Rezeng, Caidan; Li, Jian; Zhang, Lan; Yan, Yujing; Gao, Jian; Wang, Yingfeng; Li, Zhongfeng; Chen, Jianxin

    2017-01-01

    “RenqingMangjue” pill (RMP), as an effective prescription of Traditional Tibetan Medicine (TTM), has been widely used in treating digestive diseases and ulcerative colitis for over a thousand years. In certain classical Tibetan Medicine, heavy metal may add as an active ingredient, but it may cause contamination unintentionally in some cases. Therefore, the toxicity and adverse effects of TTM became to draw public attention. In this study, 48 male Wistar rats were orally administrated with di...

  9. Target Immobilization as a Strategy for NMR-Based Fragment Screening: Comparison of TINS, STD, and SPR for Fragment Hit Identification

    NARCIS (Netherlands)

    Kobayashi, M.; Retra, K.; Figaroa, F.; Hollander, J.G.; Ab, E.; Heetebrij, R.J.; Irth, H.; Siegal, G.

    2010-01-01

    Fragment-based drug discovery (FBDD) has become a widely accepted tool that is complementary to high-throughput screening (HTS) in developing small-molecule inhibitors of pharmaceutical targets. Because a fragment campaign can only be as successful as the hit matter found, it is critical that the

  10. NMR-based modelling and binding studies of a ternary complex between chicken liver bile acid binding protein and bile acids

    NARCIS (Netherlands)

    Tomasell, S.; Ragona, L.; Zetta, L.; Assfalg, M.; Ferranti, P.; Longhi, R.; Bonvin, A.M.J.J.; Molinari, H.

    2007-01-01

    Chicken liver bile acid binding protein (cL-BABP) is involved in bile acid transport in the liver cytosol. A detailed study of the mechanism of binding and selectivity of bile acids binding proteins towards the physiological pool of bile salts is a key issue for the complete understanding of the

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    The plasma and urine metabolome of 192 overweight 12-15-year-old adolescents (BMI of 25.4 ± 2.3 kg/m(2)) were examined in order to elucidate gender, pubertal development measured as Tanner stage, physical activity measured as number of steps taken daily, and intra-/interindividual differences...... in the metabolome are being commenced already in childhood. The relationship between Tanner stage and the metabolome showed that pubertal development stage was positively related to urinary creatinine excretion and negatively related to urinary citrate content. No relations between physical activity...... and life-style related diseases. While this study is preliminary, these results may have the potential to translate into clinical applicability upon further investigations; if biomarkers for Tanner stage can be established, these might be used for identification of individuals susceptible to an early...

  12. Proton NMR based serum metabolic profile correlates with the neurological recovery in treated acute spinal cord injury (ASCI) subjects: A pilot study.

    Science.gov (United States)

    Singh, Alka; Srivastava, Rajeshwar Nath; Agrahari, Ashok; Singh, Suruchi; Raj, Saloni; Chatterji, Tanushri; Mahdi, Abbas Ali; Garg, Ravindra Kumar; Roy, Raja

    2018-05-01

    Acute Spinal Cord Injury (ASCI) is still having substantial morbidity and mortality despite of advanced therapeutics. Major obstacles are paucity of monitoring tools or biomarkers for severity determination, recovery and prognostication. A prospective case control pilot study with serum 1 H NMR spectroscopic metabolic profiling was carried out to evaluate metabolites perturbations and its relationship with recovery and to see role of stem cells in facilitating neurological recovery. Twenty subjects with ASCI were classified on the basis of therapeutic modality into surgical fixation alone (Group-1, n = 10), stem cell adjuvant (Group-2, n = 10) and healthy controls (Group-0, n = 10). Serum samples were collected at admission (baseline) and after six months (follow-up). NMR data of serum sample were quantified and subjected to Wilcoxon and ANOVA tests. Further validation was performed using supervised OSC-PCA and OPLS-DA by incorporating substantial control samples. Twenty-eight metabolites were identified; well resolved resonances of fifteen metabolites were quantified wherein seven were statistically significant. Predominantly amino acids and ketone bodies played vital role in the differentiation of groups. Serum NMR spectroscopy reveals certain metabolites perturbations having clear correlation with pattern of recovery in treated ASCI subject. Stem cells treatment group had comparatively effective recovery. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Multi-conformer molecules in solutions: an NMR-based DFT/MP2 conformational study of two glucopyranosides of a vitamin E model compound.

    Science.gov (United States)

    Nazarski, Ryszard B; Wałejko, Piotr; Witkowski, Stanisław

    2016-03-21

    Overall conformations of both anomeric per-O-acetylated glucosyl derivatives of 2,2,5,7,8-pentamethylchroman-6-ol were studied in the context of their high flexibility, on the basis of NMR spectra in CDCl3 solution and related DFT calculation results. A few computational protocols were used, including diverse density functional/basis set combinations with a special emphasis on accounting (at various steps of the study) for the impact of intramolecular London-dispersion (LD) effects on geometries and relative Gibbs free energies (ΔGs) of different conformers coexisting in solution. The solvent effect was simulated by an IEF-PCM approach with the UFF radii; its other variants, including the use of the recently introduced IDSCRF radii, were employed for a few compact B3LYP-GD3BJ optimized structures showing one small imaginary vibrational frequency. The advantage of using IDSCRF radii for such purposes was shown. Of the four tested DFT methods, only the application of the B3LYP/6-31+G(d,p) approximation afforded ensembles of 7-8 single forms for which population-average values of computed NMR parameters (δH, δC and some (n)JHH data) were in close agreement with those measured experimentally; binuclear (δH,C 1 : 1) correlations, rH,C(2) = 0.9998. The associated individual ΔG values, corrected for LD interactions by applying Grimme's DFT-D3 terms, afforded relative contents of different contributors to the analyzed conformational families in much better agreement with pertinent DFT/NMR-derived populations (i.e., both data sets were found to be practically equal within the limits of estimated errors) than those calculated from dispersion uncorrected ΔGs. All these main findings were confirmed by additional results obtained at the MP2 level of theory. Various other aspects of the study such as the crystal vs. solution structure, gg/gt rotamer ratio, diagnostic (de)shielding effects, dihydrogen C-H···H-C contacts, and doubtful applicability of some specialized DFT functionals (M06-2X, ωB97X-D and B3LYP-GD3BJ) for the description of highly flexible molecules are also discussed in detail.

  14. Performance analysis

    International Nuclear Information System (INIS)

    2008-05-01

    This book introduces energy and resource technology development business with performance analysis, which has business division and definition, analysis of current situation of support, substance of basic plan of national energy, resource technique development, selection of analysis index, result of performance analysis by index, performance result of investigation, analysis and appraisal of energy and resource technology development business in 2007.

  15. New insight into the microtexture of chalks from NMR analysis

    DEFF Research Database (Denmark)

    Faÿ-Gomord, Ophélie; Soete, Jeroen; Katika, Konstantina

    2016-01-01

    An integrated petrographical and petrophysical study was carried out on a set of 35 outcrop chalk samples, covering a wide range of lithologies and textures. In this study various chalk rock-types have been characterized, in terms of microtextures and porous network, by integrating both geological...... quality chalks independently of their sedimentological and/or diagenetic history. The study aims to develop an NMR-based approach to characterize a broad range of chalk samples. The provided laboratory low-field NMR chalk classification can be used as a guide to interpret NMR logging data...

  16. Instrumental analysis

    International Nuclear Information System (INIS)

    Kim, Seung Jae; Seo, Seong Gyu

    1995-03-01

    This textbook deals with instrumental analysis, which consists of nine chapters. It has Introduction of analysis chemistry, the process of analysis and types and form of the analysis, Electrochemistry on basic theory, potentiometry and conductometry, electromagnetic radiant rays and optical components on introduction and application, Ultraviolet rays and Visible spectrophotometry, Atomic absorption spectrophotometry on introduction, flame emission spectrometry and plasma emission spectrometry. The others like infrared spectrophotometry, X-rays spectrophotometry and mass spectrometry, chromatography and the other instrumental analysis like radiochemistry.

  17. Urinary Metabolic Phenotyping Reveals Differences in the Metabolic Status of Healthy and Inflammatory Bowel Disease (IBD Children in Relation to Growth and Disease Activity

    Directory of Open Access Journals (Sweden)

    Francois-Pierre Martin

    2016-08-01

    Full Text Available Background: Growth failure and delayed puberty are well known features of children and adolescents with inflammatory bowel disease (IBD, in addition to the chronic course of the disease. Urinary metabonomics was applied in order to better understand metabolic changes between healthy and IBD children. Methods: 21 Pediatric patients with IBD (mean age 14.8 years, 8 males were enrolled from the Pediatric Gastroenterology Outpatient Clinic over two years. Clinical and biological data were collected at baseline, 6, and 12 months. 27 healthy children (mean age 12.9 years, 16 males were assessed at baseline. Urine samples were collected at each visit and subjected to 1H Nuclear Magnetic Resonance (NMR spectroscopy. Results: Using 1H NMR metabonomics, we determined that urine metabolic profiles of IBD children differ significantly from healthy controls. Metabolic differences include central energy metabolism, amino acid, and gut microbial metabolic pathways. The analysis described that combined urinary urea and phenylacetylglutamine—two readouts of nitrogen metabolism—may be relevant to monitor metabolic status in the course of disease. Conclusion: Non-invasive sampling of urine followed by metabonomic profiling can elucidate and monitor the metabolic status of children in relation to disease status. Further developments of omic-approaches in pediatric research might deliver novel nutritional and metabolic hypotheses.

  18. Content Analysis

    Directory of Open Access Journals (Sweden)

    George Bedinelli Rossi

    2014-09-01

    Full Text Available This study introduces the various definitions and types of content analysis. This type of analysis historically presents itself as a quantitative approach to data analysis and currently shows up as a qualitative approach. The most common types are the conceptual and relational analysis. The latter receives influences of linguistic, cognitive and mental models and it is subdivided in affective extraction, analysis of proximity and cognitive mapping. Regarding the importance of this type of analysis, we have quantitative and qualitative character and the latter approach can be used to identify hypotheses, theoretical constructs or even models that can be tested by multivariate statistical techniques or even by experiments. 

  19. Sensitivity analysis

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003741.htm Sensitivity analysis To use the sharing features on this page, please enable JavaScript. Sensitivity analysis determines the effectiveness of antibiotics against microorganisms (germs) ...

  20. Real analysis

    CERN Document Server

    McShane, Edward James

    2013-01-01

    This text surveys practical elements of real function theory, general topology, and functional analysis. Discusses the maximality principle, the notion of convergence, the Lebesgue-Stieltjes integral, function spaces and harmonic analysis. Includes exercises. 1959 edition.

  1. Strategic analysis

    OpenAIRE

    Bartuňková, Alena

    2011-01-01

    The goal of the master thesis is to conduct a strategic analysis of the Czech Export Bank. The work is divided in two parts, a theoretically methodological and practical part. Within theoretical part there is identified strategy by different approaches and there are described the procedures for strategic analysis. Findings from the theoretically methodological part are applied in the practical part and subsequently are used in the strategic analysis. The external analysis is characterized by ...

  2. Fourier analysis

    CERN Document Server

    Stade, Eric

    2005-01-01

    A reader-friendly, systematic introduction to Fourier analysis Rich in both theory and application, Fourier Analysis presents a unique and thorough approach to a key topic in advanced calculus. This pioneering resource tells the full story of Fourier analysis, including its history and its impact on the development of modern mathematical analysis, and also discusses essential concepts and today's applications. Written at a rigorous level, yet in an engaging style that does not dilute the material, Fourier Analysis brings two profound aspects of the discipline to the forefront: the wealth of ap

  3. Functional analysis

    CERN Document Server

    Kantorovich, L V

    1982-01-01

    Functional Analysis examines trends in functional analysis as a mathematical discipline and the ever-increasing role played by its techniques in applications. The theory of topological vector spaces is emphasized, along with the applications of functional analysis to applied analysis. Some topics of functional analysis connected with applications to mathematical economics and control theory are also discussed. Comprised of 18 chapters, this book begins with an introduction to the elements of the theory of topological spaces, the theory of metric spaces, and the theory of abstract measure space

  4. Dimensional Analysis

    Indian Academy of Sciences (India)

    Dimensional analysis is a useful tool which finds important applications in physics and engineering. It is most effective when there exist a maximal number of dimensionless quantities constructed out of the relevant physical variables. Though a complete theory of dimen- sional analysis was developed way back in 1914 in a.

  5. Applied analysis

    CERN Document Server

    Lanczos, Cornelius

    1956-01-01

    Basic text for graduate and advanced undergraduate deals with search for roots of algebraic equations encountered in vibration and flutter problems and in those of static and dynamic stability. Other topics devoted to matrices and eigenvalue problems, large-scale linear systems, harmonic analysis and data analysis, more.

  6. Incidents analysis

    International Nuclear Information System (INIS)

    Francois, P.

    1996-01-01

    We undertook a study programme at the end of 1991. To start with, we performed some exploratory studies aimed at learning some preliminary lessons on this type of analysis: Assessment of the interest of probabilistic incident analysis; possibility of using PSA scenarios; skills and resources required. At the same time, EPN created a working group whose assignment was to define a new approach for analysis of incidents on NPPs. This working group gave thought to both aspects of Operating Feedback that EPN wished to improve: Analysis of significant incidents; analysis of potential consequences. We took part in the work of this group, and for the second aspects, we proposed a method based on an adaptation of the event-tree method in order to establish a link between existing PSA models and actual incidents. Since PSA provides an exhaustive database of accident scenarios applicable to the two most common types of units in France, they are obviously of interest for this sort of analysis. With this method we performed some incident analyses, and at the same time explores some methods employed abroad, particularly ASP (Accident Sequence Precursor, a method used by the NRC). Early in 1994 EDF began a systematic analysis programme. The first, transient phase will set up methods and an organizational structure. 7 figs

  7. Factor Analysis via Components Analysis

    Science.gov (United States)

    Bentler, Peter M.; de Leeuw, Jan

    2011-01-01

    When the factor analysis model holds, component loadings are linear combinations of factor loadings, and vice versa. This interrelation permits us to define new optimization criteria and estimation methods for exploratory factor analysis. Although this article is primarily conceptual in nature, an illustrative example and a small simulation show…

  8. Dimensional Analysis

    CERN Document Server

    Tan, Qingming

    2011-01-01

    Dimensional analysis is an essential scientific method and a powerful tool for solving problems in physics and engineering. This book starts by introducing the Pi Theorem, which is the theoretical foundation of dimensional analysis. It also provides ample and detailed examples of how dimensional analysis is applied to solving problems in various branches of mechanics. The book covers the extensive findings on explosion mechanics and impact dynamics contributed by the author's research group over the past forty years at the Chinese Academy of Sciences. The book is intended for advanced undergra

  9. Recursive analysis

    CERN Document Server

    Goodstein, R L

    2010-01-01

    Recursive analysis develops natural number computations into a framework appropriate for real numbers. This text is based upon primary recursive arithmetic and presents a unique combination of classical analysis and intuitional analysis. Written by a master in the field, it is suitable for graduate students of mathematics and computer science and can be read without a detailed knowledge of recursive arithmetic.Introductory chapters on recursive convergence and recursive and relative continuity are succeeded by explorations of recursive and relative differentiability, the relative integral, and

  10. Hydroeconomic analysis

    DEFF Research Database (Denmark)

    Bauer-Gottwein, Peter; Riegels, Niels; Pulido-Velazquez, Manuel

    2017-01-01

    Hydroeconomic analysis and modeling provides a consistent and quantitative framework to assess the links between water resources systems and economic activities related to water use, simultaneously modeling water supply and water demand. It supports water managers and decision makers in assessing...... trade-offs between different water uses, different geographic regions, and various economic sectors and between the present and the future. Hydroeconomic analysis provides consistent economic performance criteria for infrastructure development and institutional reform in water policies and management...... organizations. This chapter presents an introduction to hydroeconomic analysis and modeling, and reviews the state of the art in the field. We review available economic water-valuation techniques and summarize the main types of decision problems encountered in hydroeconomic analysis. Popular solution strategies...

  11. Biorefinery Analysis

    Energy Technology Data Exchange (ETDEWEB)

    2016-06-01

    Fact sheet summarizing NREL's techno-economic analysis and life-cycle assessment capabilities to connect research with future commercial process integration, a critical step in the scale-up of biomass conversion technologies.

  12. Nonlinear analysis

    CERN Document Server

    Gasinski, Leszek

    2005-01-01

    Hausdorff Measures and Capacity. Lebesgue-Bochner and Sobolev Spaces. Nonlinear Operators and Young Measures. Smooth and Nonsmooth Analysis and Variational Principles. Critical Point Theory. Eigenvalue Problems and Maximum Principles. Fixed Point Theory.

  13. Analysis II

    CERN Document Server

    Tao, Terence

    2016-01-01

    This is part two of a two-volume book on real analysis and is intended for senior undergraduate students of mathematics who have already been exposed to calculus. The emphasis is on rigour and foundations of analysis. Beginning with the construction of the number systems and set theory, the book discusses the basics of analysis (limits, series, continuity, differentiation, Riemann integration), through to power series, several variable calculus and Fourier analysis, and then finally the Lebesgue integral. These are almost entirely set in the concrete setting of the real line and Euclidean spaces, although there is some material on abstract metric and topological spaces. The book also has appendices on mathematical logic and the decimal system. The entire text (omitting some less central topics) can be taught in two quarters of 25–30 lectures each. The course material is deeply intertwined with the exercises, as it is intended that the student actively learn the material (and practice thinking and writing ri...

  14. Analysis I

    CERN Document Server

    Tao, Terence

    2016-01-01

    This is part one of a two-volume book on real analysis and is intended for senior undergraduate students of mathematics who have already been exposed to calculus. The emphasis is on rigour and foundations of analysis. Beginning with the construction of the number systems and set theory, the book discusses the basics of analysis (limits, series, continuity, differentiation, Riemann integration), through to power series, several variable calculus and Fourier analysis, and then finally the Lebesgue integral. These are almost entirely set in the concrete setting of the real line and Euclidean spaces, although there is some material on abstract metric and topological spaces. The book also has appendices on mathematical logic and the decimal system. The entire text (omitting some less central topics) can be taught in two quarters of 25–30 lectures each. The course material is deeply intertwined with the exercises, as it is intended that the student actively learn the material (and practice thinking and writing ri...

  15. Water analysis

    International Nuclear Information System (INIS)

    Fishman, M.J.; Erdmann, D.E.

    1975-01-01

    The literature of analytical chemistry applied to water analysis is reviewed for the period Oct. 1972, through Sept. 1974. The material used in preparing the review comes mainly from major analytical journals and Chemical Abstracts. Many methods, including activation and radiometric, are discussed for the analyses of various elements, including Mo, U, Th, rare earths, and halides. Radioactivity and isotope analysis are also discussed. (663 references.) (U.S.)

  16. Link Analysis

    Science.gov (United States)

    Donoho, Steve

    Link analysis is a collection of techniques that operate on data that can be represented as nodes and links. This chapter surveys a variety of techniques including subgraph matching, finding cliques and K-plexes, maximizing spread of influence, visualization, finding hubs and authorities, and combining with traditional techniques (classification, clustering, etc). It also surveys applications including social network analysis, viral marketing, Internet search, fraud detection, and crime prevention.

  17. Radioactivation analysis

    International Nuclear Information System (INIS)

    1959-01-01

    Radioactivation analysis is the technique of radioactivation analysis of the constituents of a very small sample of matter by making the sample artificially radioactive. The first stage is to make the sample radioactive by artificial means, e.g. subject it to neutron bombardment. Once the sample has been activated, or made radioactive, the next task is to analyze the radiations given off by the sample. This analysis would indicate the nature and quantities of the various elements present in the sample. The reason is that the radiation from a particular radioisotope. In 1959 a symposium on 'Radioactivation Analysis' was organized in Vienna by the IAEA and the Joint Commission on Applied Radioactivity (ICSU). It was pointed out that there are certain factors creating uncertainties and elaborated how to overcome them. Attention was drawn to the fact that radioactivation analysis had proven a powerful tool tackling fundamental problems in geo- and cosmochemistry, and a review was given of the recent work in this field. Because of its extreme sensitivity radioactivation analysis had been principally employed for trace detection and its most extensive use has been in control of semiconductors and very pure metals. An account of the experience gained in the USA was given, where radioactivation analysis was being used by many investigators in various scientific fields as a practical and useful tool for elemental analyses. Much of this work had been concerned with determining sub microgramme and microgramme concentration of many different elements in samples of biological materials, drugs, fertilizers, fine chemicals, foods, fuels, glass, ceramic materials, metals, minerals, paints, petroleum products, resinous materials, soils, toxicants, water and other materials. In addition to these studies, radioactivation analysis had been used by other investigators to determine isotopic ratios of the stable isotopes of some of the elements. Another paper dealt with radioactivation

  18. Real analysis

    CERN Document Server

    Loeb, Peter A

    2016-01-01

    This textbook is designed for a year-long course in real analysis taken by beginning graduate and advanced undergraduate students in mathematics and other areas such as statistics, engineering, and economics. Written by one of the leading scholars in the field, it elegantly explores the core concepts in real analysis and introduces new, accessible methods for both students and instructors. The first half of the book develops both Lebesgue measure and, with essentially no additional work for the student, general Borel measures for the real line. Notation indicates when a result holds only for Lebesgue measure. Differentiation and absolute continuity are presented using a local maximal function, resulting in an exposition that is both simpler and more general than the traditional approach. The second half deals with general measures and functional analysis, including Hilbert spaces, Fourier series, and the Riesz representation theorem for positive linear functionals on continuous functions with compact support....

  19. Numerical analysis

    CERN Document Server

    Rao, G Shanker

    2006-01-01

    About the Book: This book provides an introduction to Numerical Analysis for the students of Mathematics and Engineering. The book is designed in accordance with the common core syllabus of Numerical Analysis of Universities of Andhra Pradesh and also the syllabus prescribed in most of the Indian Universities. Salient features: Approximate and Numerical Solutions of Algebraic and Transcendental Equation Interpolation of Functions Numerical Differentiation and Integration and Numerical Solution of Ordinary Differential Equations The last three chapters deal with Curve Fitting, Eigen Values and Eigen Vectors of a Matrix and Regression Analysis. Each chapter is supplemented with a number of worked-out examples as well as number of problems to be solved by the students. This would help in the better understanding of the subject. Contents: Errors Solution of Algebraic and Transcendental Equations Finite Differences Interpolation with Equal Intervals Interpolation with Unequal Int...

  20. Real analysis

    CERN Document Server

    DiBenedetto, Emmanuele

    2016-01-01

    The second edition of this classic textbook presents a rigorous and self-contained introduction to real analysis with the goal of providing a solid foundation for future coursework and research in applied mathematics. Written in a clear and concise style, it covers all of the necessary subjects as well as those often absent from standard introductory texts. Each chapter features a “Problems and Complements” section that includes additional material that briefly expands on certain topics within the chapter and numerous exercises for practicing the key concepts. The first eight chapters explore all of the basic topics for training in real analysis, beginning with a review of countable sets before moving on to detailed discussions of measure theory, Lebesgue integration, Banach spaces, functional analysis, and weakly differentiable functions. More topical applications are discussed in the remaining chapters, such as maximal functions, functions of bounded mean oscillation, rearrangements, potential theory, a...

  1. Numerical analysis

    CERN Document Server

    Jacques, Ian

    1987-01-01

    This book is primarily intended for undergraduates in mathematics, the physical sciences and engineering. It introduces students to most of the techniques forming the core component of courses in numerical analysis. The text is divided into eight chapters which are largely self-contained. However, with a subject as intricately woven as mathematics, there is inevitably some interdependence between them. The level of difficulty varies and, although emphasis is firmly placed on the methods themselves rather than their analysis, we have not hesitated to include theoretical material when we consider it to be sufficiently interesting. However, it should be possible to omit those parts that do seem daunting while still being able to follow the worked examples and to tackle the exercises accompanying each section. Familiarity with the basic results of analysis and linear algebra is assumed since these are normally taught in first courses on mathematical methods. For reference purposes a list of theorems used in the t...

  2. Numerical analysis

    CERN Document Server

    Scott, L Ridgway

    2011-01-01

    Computational science is fundamentally changing how technological questions are addressed. The design of aircraft, automobiles, and even racing sailboats is now done by computational simulation. The mathematical foundation of this new approach is numerical analysis, which studies algorithms for computing expressions defined with real numbers. Emphasizing the theory behind the computation, this book provides a rigorous and self-contained introduction to numerical analysis and presents the advanced mathematics that underpin industrial software, including complete details that are missing from most textbooks. Using an inquiry-based learning approach, Numerical Analysis is written in a narrative style, provides historical background, and includes many of the proofs and technical details in exercises. Students will be able to go beyond an elementary understanding of numerical simulation and develop deep insights into the foundations of the subject. They will no longer have to accept the mathematical gaps that ex...

  3. META - ANALYSIS

    Directory of Open Access Journals (Sweden)

    Ivana Ilić

    2009-04-01

    Full Text Available Meta-analysis is a statistical and analytical method which combines and synthesizes different independent studies and integrates their results into a common result. In the past few years, there has been an increasing interest in meta-analysis from both medical researches and statisticians. One of the main targets of clinical research is to obtain reliable results, although clinical trials with the same topic often give contrasting results. Medical practice is strongly influenced by the results of clinical studies if they are brought to light through important scientific journals. This large amount of information often contains scattered data, and discordant conclusions, and sometimes it is very hard to define the quality and validity of each study. Today, a large number of biomedical journals give importance to articles using meta-analysis in their researches. By using meta-analysis as a method of summarizing, integrating and analyzing a large number of independent studies on the same topic and finally pooling their results into a common result, a researcher can achieve relevant, objective and unbiased conclusions, if the procedure is well-conducted and controlled by the experts. The aim of this paper is to provide the clinical researcher with the basic principles of meta-analysis and its concepts in order to perform a valid clinical study and to report results in the correct way. In today’s evidence-based medical practice, it is crucial for anyone who wants to deal seriously with the scientific work in the biomedical field to learn mathematical and statistical principles that build meta-analysis. In that way, this statistical method could be of great importance to the researcher who wants to respond to new demands of modern medical science.

  4. Outlier analysis

    CERN Document Server

    Aggarwal, Charu C

    2013-01-01

    With the increasing advances in hardware technology for data collection, and advances in software technology (databases) for data organization, computer scientists have increasingly participated in the latest advancements of the outlier analysis field. Computer scientists, specifically, approach this field based on their practical experiences in managing large amounts of data, and with far fewer assumptions- the data can be of any type, structured or unstructured, and may be extremely large.Outlier Analysis is a comprehensive exposition, as understood by data mining experts, statisticians and

  5. Field analysis

    Directory of Open Access Journals (Sweden)

    Waindok Andrzej

    2017-12-01

    Full Text Available Field analysis including eddy currents in the magnetic core of five-phase permanent magnet tubular linear actuator (TLA has been carried out. The eddy currents induced in the magnetic core cause the losses which have been calculated. The results from 2D finite element (FE analysis have been compared with those from 3D calculations. The losses in the mover of the five-phase actuator are much lower than the losses in its stator. That is why the former ones can be neglected in the computer aided designing. The calculation results have been verified experimentally

  6. Numerical analysis

    CERN Document Server

    Brezinski, C

    2012-01-01

    Numerical analysis has witnessed many significant developments in the 20th century. This book brings together 16 papers dealing with historical developments, survey papers and papers on recent trends in selected areas of numerical analysis, such as: approximation and interpolation, solution of linear systems and eigenvalue problems, iterative methods, quadrature rules, solution of ordinary-, partial- and integral equations. The papers are reprinted from the 7-volume project of the Journal of Computational and Applied Mathematics on '/homepage/sac/cam/na2000/index.html<

  7. Clustering analysis

    International Nuclear Information System (INIS)

    Romli

    1997-01-01

    Cluster analysis is the name of group of multivariate techniques whose principal purpose is to distinguish similar entities from the characteristics they process.To study this analysis, there are several algorithms that can be used. Therefore, this topic focuses to discuss the algorithms, such as, similarity measures, and hierarchical clustering which includes single linkage, complete linkage and average linkage method. also, non-hierarchical clustering method, which is popular name K -mean method ' will be discussed. Finally, this paper will be described the advantages and disadvantages of every methods

  8. Image Analysis

    DEFF Research Database (Denmark)

    . The topics of the accepted papers range from novel applications of vision systems, pattern recognition, machine learning, feature extraction, segmentation, 3D vision, to medical and biomedical image analysis. The papers originate from all the Scandinavian countries and several other European countries......The 19th Scandinavian Conference on Image Analysis was held at the IT University of Copenhagen in Denmark during June 15-17, 2015. The SCIA conference series has been an ongoing biannual event for more than 30 years and over the years it has nurtured a world-class regional research and development...

  9. Risk analysis

    International Nuclear Information System (INIS)

    Baron, J.H.; Nunez McLeod, J.; Rivera, S.S.

    1997-01-01

    This book contains a selection of research works performed in the CEDIAC Institute (Cuyo National University) in the area of Risk Analysis, with specific orientations to the subjects of uncertainty and sensitivity studies, software reliability, severe accident modeling, etc. This volume presents important material for all those researches who want to have an insight in the risk analysis field, as a tool to solution several problems frequently found in the engineering and applied sciences field, as well as for the academic teachers who want to keep up to date, including the new developments and improvements continuously arising in this field [es

  10. Convex analysis

    CERN Document Server

    Rockafellar, Ralph Tyrell

    2015-01-01

    Available for the first time in paperback, R. Tyrrell Rockafellar's classic study presents readers with a coherent branch of nonlinear mathematical analysis that is especially suited to the study of optimization problems. Rockafellar's theory differs from classical analysis in that differentiability assumptions are replaced by convexity assumptions. The topics treated in this volume include: systems of inequalities, the minimum or maximum of a convex function over a convex set, Lagrange multipliers, minimax theorems and duality, as well as basic results about the structure of convex sets and

  11. Elementary analysis

    CERN Document Server

    Snell, K S; Langford, W J; Maxwell, E A

    1966-01-01

    Elementary Analysis, Volume 2 introduces several of the ideas of modern mathematics in a casual manner and provides the practical experience in algebraic and analytic operations that lays a sound foundation of basic skills. This book focuses on the nature of number, algebraic and logical structure, groups, rings, fields, vector spaces, matrices, sequences, limits, functions and inverse functions, complex numbers, and probability. The logical structure of analysis given through the treatment of differentiation and integration, with applications to the trigonometric and logarithmic functions, is

  12. Cluster analysis

    CERN Document Server

    Everitt, Brian S; Leese, Morven; Stahl, Daniel

    2011-01-01

    Cluster analysis comprises a range of methods for classifying multivariate data into subgroups. By organizing multivariate data into such subgroups, clustering can help reveal the characteristics of any structure or patterns present. These techniques have proven useful in a wide range of areas such as medicine, psychology, market research and bioinformatics.This fifth edition of the highly successful Cluster Analysis includes coverage of the latest developments in the field and a new chapter dealing with finite mixture models for structured data.Real life examples are used throughout to demons

  13. Relativistic analysis

    International Nuclear Information System (INIS)

    Unterberger, A.

    1987-01-01

    We study the Klein-Gordon symbolic calculus of operators acting on solutions of the free Klein-Gordon equation. It contracts to the Weyl calculus as c→∞. Mathematically, it may also be considered as a pseudodifferential analysis on the unit ball of R n [fr

  14. Analysis paralysis

    Science.gov (United States)

    Bill Block

    2012-01-01

    I have been Editor-in-Chief for about 10 months now. Over that period of time, I have processed hundreds of manuscripts and considered hundreds of reviews. In doing so, I have noticed an emphasis on analysis at the expense of a better understanding of the ecological system under study. I mention this not to belittle statistical advances made within various disciplines...

  15. IWS analysis

    International Nuclear Information System (INIS)

    Rhoades, W.A.; Dray, B.J.

    1970-01-01

    The effect of Gadolinium-155 on the prompt kinetic behavior of a zirconium hydride reactor has been deduced, using experimental data from the SNAPTRAN machine. The poison material makes the temperature coefficient more positive, and the Type IV sleeves were deduced to give a positive coefficient above 1100 0 F. A thorough discussion of the data and analysis is included. (U.S.)

  16. Analysis report

    International Nuclear Information System (INIS)

    Saadi, Radouan; Marah, Hamid

    2014-01-01

    This report presents results related to Tritium analysis carried out at the CNESTEN DASTE in Rabat (Morocco), on behalf of Senegal, within the framework of the RAF7011 project. It describes analytical method and instrumentation including general uncertainty estimation: Electrolytic enrichment and liquid scintillation counting; The results are expressed in Tritium Unit (TU); Low Limit Detection: 0.02 TU

  17. Dimensional Analysis

    Indian Academy of Sciences (India)

    to understand and quite straightforward to use. Dimensional analysis is a topic which every student of 'science encounters in elementary physics courses. The basics of this topic are taught and learnt quite hurriedly (and forgotten fairly quickly thereafter!) It does not generally receive the attention and the respect it deserves ...

  18. Survival Analysis

    CERN Document Server

    Miller, Rupert G

    2011-01-01

    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  19. Poetic Analysis

    DEFF Research Database (Denmark)

    Nielsen, Kirsten

    2010-01-01

    The first part of this article presents the characteristics of Hebrew poetry: features associated with rhythm and phonology, grammatical features, structural elements like parallelism, and imagery and intertextuality. The second part consists of an analysis of Psalm 121. It is argued that assonance...

  20. Architecture Analysis

    NARCIS (Netherlands)

    Iacob, Maria-Eugenia; Jonkers, Henk; van der Torre, Leon; de Boer, Frank S.; Bonsangue, Marcello; Stam, Andries W.; Lankhorst, Marc M.; Quartel, Dick A.C.; Aldea, Adina; Lankhorst, Marc

    2017-01-01

    This chapter also explains what the added value of enterprise architecture analysis techniques is in addition to existing, more detailed, and domain-specific ones for business processes or software, for example. Analogous to the idea of using the ArchiMate enterprise modelling language to integrate

  1. Trend analysis

    International Nuclear Information System (INIS)

    Smith, M.; Jones, D.R.

    1991-01-01

    The goal of exploration is to find reserves that will earn an adequate rate of return on the capital invested. Neither exploration nor economics is an exact science. The authors must therefore explore in those trends (plays) that have the highest probability of achieving this goal. Trend analysis is a technique for organizing the available data to make these strategic exploration decisions objectively and is in conformance with their goals and risk attitudes. Trend analysis differs from resource estimation in its purpose. It seeks to determine the probability of economic success for an exploration program, not the ultimate results of the total industry effort. Thus the recent past is assumed to be the best estimate of the exploration probabilities for the near future. This information is combined with economic forecasts. The computer software tools necessary for trend analysis are (1) Information data base - requirements and sources. (2) Data conditioning program - assignment to trends, correction of errors, and conversion into usable form. (3) Statistical processing program - calculation of probability of success and discovery size probability distribution. (4) Analytical processing - Monte Carlo simulation to develop the probability distribution of the economic return/investment ratio for a trend. Limited capital (short-run) effects are analyzed using the Gambler's Ruin concept in the Monte Carlo simulation and by a short-cut method. Multiple trend analysis is concerned with comparing and ranking trends, allocating funds among acceptable trends, and characterizing program risk by using risk profiles. In summary, trend analysis is a reality check for long-range exploration planning

  2. Complex analysis

    CERN Document Server

    Freitag, Eberhard

    2005-01-01

    The guiding principle of this presentation of ``Classical Complex Analysis'' is to proceed as quickly as possible to the central results while using a small number of notions and concepts from other fields. Thus the prerequisites for understanding this book are minimal; only elementary facts of calculus and algebra are required. The first four chapters cover the essential core of complex analysis: - differentiation in C (including elementary facts about conformal mappings) - integration in C (including complex line integrals, Cauchy's Integral Theorem, and the Integral Formulas) - sequences and series of analytic functions, (isolated) singularities, Laurent series, calculus of residues - construction of analytic functions: the gamma function, Weierstrass' Factorization Theorem, Mittag-Leffler Partial Fraction Decomposition, and -as a particular highlight- the Riemann Mapping Theorem, which characterizes the simply connected domains in C. Further topics included are: - the theory of elliptic functions based on...

  3. Wavelet analysis

    CERN Document Server

    Cheng, Lizhi; Luo, Yong; Chen, Bo

    2014-01-01

    This book could be divided into two parts i.e. fundamental wavelet transform theory and method and some important applications of wavelet transform. In the first part, as preliminary knowledge, the Fourier analysis, inner product space, the characteristics of Haar functions, and concepts of multi-resolution analysis, are introduced followed by a description on how to construct wavelet functions both multi-band and multi wavelets, and finally introduces the design of integer wavelets via lifting schemes and its application to integer transform algorithm. In the second part, many applications are discussed in the field of image and signal processing by introducing other wavelet variants such as complex wavelets, ridgelets, and curvelets. Important application examples include image compression, image denoising/restoration, image enhancement, digital watermarking, numerical solution of partial differential equations, and solving ill-conditioned Toeplitz system. The book is intended for senior undergraduate stude...

  4. Harmonic analysis

    CERN Document Server

    Helson, Henry

    2010-01-01

    This second edition has been enlarged and considerably rewritten. Among the new topics are infinite product spaces with applications to probability, disintegration of measures on product spaces, positive definite functions on the line, and additional information about Weyl's theorems on equidistribution. Topics that have continued from the first edition include Minkowski's theorem, measures with bounded powers, idempotent measures, spectral sets of bounded functions and a theorem of Szego, and the Wiener Tauberian theorem. Readers of the book should have studied the Lebesgue integral, the elementary theory of analytic and harmonic functions, and the basic theory of Banach spaces. The treatment is classical and as simple as possible. This is an instructional book, not a treatise. Mathematics students interested in analysis will find here what they need to know about Fourier analysis. Physicists and others can use the book as a reference for more advanced topics.

  5. Geometric analysis

    CERN Document Server

    Bray, Hubert L; Mazzeo, Rafe; Sesum, Natasa

    2015-01-01

    This volume includes expanded versions of the lectures delivered in the Graduate Minicourse portion of the 2013 Park City Mathematics Institute session on Geometric Analysis. The papers give excellent high-level introductions, suitable for graduate students wishing to enter the field and experienced researchers alike, to a range of the most important areas of geometric analysis. These include: the general issue of geometric evolution, with more detailed lectures on Ricci flow and Kähler-Ricci flow, new progress on the analytic aspects of the Willmore equation as well as an introduction to the recent proof of the Willmore conjecture and new directions in min-max theory for geometric variational problems, the current state of the art regarding minimal surfaces in R^3, the role of critical metrics in Riemannian geometry, and the modern perspective on the study of eigenfunctions and eigenvalues for Laplace-Beltrami operators.

  6. [OSTEOMETRIC ANALYSIS].

    Science.gov (United States)

    Tartaglia, Gianna; Nava, Alessia

    2015-01-01

    In the paleobiological studies, the osteometry is a method for gaining insight into human populations of the past. The analysis of the data obtained from measurements of the skeleton can be applied in the determination of sex and degree of sexual dimorphism intra and interpopulation. The results obtained from osteometrical data of postcranial allow us to formulate hypotheses on certain aspects related to the living conditions of the people who lived in the urban and suburban area of ancient Rome.

  7. Survival analysis

    International Nuclear Information System (INIS)

    Badwe, R.A.

    1999-01-01

    The primary endpoint in the majority of the studies has been either disease recurrence or death. This kind of analysis requires a special method since all patients in the study experience the endpoint. The standard method for estimating such survival distribution is Kaplan Meier method. The survival function is defined as the proportion of individuals who survive beyond certain time. Multi-variate comparison for survival has been carried out with Cox's proportional hazard model

  8. Water analysis

    International Nuclear Information System (INIS)

    Garbarino, J.R.; Steinheimer, T.R.; Taylor, H.E.

    1985-01-01

    This is the twenty-first biennial review of the inorganic and organic analytical chemistry of water. The format of this review differs somewhat from previous reviews in this series - the most recent of which appeared in Analytical Chemistry in April 1983. Changes in format have occurred in the presentation of material concerning review articles and the inorganic analysis of water sections. Organic analysis of water sections are organized as in previous reviews. Review articles have been compiled and tabulated in an Appendix with respect to subject, title, author(s), citation, and number of references cited. The inorganic water analysis sections are now grouped by constituent using the periodic chart; for example, alkali, alkaline earth, 1st series transition metals, etc. Within these groupings the references are roughly grouped by instrumental technique; for example, spectrophotometry, atomic absorption spectrometry, etc. Multiconstituent methods for determining analytes that cannot be grouped in this manner are compiled into a separate section sorted by instrumental technique. References used in preparing this review were compiled from nearly 60 major journals published during the period from October 1982 through September 1984. Conference proceedings, most foreign journals, most trade journals, and most government publications are excluded. References cited were obtained using the American Chemical Society's Chemical Abstracts for sections on inorganic analytical chemistry, organic analytical chemistry, water, and sewage waste. Cross-references of these sections were also included. 860 references

  9. Economic analysis

    Energy Technology Data Exchange (ETDEWEB)

    None

    1980-06-01

    The Energy Policy and Conservation Act (EPCA) mandated that minimum energy efficiency standards be established for classes of refrigerators and refrigerator-freezers, freezers, clothes dryers, water heaters, room air conditioners, home heating equipment, kitchen ranges and ovens, central air conditioners, and furnaces. EPCA requires that standards be designed to achieve the maximum improvement in energy efficiency that is technologically feasible and economically justified. Following the introductory chapter, Chapter Two describes the methodology used in the economic analysis and its relationship to legislative criteria for consumer product efficiency assessment; details how the CPES Value Model systematically compared and evaluated the economic impacts of regulation on the consumer, manufacturer and Nation. Chapter Three briefly displays the results of the analysis and lists the proposed performance standards by product class. Chapter Four describes the reasons for developing a baseline forecast, characterizes the baseline scenario from which regulatory impacts were calculated and summarizes the primary models, data sources and assumptions used in the baseline formulations. Chapter Five summarizes the methodology used to calculate regulatory impacts; describes the impacts of energy performance standards relative to the baseline discussed in Chapter Four. Also discussed are regional standards and other program alternatives to performance standards. Chapter Six describes the procedure for balancing consumer, manufacturer, and national impacts to select standard levels. Details of models and data bases used in the analysis are included in Appendices A through K.

  10. Integrating transcriptomics and metabonomics to unravel modes-of-action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in HepG2 cells

    NARCIS (Netherlands)

    Jennen, D.G.J.; Ruiz-Aracama, A.; Magkoufopoulou, C.; Peijnenburg, A.A.C.M.; Lommen, A.; Delft, van J.; Kleinjans, J.C.S.

    2011-01-01

    Background The integration of different 'omics' technologies has already been shown in several in vivo studies to offer a complementary insight into cellular responses to toxic challenges. Being interested in developing in vitro cellular models as alternative to animal-based toxicity assays, we

  11. Activation analysis

    International Nuclear Information System (INIS)

    Beeck, J. OP de

    1977-01-01

    It is shown that activation analysis is especially suited to serve as a basis for determining the chemical similarity between samples defined by their trace-element concentration patterns. The general problem of classification and identification is discussed. The nature of possible classification structures and their appropriate clustering strategies is considered. A practical computer method is suggested and its application as well as the graphical representation of classification results are given. The possibility for classification using information theory is mentioned. Classification of chemical elements is discussed and practically realized after Hadamard transformation of the concentration variation patterns in a series of samples. (Sz.N.Z.)

  12. Exergy analysis

    DEFF Research Database (Denmark)

    Dovjak, M.; Simone, Angela; Kolarik, Jakub

    2011-01-01

    Exergy analysis enables us to make connections among processes inside the human body and processes in a building. So far, only the effect of different combinations of air temperatures and mean radiant temperatures have been studied, with constant relative humidity in experimental conditions...... al. (1998). The effect of different levels of RH, Ta and effective clothing insulation on human body exergy balance chain, changes in human body exergy consumption rate (hbExCr) and predicted mean vote (PMV) index were analyzed. The results show that thermal comfort conditions do not always results...

  13. Complex Analysis

    CERN Document Server

    Stein, Elias M

    2009-01-01

    With this second volume, we enter the intriguing world of complex analysis. From the first theorems on, the elegance and sweep of the results is evident. The starting point is the simple idea of extending a function initially given for real values of the argument to one that is defined when the argument is complex. From there, one proceeds to the main properties of holomorphic functions, whose proofs are generally short and quite illuminating: the Cauchy theorems, residues, analytic continuation, the argument principle.With this background, the reader is ready to learn a wealth of additional m

  14. Vector analysis

    CERN Document Server

    Newell, Homer E

    2006-01-01

    When employed with skill and understanding, vector analysis can be a practical and powerful tool. This text develops the algebra and calculus of vectors in a manner useful to physicists and engineers. Numerous exercises (with answers) not only provide practice in manipulation but also help establish students' physical and geometric intuition in regard to vectors and vector concepts.Part I, the basic portion of the text, consists of a thorough treatment of vector algebra and the vector calculus. Part II presents the illustrative matter, demonstrating applications to kinematics, mechanics, and e

  15. Sequential analysis

    CERN Document Server

    Wald, Abraham

    2013-01-01

    In 1943, while in charge of Columbia University's Statistical Research Group, Abraham Wald devised Sequential Design, an innovative statistical inference system. Because the decision to terminate an experiment is not predetermined, sequential analysis can arrive at a decision much sooner and with substantially fewer observations than equally reliable test procedures based on a predetermined number of observations. The system's immense value was immediately recognized, and its use was restricted to wartime research and procedures. In 1945, it was released to the public and has since revolutio

  16. Vector analysis

    CERN Document Server

    Brand, Louis

    2006-01-01

    The use of vectors not only simplifies treatments of differential geometry, mechanics, hydrodynamics, and electrodynamics, but also makes mathematical and physical concepts more tangible and easy to grasp. This text for undergraduates was designed as a short introductory course to give students the tools of vector algebra and calculus, as well as a brief glimpse into these subjects' manifold applications. The applications are developed to the extent that the uses of the potential function, both scalar and vector, are fully illustrated. Moreover, the basic postulates of vector analysis are brou

  17. Understanding analysis

    CERN Document Server

    Abbott, Stephen

    2015-01-01

    This lively introductory text exposes the student to the rewards of a rigorous study of functions of a real variable. In each chapter, informal discussions of questions that give analysis its inherent fascination are followed by precise, but not overly formal, developments of the techniques needed to make sense of them. By focusing on the unifying themes of approximation and the resolution of paradoxes that arise in the transition from the finite to the infinite, the text turns what could be a daunting cascade of definitions and theorems into a coherent and engaging progression of ideas. Acutely aware of the need for rigor, the student is much better prepared to understand what constitutes a proper mathematical proof and how to write one. Fifteen years of classroom experience with the first edition of Understanding Analysis have solidified and refined the central narrative of the second edition. Roughly 150 new exercises join a selection of the best exercises from the first edition, and three more project-sty...

  18. Failure Analysis

    International Nuclear Information System (INIS)

    Iorio, A.F.; Crespi, J.C.

    1987-01-01

    After ten years of operation at the Atucha I Nuclear Power Station a gear belonging to a pressurized heavy water reactor refuelling machine, failed. The gear box was used to operate the inlet-outlet heavy-water valve of the machine. Visual examination of the gear device showed an absence of lubricant and that several gear teeth were broken at the root. Motion was transmitted with a speed-reducing device with controlled adjustable times in order to produce a proper fitness of the valve closure. The aim of this paper is to discuss the results of the gear failure analysis in order to recommend the proper solution to prevent further failures. (Author)

  19. Matrix analysis

    CERN Document Server

    Bhatia, Rajendra

    1997-01-01

    A good part of matrix theory is functional analytic in spirit. This statement can be turned around. There are many problems in operator theory, where most of the complexities and subtleties are present in the finite-dimensional case. My purpose in writing this book is to present a systematic treatment of methods that are useful in the study of such problems. This book is intended for use as a text for upper division and gradu­ ate courses. Courses based on parts of the material have been given by me at the Indian Statistical Institute and at the University of Toronto (in collaboration with Chandler Davis). The book should also be useful as a reference for research workers in linear algebra, operator theory, mathe­ matical physics and numerical analysis. A possible subtitle of this book could be Matrix Inequalities. A reader who works through the book should expect to become proficient in the art of deriving such inequalities. Other authors have compared this art to that of cutting diamonds. One first has to...

  20. Functional analysis

    CERN Document Server

    Kesavan, S

    2009-01-01

    The material presented in this book is suited for a first course in Functional Analysis which can be followed by Masters students. While covering all the standard material expected of such a course, efforts have been made to illustrate the use of various theorems via examples taken from differential equations and the calculus of variations, either through brief sections or through exercises. In fact, this book will be particularly useful for students who would like to pursue a research career in the applications of mathematics. The book includes a chapter on weak and weak topologies and their applications to the notions of reflexivity, separability and uniform convexity. The chapter on the Lebesgue spaces also presents the theory of one of the simplest classes of Sobolev spaces. The book includes a chapter on compact operators and the spectral theory for compact self-adjoint operators on a Hilbert space. Each chapter has large collection of exercises at the end. These illustrate the results of the text, show ...

  1. Uncertainty analysis

    International Nuclear Information System (INIS)

    Thomas, R.E.

    1982-03-01

    An evaluation is made of the suitability of analytical and statistical sampling methods for making uncertainty analyses. The adjoint method is found to be well-suited for obtaining sensitivity coefficients for computer programs involving large numbers of equations and input parameters. For this purpose the Latin Hypercube Sampling method is found to be inferior to conventional experimental designs. The Latin hypercube method can be used to estimate output probability density functions, but requires supplementary rank transformations followed by stepwise regression to obtain uncertainty information on individual input parameters. A simple Cork and Bottle problem is used to illustrate the efficiency of the adjoint method relative to certain statistical sampling methods. For linear models of the form Ax=b it is shown that a complete adjoint sensitivity analysis can be made without formulating and solving the adjoint problem. This can be done either by using a special type of statistical sampling or by reformulating the primal problem and using suitable linear programming software

  2. Uncertainty analysis

    Energy Technology Data Exchange (ETDEWEB)

    Thomas, R.E.

    1982-03-01

    An evaluation is made of the suitability of analytical and statistical sampling methods for making uncertainty analyses. The adjoint method is found to be well-suited for obtaining sensitivity coefficients for computer programs involving large numbers of equations and input parameters. For this purpose the Latin Hypercube Sampling method is found to be inferior to conventional experimental designs. The Latin hypercube method can be used to estimate output probability density functions, but requires supplementary rank transformations followed by stepwise regression to obtain uncertainty information on individual input parameters. A simple Cork and Bottle problem is used to illustrate the efficiency of the adjoint method relative to certain statistical sampling methods. For linear models of the form Ax=b it is shown that a complete adjoint sensitivity analysis can be made without formulating and solving the adjoint problem. This can be done either by using a special type of statistical sampling or by reformulating the primal problem and using suitable linear programming software.

  3. Information security risk analysis

    CERN Document Server

    Peltier, Thomas R

    2001-01-01

    Effective Risk AnalysisQualitative Risk AnalysisValue AnalysisOther Qualitative MethodsFacilitated Risk Analysis Process (FRAP)Other Uses of Qualitative Risk AnalysisCase StudyAppendix A: QuestionnaireAppendix B: Facilitated Risk Analysis Process FormsAppendix C: Business Impact Analysis FormsAppendix D: Sample of ReportAppendix E: Threat DefinitionsAppendix F: Other Risk Analysis OpinionsIndex

  4. NMR-based metabolomics reveals that conjugated double bond content and lipid storage efficiency in HepG2 cells are affected by fatty acid cis/trans configuration and chain length

    DEFF Research Database (Denmark)

    Najbjerg, Heidi; Young, Jette F; Bertram, Hanne Christine S.

    2011-01-01

    In the present study the metabolic response to various fatty acids was investigated in HepG2 cells by using a 1HNMRbased approach. To elucidate the effect of cis/trans configuration, the cells were exposed to either oleic acid (C18:1 cis-9), elaidic acid (C18:1 trans-9), vaccenic acid (C18:1 tran...

  5. Glucosinolate diversity within a phylogenetic framework of the tribe Cardamineae (Brassicaceae) unraveled with HPLC-MS/MS and NMR-based analytical distinction of 70 desulfoglucosinolates

    DEFF Research Database (Denmark)

    Olsen, Carl Erik; Huang, Xiao-Chen; Hansen, Cecilie Ida Cetti

    2016-01-01

    As a basis for future investigations of evolutionary trajectories and biosynthetic mechanisms underlying variations in glucosinolate structures, we screened members of the crucifer tribe Cardamineae by HPLC-MS/MS, isolated and identified glucosinolates by NMR, searched the literature for previous...

  6. Pyrotechnic Shock Analysis Using Statistical Energy Analysis

    Science.gov (United States)

    2015-10-23

    2013. 3. Lyon, Richard H., and DeJong, Richard G., “ Theory and Application of Statistical Energy Analysis, 2nd Edition,” Butterworth-Heinemann, 1995... Dalton , Eric C., “Ballistic Shock Response Prediction through the Synergistic Use of Statistical Energy Analysis, Finite Element Analysis, and

  7. Safety analysis fundamentals

    International Nuclear Information System (INIS)

    Wright, A.C.D.

    2002-01-01

    This paper discusses the safety analysis fundamentals in reactor design. This study includes safety analysis done to show consequences of postulated accidents are acceptable. Safety analysis is also used to set design of special safety systems and includes design assist analysis to support conceptual design. safety analysis is necessary for licensing a reactor, to maintain an operating license, support changes in plant operations

  8. Urine metabolomics in rats after administration of ketamine

    Directory of Open Access Journals (Sweden)

    Wen C

    2015-02-01

    Full Text Available Congcong Wen,1 Meiling Zhang,2 Jianshe Ma,2 Lufeng Hu,3 Xianqin Wang,2 Guanyang Lin31Laboratory Animal Centre, 2Analytical and Testing Center, 3First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of ChinaAbstract: In this study, we developed a urine metabonomic method, based on gas chromatography–mass spectrometry (GC-MS, to evaluate the effect of ketamine on rats. Pattern recognition analysis, including both principal component analysis and partial least squares discriminate analysis revealed that ketamine (50 mg/kg induced metabolic perturbations. Compared with the control group, at day 7, the level of alanine, butanoic acid, glutamine, butanedioic, trimethylsiloxy, L-aspartic acid, D-glucose, cholesterol, acetamide, and oleic acid of the ketamine group was increased, while the level of 2,3,4-trihydroxybutyric acid, benzene­acetic acid, threitol, ribitol, xylitol, and glycine decreased. At day 14, the level of alanine, ethanedioic acid, L-proline, glycerol, tetradecanoic acid, l-serine, l-phenylalanine, L-aspartic acid, d-glucose, cholesterol, heptadecanoic acid, and acetamide in rat urine of the ketamine group was increased, while the 2,3,4-trihydroxybutyric acid, benzeneacetic acid, d-ribose, threitol, ribitol, glycine, pyrazine, and oleic acid levels decreased. Our results indicate that metabonomic methods based on GC-MS may be useful to elucidate ketamine abuse, through the exploration of biomarkers.Keywords: GC-MS, abuse, biomarker, metabolite

  9. Metabolic characterization of the early stage of hepatic fibrosis in rat using GC-TOF/MS and multivariate data analyses.

    Science.gov (United States)

    Jiang, Hui; Song, Jun-Mei; Gao, Peng-Fei; Qin, Xiu-Juan; Xu, Shuang-Zhi; Zhang, Jia-Fu

    2017-06-01

    The aim of this study was to explore the changes in the urine metabolic spectrum in rats with the early stage of liver fibrosis using gas chromatography-time of flight/mass spectrometry (GC-TOF/MS), try to search for potential biomarkers and elucidate the probably metabonomic pathogenesis. The early stage of liver fibrosis was established with a single subcutaneous injection of carbon tetrachloride twice each week for 4 weeks continuously. At the end of the experiment, GC-TOF/MS technology with multivariate statistical approaches such as principal component analysis, partial least squares-discriminant analysis and orthogonal partial least squares-discriminant analysis was used to analyze the changes in the metabolic spectrum trajectory and identify potential biomarkers. Twelve potential biomarkers in the model group, such as succinic acid, threonine and lactose, were selected, which indicate that the metabonomic pathogenesis of the early stage of liver fibrosis may be related to disorders of energy metabolism, amino acid metabolism and fatty acid metabolism. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Metabolic changes in rat urine after acute paraquat poisoning and discriminated by support vector machine.

    Science.gov (United States)

    Wen, Congcong; Wang, Zhiyi; Zhang, Meiling; Wang, Shuanghu; Geng, Peiwu; Sun, Fa; Chen, Mengchun; Lin, Guanyang; Hu, Lufeng; Ma, Jianshe; Wang, Xianqin

    2016-01-01

    Paraquat is quick-acting and non-selective, killing green plant tissue on contact; it is also toxic to human beings and animals. In this study, we developed a urine metabonomic method by gas chromatography-mass spectrometry to evaluate the effect of acute paraquat poisoning on rats. Pattern recognition analysis, including both partial least squares discriminate analysis and principal component analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared with the control group, the levels of benzeneacetic acid and hexadecanoic acid of the acute paraquat poisoning group (intragastric administration 36 mg/kg) increased, while the levels of butanedioic acid, pentanedioic acid, altronic acid decreased. Based on these urinary metabolomics data, support vector machine was applied to discriminate the metabolomic change of paraquat groups from the control group, which achieved 100% classification accuracy. In conclusion, metabonomic method combined with support vector machine can be used as a useful diagnostic tool in paraquat-poisoned rats. Copyright © 2015 John Wiley & Sons, Ltd.

  11. Shape analysis in medical image analysis

    CERN Document Server

    Tavares, João

    2014-01-01

    This book contains thirteen contributions from invited experts of international recognition addressing important issues in shape analysis in medical image analysis, including techniques for image segmentation, registration, modelling and classification, and applications in biology, as well as in cardiac, brain, spine, chest, lung and clinical practice. This volume treats topics such as, anatomic and functional shape representation and matching; shape-based medical image segmentation; shape registration; statistical shape analysis; shape deformation; shape-based abnormity detection; shape tracking and longitudinal shape analysis; machine learning for shape modeling and analysis; shape-based computer-aided-diagnosis; shape-based medical navigation; benchmark and validation of shape representation, analysis and modeling algorithms. This work will be of interest to researchers, students, and manufacturers in the fields of artificial intelligence, bioengineering, biomechanics, computational mechanics, computationa...

  12. Integrated Sensitivity Analysis Workflow

    Energy Technology Data Exchange (ETDEWEB)

    Friedman-Hill, Ernest J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Hoffman, Edward L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Gibson, Marcus J. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Clay, Robert L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-08-01

    Sensitivity analysis is a crucial element of rigorous engineering analysis, but performing such an analysis on a complex model is difficult and time consuming. The mission of the DART Workbench team at Sandia National Laboratories is to lower the barriers to adoption of advanced analysis tools through software integration. The integrated environment guides the engineer in the use of these integrated tools and greatly reduces the cycle time for engineering analysis.

  13. K Basin Hazard Analysis

    International Nuclear Information System (INIS)

    PECH, S.H.

    2000-01-01

    This report describes the methodology used in conducting the K Basins Hazard Analysis, which provides the foundation for the K Basins Final Safety Analysis Report. This hazard analysis was performed in accordance with guidance provided by DOE-STD-3009-94, Preparation Guide for U. S. Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports and implements the requirements of DOE Order 5480.23, Nuclear Safety Analysis Report

  14. K Basin Hazard Analysis

    Energy Technology Data Exchange (ETDEWEB)

    PECH, S.H.

    2000-08-23

    This report describes the methodology used in conducting the K Basins Hazard Analysis, which provides the foundation for the K Basins Final Safety Analysis Report. This hazard analysis was performed in accordance with guidance provided by DOE-STD-3009-94, Preparation Guide for U. S. Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports and implements the requirements of DOE Order 5480.23, Nuclear Safety Analysis Report.

  15. K Basins Hazard Analysis

    International Nuclear Information System (INIS)

    WEBB, R.H.

    1999-01-01

    This report describes the methodology used in conducting the K Basins Hazard Analysis, which provides the foundation for the K Basins Safety Analysis Report (HNF-SD-WM-SAR-062/Rev.4). This hazard analysis was performed in accordance with guidance provided by DOE-STD-3009-94, Preparation Guide for U. S. Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports and implements the requirements of DOE Order 5480.23, Nuclear Safety Analysis Report

  16. Qualitative Content Analysis

    OpenAIRE

    Philipp Mayring

    2000-01-01

    The article describes an approach of systematic, rule guided qualitative text analysis, which tries to preserve some methodological strengths of quantitative content analysis and widen them to a concept of qualitative procedure. First the development of content analysis is delineated and the basic principles are explained (units of analysis, step models, working with categories, validity and reliability). Then the central procedures of qualitative content analysis, inductive development of ca...

  17. Quantitative analysis chemistry

    International Nuclear Information System (INIS)

    Ko, Wansuk; Lee, Choongyoung; Jun, Kwangsik; Hwang, Taeksung

    1995-02-01

    This book is about quantitative analysis chemistry. It is divided into ten chapters, which deal with the basic conception of material with the meaning of analysis chemistry and SI units, chemical equilibrium, basic preparation for quantitative analysis, introduction of volumetric analysis, acid-base titration of outline and experiment examples, chelate titration, oxidation-reduction titration with introduction, titration curve, and diazotization titration, precipitation titration, electrometric titration and quantitative analysis.

  18. Analysis of Precision of Activation Analysis Method

    DEFF Research Database (Denmark)

    Heydorn, Kaj; Nørgaard, K.

    1973-01-01

    The precision of an activation-analysis method prescribes the estimation of the precision of a single analytical result. The adequacy of these estimates to account for the observed variation between duplicate results from the analysis of different samples and materials, is tested by the statistic T...

  19. Sentiment Analysis for Exploratory Data Analysis

    Directory of Open Access Journals (Sweden)

    Zoë Wilkinson Saldaña

    2018-01-01

    Full Text Available In this lesson you will learn to conduct 'sentiment analysis' on texts and to interpret the results. This is a form of exploratory data analysis based on natural language processing. You will learn to install all appropriate software and to build a reusable program that can be applied to your own texts.

  20. Metabolic responses of Eisenia fetida after sub-lethal exposure to organic contaminants with different toxic modes of action

    Energy Technology Data Exchange (ETDEWEB)

    McKelvie, Jennifer R.; Wolfe, David M.; Celejewski, Magda A. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Alaee, Mehran [Environment Canada, 867 Lakeshore Rd., P.O. Box 5050, Burlington, ON L7R 4A6 (Canada); Simpson, Andre J. [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada); Simpson, Myrna J., E-mail: myrna.simpson@utoronto.ca [Department of Physical and Environmental Sciences, University of Toronto, 1265 Military Trail Toronto, ON M1C 1A4 (Canada)

    2011-12-15

    Nuclear magnetic resonance (NMR) - based metabolomics has the potential to identify toxic responses of contaminants within a mixture in contaminated soil. This study evaluated the metabolic response of Eisenia fetida after exposure to an array of organic compounds to determine whether contaminant-specific responses could be identified. The compounds investigated in contact tests included: two pesticides (carbaryl and chlorpyrifos), three pharmaceuticals (carbamazephine, estrone and caffeine), two persistent organohalogens (Aroclor 1254 and PBDE 209) and two industrial compounds (nonylphenol and dimethyl phthalate). Control and contaminant-exposed metabolic profiles were distinguished using principal component analysis and potential contaminant-specific biomarkers of exposure were found for several contaminants. These results suggest that NMR-based metabolomics offers considerable promise for differentiating between the different toxic modes of action (MOA) associated with sub-lethal toxicity to earthworms. - Highlights: > NMR-based earthworm metabolomic analysis of the toxic mode of action of various environmental contaminants. > Organic chemicals with different toxic modes of action resulted in varied metabolomic responses for E. fetida. > NMR-based metabolomics differentiates between the different modes of action associated with sub-lethal toxicity. - {sup 1}H NMR metabolomics was used to identify potential biomarkers of organic contaminant exposure in Eisenia fetida earthworms.

  1. Hazard Analysis Database Report

    CERN Document Server

    Grams, W H

    2000-01-01

    The Hazard Analysis Database was developed in conjunction with the hazard analysis activities conducted in accordance with DOE-STD-3009-94, Preparation Guide for U S . Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports, for HNF-SD-WM-SAR-067, Tank Farms Final Safety Analysis Report (FSAR). The FSAR is part of the approved Authorization Basis (AB) for the River Protection Project (RPP). This document describes, identifies, and defines the contents and structure of the Tank Farms FSAR Hazard Analysis Database and documents the configuration control changes made to the database. The Hazard Analysis Database contains the collection of information generated during the initial hazard evaluations and the subsequent hazard and accident analysis activities. The Hazard Analysis Database supports the preparation of Chapters 3 ,4 , and 5 of the Tank Farms FSAR and the Unreviewed Safety Question (USQ) process and consists of two major, interrelated data sets: (1) Hazard Analysis Database: Data from t...

  2. Cluster analysis for applications

    CERN Document Server

    Anderberg, Michael R

    1973-01-01

    Cluster Analysis for Applications deals with methods and various applications of cluster analysis. Topics covered range from variables and scales to measures of association among variables and among data units. Conceptual problems in cluster analysis are discussed, along with hierarchical and non-hierarchical clustering methods. The necessary elements of data analysis, statistics, cluster analysis, and computer implementation are integrated vertically to cover the complete path from raw data to a finished analysis.Comprised of 10 chapters, this book begins with an introduction to the subject o

  3. Circuit analysis for dummies

    CERN Document Server

    Santiago, John

    2013-01-01

    Circuits overloaded from electric circuit analysis? Many universities require that students pursuing a degree in electrical or computer engineering take an Electric Circuit Analysis course to determine who will ""make the cut"" and continue in the degree program. Circuit Analysis For Dummies will help these students to better understand electric circuit analysis by presenting the information in an effective and straightforward manner. Circuit Analysis For Dummies gives you clear-cut information about the topics covered in an electric circuit analysis courses to help

  4. Canonical Information Analysis

    DEFF Research Database (Denmark)

    Vestergaard, Jacob Schack; Nielsen, Allan Aasbjerg

    2015-01-01

    Canonical correlation analysis is an established multivariate statistical method in which correlation between linear combinations of multivariate sets of variables is maximized. In canonical information analysis introduced here, linear correlation as a measure of association between variables is ...

  5. Introductory numerical analysis

    CERN Document Server

    Pettofrezzo, Anthony J

    2006-01-01

    Written for undergraduates who require a familiarity with the principles behind numerical analysis, this classical treatment encompasses finite differences, least squares theory, and harmonic analysis. Over 70 examples and 280 exercises. 1967 edition.

  6. Ecosystem Analysis Program

    International Nuclear Information System (INIS)

    Burgess, R.L.

    1978-01-01

    Progress is reported on the following research programs: analysis and modeling of ecosystems; EDFB/IBP data center; biome analysis studies; land/water interaction studies; and computer programs for development of models

  7. Importance-performance analysis based SWOT analysis

    OpenAIRE

    Phadermrod, Boonyarat; Crowder, Richard M.; Wills, Gary B.

    2016-01-01

    SWOT analysis, a commonly used tool for strategic planning, is traditionally a form of brainstorming. Hence, it has been criticised that it is likely to hold subjective views of the individuals who participate in a brainstorming session and that SWOT factors are not prioritized by their significance thus it may result in an improper strategic action. While most studies of SWOT analysis have only focused on solving these shortcomings separately, this study offers an approach to diminish both s...

  8. Computational movement analysis

    CERN Document Server

    Laube, Patrick

    2014-01-01

    This SpringerBrief discusses the characteristics of spatiotemporal movement data, including uncertainty and scale. It investigates three core aspects of Computational Movement Analysis: Conceptual modeling of movement and movement spaces, spatiotemporal analysis methods aiming at a better understanding of movement processes (with a focus on data mining for movement patterns), and using decentralized spatial computing methods in movement analysis. The author presents Computational Movement Analysis as an interdisciplinary umbrella for analyzing movement processes with methods from a range of fi

  9. Regression analysis by example

    CERN Document Server

    Chatterjee, Samprit

    2012-01-01

    Praise for the Fourth Edition: ""This book is . . . an excellent source of examples for regression analysis. It has been and still is readily readable and understandable."" -Journal of the American Statistical Association Regression analysis is a conceptually simple method for investigating relationships among variables. Carrying out a successful application of regression analysis, however, requires a balance of theoretical results, empirical rules, and subjective judgment. Regression Analysis by Example, Fifth Edition has been expanded

  10. Applied longitudinal analysis

    CERN Document Server

    Fitzmaurice, Garrett M; Ware, James H

    2012-01-01

    Praise for the First Edition "". . . [this book] should be on the shelf of everyone interested in . . . longitudinal data analysis.""-Journal of the American Statistical Association   Features newly developed topics and applications of the analysis of longitudinal data Applied Longitudinal Analysis, Second Edition presents modern methods for analyzing data from longitudinal studies and now features the latest state-of-the-art techniques. The book emphasizes practical, rather than theoretical, aspects of methods for the analysis of diverse types of lo

  11. Discourse analysis and Foucault's

    Directory of Open Access Journals (Sweden)

    Jansen I.

    2008-01-01

    Full Text Available Discourse analysis is a method with up to now was less recognized in nursing science, althoughmore recently nursing scientists are discovering it for their purposes. However, several authors have criticized thatdiscourse analysis is often misinterpreted because of a lack of understanding of its theoretical backgrounds. In thisarticle, I reconstruct Foucault’s writings in his “Archaeology of Knowledge” to provide a theoretical base for futurearchaeological discourse analysis, which can be categorized as a socio-linguistic discourse analysis.

  12. Nonstandard Analysis and Constructivism!

    OpenAIRE

    Sanders, Sam

    2017-01-01

    Almost two decades ago, Wattenberg published a paper with the title 'Nonstandard Analysis and Constructivism?' in which he speculates on a possible connection between Nonstandard Analysis and constructive mathematics. We study Wattenberg's work in light of recent research on the aforementioned connection. On one hand, with only slight modification, some of Wattenberg's theorems in Nonstandard Analysis are seen to yield effective and constructive theorems (not involving Nonstandard Analysis). ...

  13. Analysis of extreme events

    CSIR Research Space (South Africa)

    Khuluse, S

    2009-04-01

    Full Text Available the stability of the parameter estimates. 9 / 27 Background Overview of the Theory of Extremes Case Studies Concluding Remarks Analysis of Extreme Rainfall Events Analysis of Extreme Wave Heights Figure: Map of South Africa with the study areas... highlighted 10 / 27 Background Overview of the Theory of Extremes Case Studies Concluding Remarks Analysis of Extreme Rainfall Events Analysis of Extreme Wave Heights Western Cape Climatologically diverse: Influence of the varied topography and it’s...

  14. Biological sequence analysis

    DEFF Research Database (Denmark)

    Durbin, Richard; Eddy, Sean; Krogh, Anders Stærmose

    This book provides an up-to-date and tutorial-level overview of sequence analysis methods, with particular emphasis on probabilistic modelling. Discussed methods include pairwise alignment, hidden Markov models, multiple alignment, profile searches, RNA secondary structure analysis, and phylogene......This book provides an up-to-date and tutorial-level overview of sequence analysis methods, with particular emphasis on probabilistic modelling. Discussed methods include pairwise alignment, hidden Markov models, multiple alignment, profile searches, RNA secondary structure analysis...

  15. Principal component analysis

    NARCIS (Netherlands)

    Bro, R.; Smilde, A.K.

    2014-01-01

    Principal component analysis is one of the most important and powerful methods in chemometrics as well as in a wealth of other areas. This paper provides a description of how to understand, use, and interpret principal component analysis. The paper focuses on the use of principal component analysis

  16. Charged particle activation analysis

    International Nuclear Information System (INIS)

    Peisach, M.

    1977-01-01

    The techniques of prompt and delayed activation analysis are outlined. Methods using cyclotron beams are suitable for delayed A.A., but prompt methods with relatively low energy beams serve a useful purpose for analysis of thin layers and surfaces. Multi-element analyses with prompt X-rays, generally applicable analysis by backscattering and specific analyses by nuclaer reactions are described [af

  17. Critical Classroom Discourse Analysis.

    Science.gov (United States)

    Kumaravadivelu, B.

    1999-01-01

    Conceptualizes a framework for conducting critical classroom-discourse analysis. Critiques the scope and method of current models of classroom-interaction analysis and classroom-discourse analysis and advocates using poststructuralist and postcolonialist understandings of discourse to develop a critical framework for understanding what actually…

  18. Practical data analysis

    CERN Document Server

    Cuesta, Hector

    2013-01-01

    Each chapter of the book quickly introduces a key 'theme' of Data Analysis, before immersing you in the practical aspects of each theme. You'll learn quickly how to perform all aspects of Data Analysis.Practical Data Analysis is a book ideal for home and small business users who want to slice & dice the data they have on hand with minimum hassle.

  19. Data analysis for chemistry

    CERN Document Server

    Hibbert, DBrynn

    2005-01-01

    Based on D Brynn Hibbert''s lectures on data analysis to undergraduates and graduate students, this book covers topics including measurements, means and confidence intervals, hypothesis testing, analysis of variance, and calibration models. It is meant as an entry level book targeted at learning and teaching undergraduate data analysis.

  20. Bayesian Mediation Analysis

    Science.gov (United States)

    Yuan, Ying; MacKinnon, David P.

    2009-01-01

    In this article, we propose Bayesian analysis of mediation effects. Compared with conventional frequentist mediation analysis, the Bayesian approach has several advantages. First, it allows researchers to incorporate prior information into the mediation analysis, thus potentially improving the efficiency of estimates. Second, under the Bayesian…

  1. Strategic Analysis Overview

    Science.gov (United States)

    Cirillo, William M.; Earle, Kevin D.; Goodliff, Kandyce E.; Reeves, J. D.; Stromgren, Chel; Andraschko, Mark R.; Merrill, R. Gabe

    2008-01-01

    NASA s Constellation Program employs a strategic analysis methodology in providing an integrated analysis capability of Lunar exploration scenarios and to support strategic decision-making regarding those scenarios. The strategic analysis methodology integrates the assessment of the major contributors to strategic objective satisfaction performance, affordability, and risk and captures the linkages and feedbacks between all three components. Strategic analysis supports strategic decision making by senior management through comparable analysis of alternative strategies, provision of a consistent set of high level value metrics, and the enabling of cost-benefit analysis. The tools developed to implement the strategic analysis methodology are not element design and sizing tools. Rather, these models evaluate strategic performance using predefined elements, imported into a library from expert-driven design/sizing tools or expert analysis. Specific components of the strategic analysis tool set include scenario definition, requirements generation, mission manifesting, scenario lifecycle costing, crew time analysis, objective satisfaction benefit, risk analysis, and probabilistic evaluation. Results from all components of strategic analysis are evaluated a set of pre-defined figures of merit (FOMs). These FOMs capture the high-level strategic characteristics of all scenarios and facilitate direct comparison of options. The strategic analysis methodology that is described in this paper has previously been applied to the Space Shuttle and International Space Station Programs and is now being used to support the development of the baseline Constellation Program lunar architecture. This paper will present an overview of the strategic analysis methodology and will present sample results from the application of the strategic analysis methodology to the Constellation Program lunar architecture.

  2. Foundations of mathematical analysis

    CERN Document Server

    Johnsonbaugh, Richard

    2010-01-01

    This classroom-tested volume offers a definitive look at modern analysis, with views of applications to statistics, numerical analysis, Fourier series, differential equations, mathematical analysis, and functional analysis. Upper-level undergraduate students with a background in calculus will benefit from its teachings, along with beginning graduate students seeking a firm grounding in modern analysis. A self-contained text, it presents the necessary background on the limit concept, and the first seven chapters could constitute a one-semester introduction to limits. Subsequent chapters discuss

  3. Multivariate analysis with LISREL

    CERN Document Server

    Jöreskog, Karl G; Y Wallentin, Fan

    2016-01-01

    This book traces the theory and methodology of multivariate statistical analysis and shows how it can be conducted in practice using the LISREL computer program. It presents not only the typical uses of LISREL, such as confirmatory factor analysis and structural equation models, but also several other multivariate analysis topics, including regression (univariate, multivariate, censored, logistic, and probit), generalized linear models, multilevel analysis, and principal component analysis. It provides numerous examples from several disciplines and discusses and interprets the results, illustrated with sections of output from the LISREL program, in the context of the example. The book is intended for masters and PhD students and researchers in the social, behavioral, economic and many other sciences who require a basic understanding of multivariate statistical theory and methods for their analysis of multivariate data. It can also be used as a textbook on various topics of multivariate statistical analysis.

  4. http Log Analysis

    DEFF Research Database (Denmark)

    Bøving, Kristian Billeskov; Simonsen, Jesper

    2004-01-01

    This article documents how log analysis can inform qualitative studies concerning the usage of web-based information systems (WIS). No prior research has used http log files as data to study collaboration between multiple users in organisational settings. We investigate how to perform http log...... analysis; what http log analysis says about the nature of collaborative WIS use; and how results from http log analysis may support other data collection methods such as surveys, interviews, and observation. The analysis of log files initially lends itself to research designs, which serve to test...... hypotheses using a quantitative methodology. We show that http log analysis can also be valuable in qualitative research such as case studies. The results from http log analysis can be triangulated with other data sources and for example serve as a means of supporting the interpretation of interview data...

  5. The ATLAS Analysis Model

    CERN Multimedia

    Amir Farbin

    The ATLAS Analysis Model is a continually developing vision of how to reconcile physics analysis requirements with the ATLAS offline software and computing model constraints. In the past year this vision has influenced the evolution of the ATLAS Event Data Model, the Athena software framework, and physics analysis tools. These developments, along with the October Analysis Model Workshop and the planning for CSC analyses have led to a rapid refinement of the ATLAS Analysis Model in the past few months. This article introduces some of the relevant issues and presents the current vision of the future ATLAS Analysis Model. Event Data Model The ATLAS Event Data Model (EDM) consists of several levels of details, each targeted for a specific set of tasks. For example the Event Summary Data (ESD) stores calorimeter cells and tracking system hits thereby permitting many calibration and alignment tasks, but will be only accessible at particular computing sites with potentially large latency. In contrast, the Analysis...

  6. Social Set Analysis

    DEFF Research Database (Denmark)

    Vatrapu, Ravi; Mukkamala, Raghava Rao; Hussain, Abid

    2016-01-01

    Current analytical approaches in computational social science can be characterized by four dominant paradigms: text analysis (information extraction and classification), social network analysis (graph theory), social complexity analysis (complex systems science), and social simulations (cellular...... this limitation, based on the sociology of associations and the mathematics of set theory, this paper presents a new approach to big data analytics called social set analysis. Social set analysis consists of a generative framework for the philosophies of computational social science, theory of social data...... analysis, crisp set-theoretical interaction analysis, and event-studies-oriented set-theoretical visualizations. Implications for big data analytics, current limitations of the set-theoretical approach, and future directions are outlined....

  7. Cost benefit analysis cost effectiveness analysis

    International Nuclear Information System (INIS)

    Lombard, J.

    1986-09-01

    The comparison of various protection options in order to determine which is the best compromise between cost of protection and residual risk is the purpose of the ALARA procedure. The use of decision-aiding techniques is valuable as an aid to selection procedures. The purpose of this study is to introduce two rather simple and well known decision aiding techniques: the cost-effectiveness analysis and the cost-benefit analysis. These two techniques are relevant for the great part of ALARA decisions which need the use of a quantitative technique. The study is based on an hypothetical case of 10 protection options. Four methods are applied to the data

  8. NASA trend analysis procedures

    Science.gov (United States)

    1993-01-01

    This publication is primarily intended for use by NASA personnel engaged in managing or implementing trend analysis programs. 'Trend analysis' refers to the observation of current activity in the context of the past in order to infer the expected level of future activity. NASA trend analysis was divided into 5 categories: problem, performance, supportability, programmatic, and reliability. Problem trend analysis uncovers multiple occurrences of historical hardware or software problems or failures in order to focus future corrective action. Performance trend analysis observes changing levels of real-time or historical flight vehicle performance parameters such as temperatures, pressures, and flow rates as compared to specification or 'safe' limits. Supportability trend analysis assesses the adequacy of the spaceflight logistics system; example indicators are repair-turn-around time and parts stockage levels. Programmatic trend analysis uses quantitative indicators to evaluate the 'health' of NASA programs of all types. Finally, reliability trend analysis attempts to evaluate the growth of system reliability based on a decreasing rate of occurrence of hardware problems over time. Procedures for conducting all five types of trend analysis are provided in this publication, prepared through the joint efforts of the NASA Trend Analysis Working Group.

  9. Fundamentals of functional analysis

    CERN Document Server

    Farenick, Douglas

    2016-01-01

    This book provides a unique path for graduate or advanced undergraduate students to begin studying the rich subject of functional analysis with fewer prerequisites than is normally required. The text begins with a self-contained and highly efficient introduction to topology and measure theory, which focuses on the essential notions required for the study of functional analysis, and which are often buried within full-length overviews of the subjects. This is particularly useful for those in applied mathematics, engineering, or physics who need to have a firm grasp of functional analysis, but not necessarily some of the more abstruse aspects of topology and measure theory normally encountered. The reader is assumed to only have knowledge of basic real analysis, complex analysis, and algebra. The latter part of the text provides an outstanding treatment of Banach space theory and operator theory, covering topics not usually found together in other books on functional analysis. Written in a clear, concise manner,...

  10. Data analysis in astronomy

    International Nuclear Information System (INIS)

    Di Gesu, V.; Crane, P.; Friedman, J.H.; Levialdi, S.; Scarsi, L.

    1985-01-01

    This book presents information on the following topics: the data analysis facilities that astronomers want; time analysis in astronomy; tools for periodicity searches; graphical methods of exploratory data analysis; multivariate statistics to analyze extraterrestrial particles from the ocean floor; application of bootstrap sampling in gamma-ray astronomy; an automated method for velocity field analysis; panel discussion on data analysis trends in x-ray and gamma-ray astronomy; the Groningen image processing system; astronomical input to image processing - astronomical output from image processing; 2-D photometry; spectrometry; time dependent analysis; solar image processing with the Clark Lake Radioheliograph; steps toward parallel processing; new architectures for image processing; data structures and languages in support of parallel image processing for astronomy; and morphology and probability in image processing

  11. Computational Music Analysis

    DEFF Research Database (Denmark)

    This book provides an in-depth introduction and overview of current research in computational music analysis. Its seventeen chapters, written by leading researchers, collectively represent the diversity as well as the technical and philosophical sophistication of the work being done today...... on well-established theories in music theory and analysis, such as Forte's pitch-class set theory, Schenkerian analysis, the methods of semiotic analysis developed by Ruwet and Nattiez, and Lerdahl and Jackendoff's Generative Theory of Tonal Music. The book is divided into six parts, covering...... music analysis, the book provides an invaluable resource for researchers, teachers and students in music theory and analysis, computer science, music information retrieval and related disciplines. It also provides a state-of-the-art reference for practitioners in the music technology industry....

  12. Sparse Exploratory Factor Analysis.

    Science.gov (United States)

    Trendafilov, Nickolay T; Fontanella, Sara; Adachi, Kohei

    2017-07-13

    Sparse principal component analysis is a very active research area in the last decade. It produces component loadings with many zero entries which facilitates their interpretation and helps avoid redundant variables. The classic factor analysis is another popular dimension reduction technique which shares similar interpretation problems and could greatly benefit from sparse solutions. Unfortunately, there are very few works considering sparse versions of the classic factor analysis. Our goal is to contribute further in this direction. We revisit the most popular procedures for exploratory factor analysis, maximum likelihood and least squares. Sparse factor loadings are obtained for them by, first, adopting a special reparameterization and, second, by introducing additional [Formula: see text]-norm penalties into the standard factor analysis problems. As a result, we propose sparse versions of the major factor analysis procedures. We illustrate the developed algorithms on well-known psychometric problems. Our sparse solutions are critically compared to ones obtained by other existing methods.

  13. Analysis apparatus and method of analysis

    International Nuclear Information System (INIS)

    1976-01-01

    A continuous streaming method developed for the excution of immunoassays is described in this patent. In addition, a suitable apparatus for the method was developed whereby magnetic particles are automatically employed for the consecutive analysis of a series of liquid samples via the RIA technique

  14. Static Analysis Numerical Algorithms

    Science.gov (United States)

    2016-04-01

    STATIC ANALYSIS OF NUMERICAL ALGORITHMS KESTREL TECHNOLOGY, LLC APRIL 2016 FINAL TECHNICAL REPORT APPROVED FOR PUBLIC RELEASE; DISTRIBUTION...3. DATES COVERED (From - To) NOV 2013 – NOV 2015 4. TITLE AND SUBTITLE STATIC ANALYSIS OF NUMERICAL ALGORITHMS 5a. CONTRACT NUMBER FA8750-14-C...and Honeywell Aerospace Advanced Technology to combine model-based development of complex avionics control software with static analysis of the

  15. Emission spectrochemical analysis

    International Nuclear Information System (INIS)

    Rives, R.D.; Bruks, R.R.

    1983-01-01

    The emission spectrochemical method of analysis based on the fact that atoms of elements can be excited in the electric arc or in the laser beam and will emit radiation with characteristic wave lengths is considered. The review contains the data on spectrochemical analysis, of liquids geological materials, scheme of laser microprobe. The main characteristics of emission spectroscopy, atomic absorption spectroscopy and X-ray fluorescent analysis, are aeneralized

  16. Mastering Clojure data analysis

    CERN Document Server

    Rochester, Eric

    2014-01-01

    This book consists of a practical, example-oriented approach that aims to help you learn how to use Clojure for data analysis quickly and efficiently.This book is great for those who have experience with Clojure and who need to use it to perform data analysis. This book will also be hugely beneficial for readers with basic experience in data analysis and statistics.

  17. The ATLAS Analysis Architecture

    International Nuclear Information System (INIS)

    Cranmer, K.S.

    2008-01-01

    We present an overview of the ATLAS analysis architecture including the relevant aspects of the computing model and the major architectural aspects of the Athena framework. Emphasis will be given to the interplay between the analysis use cases and the technical aspects of the architecture including the design of the event data model, transient-persistent separation, data reduction strategies, analysis tools, and ROOT interoperability

  18. Stochastic Analysis 2010

    CERN Document Server

    Crisan, Dan

    2011-01-01

    "Stochastic Analysis" aims to provide mathematical tools to describe and model high dimensional random systems. Such tools arise in the study of Stochastic Differential Equations and Stochastic Partial Differential Equations, Infinite Dimensional Stochastic Geometry, Random Media and Interacting Particle Systems, Super-processes, Stochastic Filtering, Mathematical Finance, etc. Stochastic Analysis has emerged as a core area of late 20th century Mathematics and is currently undergoing a rapid scientific development. The special volume "Stochastic Analysis 2010" provides a sa

  19. Introduction to analysis

    CERN Document Server

    Gaughan, Edward D

    2009-01-01

    Introduction to Analysis is designed to bridge the gap between the intuitive calculus usually offered at the undergraduate level and the sophisticated analysis courses the student encounters at the graduate level. In this book the student is given the vocabulary and facts necessary for further study in analysis. The course for which it is designed is usually offered at the junior level, and it is assumed that the student has little or no previous experience with proofs in analysis. A considerable amount of time is spent motivating the theorems and proofs and developing the reader's intuition.

  20. Space Weather Analysis

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Space Weather Analysis archives are model output of ionospheric, thermospheric and magnetospheric particle populations, energies and electrodynamics

  1. Textile Technology Analysis Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The Textile Analysis Labis built for evaluating and characterizing the physical properties of an array of textile materials, but specifically those used in aircrew...

  2. Risk analysis methodology survey

    Science.gov (United States)

    Batson, Robert G.

    1987-01-01

    NASA regulations require that formal risk analysis be performed on a program at each of several milestones as it moves toward full-scale development. Program risk analysis is discussed as a systems analysis approach, an iterative process (identification, assessment, management), and a collection of techniques. These techniques, which range from simple to complex network-based simulation were surveyed. A Program Risk Analysis Handbook was prepared in order to provide both analyst and manager with a guide for selection of the most appropriate technique.

  3. Thermogravimetric Analysis Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — At NETL’s Thermogravimetric Analysis Laboratory in Morgantown, WV, researchers study how chemical looping combustion (CLC) can be applied to fossil energy systems....

  4. Sensitivity and uncertainty analysis

    CERN Document Server

    Cacuci, Dan G; Navon, Ionel Michael

    2005-01-01

    As computer-assisted modeling and analysis of physical processes have continued to grow and diversify, sensitivity and uncertainty analyses have become indispensable scientific tools. Sensitivity and Uncertainty Analysis. Volume I: Theory focused on the mathematical underpinnings of two important methods for such analyses: the Adjoint Sensitivity Analysis Procedure and the Global Adjoint Sensitivity Analysis Procedure. This volume concentrates on the practical aspects of performing these analyses for large-scale systems. The applications addressed include two-phase flow problems, a radiative c

  5. International Market Analysis

    DEFF Research Database (Denmark)

    Sørensen, Olav Jull

    2009-01-01

    The review presents the book International Market Analysis: Theories and Methods, written by John Kuiada, professor at Centre of International Business, Department of Business Studies, Aalborg University. The book is refreshingly new in its way of looking at a classical problem. It looks at market...... analysis from the point of vie of ways of thinking about markets. Furthermore, the book includes the concept of learning in the analysis of markets og how the way we understand business reality influneces our choice of methodology for market analysis....

  6. Machine Fault Signature Analysis

    Directory of Open Access Journals (Sweden)

    Pratesh Jayaswal

    2008-01-01

    Full Text Available The objective of this paper is to present recent developments in the field of machine fault signature analysis with particular regard to vibration analysis. The different types of faults that can be identified from the vibration signature analysis are, for example, gear fault, rolling contact bearing fault, journal bearing fault, flexible coupling faults, and electrical machine fault. It is not the intention of the authors to attempt to provide a detailed coverage of all the faults while detailed consideration is given to the subject of the rolling element bearing fault signature analysis.

  7. Analysis of food contaminants

    National Research Council Canada - National Science Library

    Gilbert, John

    1984-01-01

    ... quantification methods used in the analysis of mycotoxins in foods - Confirmation and quantification of trace organic food contaminants by mass spectrometry-selected ion monitoring - Chemiluminescence...

  8. Geospatial Data Analysis Facility

    Data.gov (United States)

    Federal Laboratory Consortium — Geospatial application development, location-based services, spatial modeling, and spatial analysis are examples of the many research applications that this facility...

  9. Gabor Analysis for Imaging

    DEFF Research Database (Denmark)

    Christensen, Ole; Feichtinger, Hans G.; Paukner, Stephan

    2015-01-01

    In contrast to classical Fourier analysis, time–frequency analysis is concerned with localized Fourier transforms. Gabor analysis is an important branch of time–frequency analysis. Although significantly different, it shares with the wavelet transform methods the ability to describe the smoothness......, it characterizes a function by its transform over phase space, which is the time–frequency plane (TF-plane) in a musical context or the location–wave-number domain in the context of image processing. Since the transition from the signal domain to the phase space domain introduces an enormous amount of data...

  10. Circuit analysis with Multisim

    CERN Document Server

    Baez-Lopez, David

    2011-01-01

    This book is concerned with circuit simulation using National Instruments Multisim. It focuses on the use and comprehension of the working techniques for electrical and electronic circuit simulation. The first chapters are devoted to basic circuit analysis.It starts by describing in detail how to perform a DC analysis using only resistors and independent and controlled sources. Then, it introduces capacitors and inductors to make a transient analysis. In the case of transient analysis, it is possible to have an initial condition either in the capacitor voltage or in the inductor current, or bo

  11. Chemical Analysis Facility

    Data.gov (United States)

    Federal Laboratory Consortium — FUNCTION: Uses state-of-the-art instrumentation for qualitative and quantitative analysis of organic and inorganic compounds, and biomolecules from gas, liquid, and...

  12. Chemical Security Analysis Center

    Data.gov (United States)

    Federal Laboratory Consortium — In 2006, by Presidential Directive, DHS established the Chemical Security Analysis Center (CSAC) to identify and assess chemical threats and vulnerabilities in the...

  13. Risk Analysis of Marine Structures

    DEFF Research Database (Denmark)

    Hansen, Peter Friis

    1998-01-01

    Basic concepts of risk analysis is introduced. Formulation and analysis of fault and event trees are treated.......Basic concepts of risk analysis is introduced. Formulation and analysis of fault and event trees are treated....

  14. Electric field analysis

    CERN Document Server

    Chakravorti, Sivaji

    2015-01-01

    This book prepares newcomers to dive into the realm of electric field analysis. The book details why one should perform electric field analysis and what are its practical implications. It emphasizes both the fundamentals and modern computational methods of electric machines. The book covers practical applications of the numerical methods in high voltage equipment, including transmission lines, power transformers, cables, and gas insulated systems.

  15. SWOT ANALYSIS - CHINESE PETROLEUM

    Directory of Open Access Journals (Sweden)

    Chunlan Wang

    2014-01-01

    Full Text Available This article was written in early December 2013,combined with the historical development andthe latest data on the Chinese Petroleum carried SWOT- analysis. This paper discusses corporate resources, cost, management and external factorssuch as the political environment and the marketsupply and demand, conducted a comprehensiveand profound analysis.

  16. Numerical Limit Analysis:

    DEFF Research Database (Denmark)

    Damkilde, Lars

    2007-01-01

    Limit State analysis has a long history and many prominent researchers have contributed. The theoretical foundation is based on the upper- and lower-bound theorems which give a very comprehensive and elegant formulation on complicated physical problems. In the pre-computer age Limit State analysis...... also enabled engineers to solve practical problems within reinforced concrete, steel structures and geotechnics....

  17. Longitudinal Meta-analysis

    NARCIS (Netherlands)

    Hox, J.J.; Maas, C.J.M.; Lensvelt-Mulders, G.J.L.M.

    2004-01-01

    The goal of meta-analysis is to integrate the research results of a number of studies on a specific topic. Characteristic for meta-analysis is that in general only the summary statistics of the studies are used and not the original data. When the published research results to be integrated

  18. Spool assembly support analysis

    International Nuclear Information System (INIS)

    Norman, B.F.

    1994-01-01

    This document provides the wind/seismic analysis and evaluation for the pump pit spool assemblies. Hand calculations were used for the analysis. UBC, AISC, and load factors were used in this evaluation. The results show that the actual loads are under the allowable loads and all requirements are met

  19. Northern blotting analysis

    DEFF Research Database (Denmark)

    Josefsen, Knud; Nielsen, Henrik

    2011-01-01

    Northern blotting analysis is a classical method for analysis of the size and steady-state level of a specific RNA in a complex sample. In short, the RNA is size-fractionated by gel electrophoresis and transferred by blotting onto a membrane to which the RNA is covalently bound. Then, the membrane...... the gap to the more laborious nuclease protection experiments....

  20. Beyond sensitivity analysis

    DEFF Research Database (Denmark)

    Lund, Henrik; Sorknæs, Peter; Mathiesen, Brian Vad

    2018-01-01

    point of view, the typical way of handling this challenge has been to predict future prices as accurately as possible and then conduct a sensitivity analysis. This paper includes a historical analysis of such predictions, leading to the conclusion that they are almost always wrong. Not only...

  1. Enabling interdisciplinary analysis

    Science.gov (United States)

    L. M. Reid

    1996-01-01

    'New requirements for evaluating environmental conditions in the Pacific Northwest have led to increased demands for interdisciplinary analysis of complex environmental problems. Procedures for watershed analysis have been developed for use on public and private lands in Washington State (Washington Forest Practices Board 1993) and for federal lands in the Pacific...

  2. Spectroscopic analysis and control

    Energy Technology Data Exchange (ETDEWEB)

    Tate; , James D.; Reed, Christopher J.; Domke, Christopher H.; Le, Linh; Seasholtz, Mary Beth; Weber, Andy; Lipp, Charles

    2017-04-18

    Apparatus for spectroscopic analysis which includes a tunable diode laser spectrometer having a digital output signal and a digital computer for receiving the digital output signal from the spectrometer, the digital computer programmed to process the digital output signal using a multivariate regression algorithm. In addition, a spectroscopic method of analysis using such apparatus. Finally, a method for controlling an ethylene cracker hydrogenator.

  3. Activation analysis. Detection limits

    International Nuclear Information System (INIS)

    Revel, G.

    1999-01-01

    Numerical data and limits of detection related to the four irradiation modes, often used in activation analysis (reactor neutrons, 14 MeV neutrons, photon gamma and charged particles) are presented here. The technical presentation of the activation analysis is detailed in the paper P 2565 of Techniques de l'Ingenieur. (A.L.B.)

  4. Advanced Analysis Environments - Summary

    International Nuclear Information System (INIS)

    Panacek, Suzanne

    2001-01-01

    This is a summary of the panel discussion on Advanced Analysis Environments. Rene Brun, Tony Johnson, and Lassi Tuura shared their insights about the trends and challenges in analysis environments. This paper contains the initial questions, a summary of the speakers' presentation, and the questions asked by the audience

  5. Analysis of Design Documentation

    DEFF Research Database (Denmark)

    Hansen, Claus Thorp

    1998-01-01

    has been established where we seek to identify useful design work patterns by retrospective analyses of documentation created during design projects. This paper describes the analysis method, a tentatively defined metric to evaluate identified work patterns, and presents results from the first...... analysis accomplished....

  6. FOOD RISK ANALYSIS

    Science.gov (United States)

    Food risk analysis is a holistic approach to food safety because it considers all aspects of the problem. Risk assessment modeling is the foundation of food risk analysis. Proper design and simulation of the risk assessment model is important to properly predict and control risk. Because of knowl...

  7. Marketing research cluster analysis

    Directory of Open Access Journals (Sweden)

    Marić Nebojša

    2002-01-01

    Full Text Available One area of applications of cluster analysis in marketing is identification of groups of cities and towns with similar demographic profiles. This paper considers main aspects of cluster analysis by an example of clustering 12 cities with the use of Minitab software.

  8. Interaction Analysis and Supervision.

    Science.gov (United States)

    Amidon, Edmund

    This paper describes a model that uses interaction analysis as a tool to provide feedback to a teacher in a microteaching situation. The author explains how interaction analysis can be used for teacher improvement, describes the category system used in the model, the data collection methods used, and the feedback techniques found in the model. (JF)

  9. Zen and Behavior Analysis

    Science.gov (United States)

    Bass, Roger

    2010-01-01

    Zen's challenge for behavior analysis is to explain a repertoire that renders analysis itself meaningless--a result following not from scientific or philosophical arguments but rather from a unique verbal history generated by Zen's methods. Untying Zen's verbal knots suggests how meditation's and koans' effects on verbal behavior contribute to…

  10. Statistical data analysis

    International Nuclear Information System (INIS)

    Hahn, A.A.

    1994-11-01

    The complexity of instrumentation sometimes requires data analysis to be done before the result is presented to the control room. This tutorial reviews some of the theoretical assumptions underlying the more popular forms of data analysis and presents simple examples to illuminate the advantages and hazards of different techniques

  11. Qualitative Content Analysis

    OpenAIRE

    Satu Elo; Maria Kääriäinen; Outi Kanste; Tarja Pölkki; Kati Utriainen; Helvi Kyngäs

    2014-01-01

    Qualitative content analysis is commonly used for analyzing qualitative data. However, few articles have examined the trustworthiness of its use in nursing science studies. The trustworthiness of qualitative content analysis is often presented by using terms such as credibility, dependability, conformability, transferability, and authenticity. This article focuses on trustworthiness based on a review of previous studie...

  12. Qualitative Content Analysis

    Directory of Open Access Journals (Sweden)

    Satu Elo

    2014-02-01

    Full Text Available Qualitative content analysis is commonly used for analyzing qualitative data. However, few articles have examined the trustworthiness of its use in nursing science studies. The trustworthiness of qualitative content analysis is often presented by using terms such as credibility, dependability, conformability, transferability, and authenticity. This article focuses on trustworthiness based on a review of previous studies, our own experiences, and methodological textbooks. Trustworthiness was described for the main qualitative content analysis phases from data collection to reporting of the results. We concluded that it is important to scrutinize the trustworthiness of every phase of the analysis process, including the preparation, organization, and reporting of results. Together, these phases should give a reader a clear indication of the overall trustworthiness of the study. Based on our findings, we compiled a checklist for researchers attempting to improve the trustworthiness of a content analysis study. The discussion in this article helps to clarify how content analysis should be reported in a valid and understandable manner, which would be of particular benefit to reviewers of scientific articles. Furthermore, we discuss that it is often difficult to evaluate the trustworthiness of qualitative content analysis studies because of defective data collection method description and/or analysis description.

  13. Interactive Controls Analysis (INCA)

    Science.gov (United States)

    Bauer, Frank H.

    1989-01-01

    Version 3.12 of INCA provides user-friendly environment for design and analysis of linear control systems. System configuration and parameters easily adjusted, enabling INCA user to create compensation networks and perform sensitivity analysis in convenient manner. Full complement of graphical routines makes output easy to understand. Written in Pascal and FORTRAN.

  14. Towards Cognitive Component Analysis

    DEFF Research Database (Denmark)

    Hansen, Lars Kai; Ahrendt, Peter; Larsen, Jan

    2005-01-01

    Cognitive component analysis (COCA) is here defined as the process of unsupervised grouping of data such that the ensuing group structure is well-aligned with that resulting from human cognitive activity. We have earlier demonstrated that independent components analysis is relevant for representi...

  15. Northern blotting analysis

    DEFF Research Database (Denmark)

    Josefsen, Knud; Nielsen, Henrik

    2011-01-01

    Northern blotting analysis is a classical method for analysis of the size and steady-state level of a specific RNA in a complex sample. In short, the RNA is size-fractionated by gel electrophoresis and transferred by blotting onto a membrane to which the RNA is covalently bound. Then, the membran...

  16. Proximate Analysis of Coal

    Science.gov (United States)

    Donahue, Craig J.; Rais, Elizabeth A.

    2009-01-01

    This lab experiment illustrates the use of thermogravimetric analysis (TGA) to perform proximate analysis on a series of coal samples of different rank. Peat and coke are also examined. A total of four exercises are described. These are dry exercises as students interpret previously recorded scans. The weight percent moisture, volatile matter,…

  17. Systems engineering and analysis

    CERN Document Server

    Blanchard, Benjamin S

    2010-01-01

    For senior-level undergraduate and first and second year graduate systems engineering and related courses. A total life-cycle approach to systems and their analysis. This practical introduction to systems engineering and analysis provides the concepts, methodologies, models, and tools needed to understand and implement a total life-cycle approach to systems and their analysis. The authors focus first on the process of bringing systems into being--beginning with the identification of a need and extending that need through requirements determination, functional analysis and allocation, design synthesis, evaluation, and validation, operation and support, phase-out, and disposal. Next, the authors discuss the improvement of systems currently in being, showing that by employing the iterative process of analysis, evaluation, feedback, and modification, most systems in existence can be improved in their affordability, effectiveness, and stakeholder satisfaction.

  18. Robust multivariate analysis

    CERN Document Server

    J Olive, David

    2017-01-01

    This text presents methods that are robust to the assumption of a multivariate normal distribution or methods that are robust to certain types of outliers. Instead of using exact theory based on the multivariate normal distribution, the simpler and more applicable large sample theory is given.  The text develops among the first practical robust regression and robust multivariate location and dispersion estimators backed by theory.   The robust techniques  are illustrated for methods such as principal component analysis, canonical correlation analysis, and factor analysis.  A simple way to bootstrap confidence regions is also provided. Much of the research on robust multivariate analysis in this book is being published for the first time. The text is suitable for a first course in Multivariate Statistical Analysis or a first course in Robust Statistics. This graduate text is also useful for people who are familiar with the traditional multivariate topics, but want to know more about handling data sets with...

  19. Essential real analysis

    CERN Document Server

    Field, Michael

    2017-01-01

    This book provides a rigorous introduction to the techniques and results of real analysis, metric spaces and multivariate differentiation, suitable for undergraduate courses. Starting from the very foundations of analysis, it offers a complete first course in real analysis, including topics rarely found in such detail in an undergraduate textbook such as the construction of non-analytic smooth functions, applications of the Euler-Maclaurin formula to estimates, and fractal geometry.  Drawing on the author’s extensive teaching and research experience, the exposition is guided by carefully chosen examples and counter-examples, with the emphasis placed on the key ideas underlying the theory. Much of the content is informed by its applicability: Fourier analysis is developed to the point where it can be rigorously applied to partial differential equations or computation, and the theory of metric spaces includes applications to ordinary differential equations and fractals. Essential Real Analysis will appeal t...

  20. From analysis to surface

    DEFF Research Database (Denmark)

    Bemman, Brian; Meredith, David

    In recent years, a significant body of research has focused on developing algorithms for computing analyses of mu- sical works automatically from encodings of these works' surfaces [3,4,7,10,11]. The quality of the output of such analysis algorithms is typically evaluated by comparing it with a “......In recent years, a significant body of research has focused on developing algorithms for computing analyses of mu- sical works automatically from encodings of these works' surfaces [3,4,7,10,11]. The quality of the output of such analysis algorithms is typically evaluated by comparing...... an effective (i.e., comput- able), correct and complete description of some aspect of the structure of the music. Generating the surface struc- ture of a piece from an analysis in this manner serves as a proof of the analysis' correctness, effectiveness and com- pleteness. We present a reductive analysis...

  1. Functional data analysis

    CERN Document Server

    Ramsay, J O

    1997-01-01

    Scientists today collect samples of curves and other functional observations. This monograph presents many ideas and techniques for such data. Included are expressions in the functional domain of such classics as linear regression, principal components analysis, linear modelling, and canonical correlation analysis, as well as specifically functional techniques such as curve registration and principal differential analysis. Data arising in real applications are used throughout for both motivation and illustration, showing how functional approaches allow us to see new things, especially by exploiting the smoothness of the processes generating the data. The data sets exemplify the wide scope of functional data analysis; they are drwan from growth analysis, meterology, biomechanics, equine science, economics, and medicine. The book presents novel statistical technology while keeping the mathematical level widely accessible. It is designed to appeal to students, to applied data analysts, and to experienced researc...

  2. Java Analysis Studio

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Anthony S

    1998-10-23

    Java Analysis Studio is a desktop data analysis application aimed primarily at offline analysis of high-energy physics data. The goal is to make the application independent of any particular data format, so that it can be used to analyze data from any experiment. The application features a rich graphical user interface (GUI) aimed at making the program easy to learn and use, but which at the same time allows the user to perform arbitrarily complex data analysis tasks by writing analysis modules in Java. The application can be used either as a standalone application, or as a client for a remote Java Data Server. The client-server mechanism is targeted particularly at allowing remote users to access large data samples stored on a central data center in a natural and efficient way.

  3. Data analysis workbench

    International Nuclear Information System (INIS)

    Goetz, A.; Gerring, M.; Svensson, O.; Brockhauser, S.

    2012-01-01

    Data Analysis Workbench (DAWB) is a new software tool being developed at the ESRF. Its goal is to provide a tool for both online data analysis which can be used on the beamlines and for offline data analysis which users can use during experiments or take home. The tool includes support for data visualization and work-flows. work-flows allow algorithms which exploit parallel architectures to be designed from existing high level modules for data analysis in combination with data collection. The workbench uses Passerelle as the work-flow engine and EDNA plug-ins for data analysis. Actors talking to Tango are used for sending commands to a limited set of hardware to start existing data collection algorithms. A Tango server allows work-flows to be executed from existing applications. There are scripting interfaces to Python, Javascript and SPEC. The current state at the ESRF is the workbench is in test on a selected number of beamlines. (authors)

  4. K Basin safety analysis

    International Nuclear Information System (INIS)

    Porten, D.R.; Crowe, R.D.

    1994-01-01

    The purpose of this accident safety analysis is to document in detail, analyses whose results were reported in summary form in the K Basins Safety Analysis Report WHC-SD-SNF-SAR-001. The safety analysis addressed the potential for release of radioactive and non-radioactive hazardous material located in the K Basins and their supporting facilities. The safety analysis covers the hazards associated with normal K Basin fuel storage and handling operations, fuel encapsulation, sludge encapsulation, and canister clean-up and disposal. After a review of the Criticality Safety Evaluation of the K Basin activities, the following postulated events were evaluated: Crane failure and casks dropped into loadout pit; Design basis earthquake; Hypothetical loss of basin water accident analysis; Combustion of uranium fuel following dryout; Crane failure and cask dropped onto floor of transfer area; Spent ion exchange shipment for burial; Hydrogen deflagration in ion exchange modules and filters; Release of Chlorine; Power availability and reliability; and Ashfall

  5. Gait analysis: clinical facts.

    Science.gov (United States)

    Baker, Richard; Esquenazi, Alberto; Benedetti, Maria G; Desloovere, Kaat

    2016-08-01

    Gait analysis is a well-established tool for the quantitative assessment of gait disturbances providing functional diagnosis, assessment for treatment planning, and monitoring of disease progress. There is a large volume of literature on the research use of gait analysis, but evidence on its clinical routine use supports a favorable cost-benefit ratio in a limited number of conditions. Initially gait analysis was introduced to clinical practice to improve the management of children with cerebral palsy. However, there is good evidence to extend its use to patients with various upper motor neuron diseases, and to lower limb amputation. Thereby, the methodology for properly conducting and interpreting the exam is of paramount relevance. Appropriateness of gait analysis prescription and reliability of data obtained are required in the clinical environment. This paper provides an overview on guidelines for managing a clinical gait analysis service and on the principal clinical domains of its application: cerebral palsy, stroke, traumatic brain injury and lower limb amputation.

  6. Is activation analysis still active?

    International Nuclear Information System (INIS)

    Chai Zhifang

    2001-01-01

    This paper reviews some aspects of neutron activation analysis (NAA), covering instrumental neutron activation analysis (INAA), k 0 method, prompt gamma-ray neutron activation analysis (PGNAA), radiochemical neutron activation analysis (RNAA) and molecular activation analysis (MAA). The comparison of neutron activation analysis with other analytical techniques are also made. (author)

  7. Hazard Analysis Database Report

    Energy Technology Data Exchange (ETDEWEB)

    GAULT, G.W.

    1999-10-13

    The Hazard Analysis Database was developed in conjunction with the hazard analysis activities conducted in accordance with DOE-STD-3009-94, Preparation Guide for US Department of Energy Nonreactor Nuclear Facility Safety Analysis Reports, for the Tank Waste Remediation System (TWRS) Final Safety Analysis Report (FSAR). The FSAR is part of the approved TWRS Authorization Basis (AB). This document describes, identifies, and defines the contents and structure of the TWRS FSAR Hazard Analysis Database and documents the configuration control changes made to the database. The TWRS Hazard Analysis Database contains the collection of information generated during the initial hazard evaluations and the subsequent hazard and accident analysis activities. The database supports the preparation of Chapters 3,4, and 5 of the TWRS FSAR and the USQ process and consists of two major, interrelated data sets: (1) Hazard Evaluation Database--Data from the results of the hazard evaluations; and (2) Hazard Topography Database--Data from the system familiarization and hazard identification.

  8. Containment vessel stability analysis

    International Nuclear Information System (INIS)

    Harstead, G.A.; Morris, N.F.; Unsal, A.I.

    1983-01-01

    The stability analysis for a steel containment shell is presented herein. The containment is a freestanding shell consisting of a vertical cylinder with a hemispherical dome. It is stiffened by large ring stiffeners and relatively small longitudinal stiffeners. The containment vessel is subjected to both static and dynamic loads which can cause buckling. These loads must be combined prior to their use in a stability analysis. The buckling loads were computed with the aid of the ASME Code case N-284 used in conjunction with general purpose computer codes and in-house programs. The equations contained in the Code case were used to compute the knockdown factors due to shell imperfections. After these knockdown factors were applied to the critical stress states determined by freezing the maximum dynamic stresses and combining them with other static stresses, a linear bifurcation analysis was carried out with the aid of the BOSOR4 program. Since the containment shell contained large penetrations, the Code case had to be supplemented by a local buckling analysis of the shell area surrounding the largest penetration. This analysis was carried out with the aid of the NASTRAN program. Although the factor of safety against buckling obtained in this analysis was satisfactory, it is claimed that the use of the Code case knockdown factors are unduly conservative when applied to the analysis of buckling around penetrations. (orig.)

  9. Analysis of monazite samples

    International Nuclear Information System (INIS)

    Kartiwa Sumadi; Yayah Rohayati

    1996-01-01

    The 'monazit' analytical program has been set up for routine work of Rare Earth Elements analysis in the monazite and xenotime minerals samples. Total relative error of the analysis is very low, less than 2.50%, and the reproducibility of counting statistic and stability of the instrument were very excellent. The precision and accuracy of the analytical program are very good with the maximum percentage relative are 5.22% and 1.61%, respectively. The mineral compositions of the 30 monazite samples have been also calculated using their chemical constituents, and the results were compared to the grain counting microscopic analysis

  10. Methods of Multivariate Analysis

    CERN Document Server

    Rencher, Alvin C

    2012-01-01

    Praise for the Second Edition "This book is a systematic, well-written, well-organized text on multivariate analysis packed with intuition and insight . . . There is much practical wisdom in this book that is hard to find elsewhere."-IIE Transactions Filled with new and timely content, Methods of Multivariate Analysis, Third Edition provides examples and exercises based on more than sixty real data sets from a wide variety of scientific fields. It takes a "methods" approach to the subject, placing an emphasis on how students and practitioners can employ multivariate analysis in real-life sit

  11. Factor analysis and scintigraphy

    International Nuclear Information System (INIS)

    Di Paola, R.; Penel, C.; Bazin, J.P.; Berche, C.

    1976-01-01

    The goal of factor analysis is usually to achieve reduction of a large set of data, extracting essential features without previous hypothesis. Due to the development of computerized systems, the use of largest sampling, the possibility of sequential data acquisition and the increase of dynamic studies, the problem of data compression can be encountered now in routine. Thus, results obtained for compression of scintigraphic images were first presented. Then possibilities given by factor analysis for scan processing were discussed. At last, use of this analysis for multidimensional studies and specially dynamic studies were considered for compression and processing [fr

  12. Applied nonstandard analysis

    CERN Document Server

    Davis, Martin

    2005-01-01

    Geared toward upper-level undergraduates and graduate students, this text explores the applications of nonstandard analysis without assuming any knowledge of mathematical logic. It develops the key techniques of nonstandard analysis at the outset from a single, powerful construction; then, beginning with a nonstandard construction of the real number system, it leads students through a nonstandard treatment of the basic topics of elementary real analysis, topological spaces, and Hilbert space.Important topics include nonstandard treatments of equicontinuity, nonmeasurable sets, and the existenc

  13. Basic stress analysis

    CERN Document Server

    Iremonger, M J

    1982-01-01

    BASIC Stress Analysis aims to help students to become proficient at BASIC programming by actually using it in an important engineering subject. It also enables the student to use computing as a means of learning stress analysis because writing a program is analogous to teaching-it is necessary to understand the subject matter. The book begins by introducing the BASIC approach and the concept of stress analysis at first- and second-year undergraduate level. Subsequent chapters contain a summary of relevant theory, worked examples containing computer programs, and a set of problems. Topics c

  14. Foundations of Risk Analysis

    CERN Document Server

    Aven, Terje

    2012-01-01

    Foundations of Risk Analysis presents the issues core to risk analysis - understanding what risk means, expressing risk, building risk models, addressing uncertainty, and applying probability models to real problems. The author provides the readers with the knowledge and basic thinking they require to successfully manage risk and uncertainty to support decision making. This updated edition reflects recent developments on risk and uncertainty concepts, representations and treatment. New material in Foundations of Risk Analysis includes:An up to date presentation of how to understand, define and

  15. Real Option Analysis (ROA

    Directory of Open Access Journals (Sweden)

    Armanto Witjaksono

    2003-03-01

    Full Text Available Net Present Value (NPV method have populer since middle 70’s and now most of expert felt that method has several limitation, especially if used to analyse big scale investment alocation capital. Another method that begin to popular is Real Option Analysis (ROA that use to replace Net Present Value (NPV method. The strenght of Real Option Analysis (ROA method is the flexiblelity in giving information for the decision maker. The weakness of Real Option Analysis (ROA method is the simple mathematic formula, as the formula in NPV method, is not found yet. 

  16. Fundamentals of mathematical analysis

    CERN Document Server

    Paul J Sally, Jr

    2013-01-01

    This is a textbook for a course in Honors Analysis (for freshman/sophomore undergraduates) or Real Analysis (for junior/senior undergraduates) or Analysis-I (beginning graduates). It is intended for students who completed a course in "AP Calculus", possibly followed by a routine course in multivariable calculus and a computational course in linear algebra. There are three features that distinguish this book from many other books of a similar nature and which are important for the use of this book as a text. The first, and most important, feature is the collection of exercises. These are spread

  17. Real analysis and probability

    CERN Document Server

    Ash, Robert B; Lukacs, E

    1972-01-01

    Real Analysis and Probability provides the background in real analysis needed for the study of probability. Topics covered range from measure and integration theory to functional analysis and basic concepts of probability. The interplay between measure theory and topology is also discussed, along with conditional probability and expectation, the central limit theorem, and strong laws of large numbers with respect to martingale theory.Comprised of eight chapters, this volume begins with an overview of the basic concepts of the theory of measure and integration, followed by a presentation of var

  18. Observations on risk analysis

    International Nuclear Information System (INIS)

    Thompson, W.A. Jr.

    1979-11-01

    This paper briefly describes WASH 1400 and the Lewis report. It attempts to define basic concepts such as risk and risk analysis, common mode failure, and rare event. Several probabilistic models which go beyond the WASH 1400 methodology are introduced; the common characteristic of these models is that they recognize explicitly that risk analysis is time dependent whereas WASH 1400 takes a per demand failure rate approach which obscures the important fact that accidents are time related. Further, the presentation of a realistic risk analysis should recognize that there are various risks which compete with one another for the lives of the individuals at risk. A way of doing this is suggested

  19. Bayesian nonparametric data analysis

    CERN Document Server

    Müller, Peter; Jara, Alejandro; Hanson, Tim

    2015-01-01

    This book reviews nonparametric Bayesian methods and models that have proven useful in the context of data analysis. Rather than providing an encyclopedic review of probability models, the book’s structure follows a data analysis perspective. As such, the chapters are organized by traditional data analysis problems. In selecting specific nonparametric models, simpler and more traditional models are favored over specialized ones. The discussed methods are illustrated with a wealth of examples, including applications ranging from stylized examples to case studies from recent literature. The book also includes an extensive discussion of computational methods and details on their implementation. R code for many examples is included in on-line software pages.

  20. Foundations of analysis

    CERN Document Server

    Taylor, Joseph L

    2012-01-01

    Foundations of Analysis is an excellent new text for undergraduate students in real analysis. More than other texts in the subject, it is clear, concise and to the point, without extra bells and whistles. It also has many good exercises that help illustrate the material. My students were very satisfied with it.-Nat Smale, University of Utah I have taught our Foundations of Analysis course (based on Joe Taylor.s book) several times recently, and have enjoyed doing so. The book is well-written, clear, and concise, and supplies the students with very good introductory discussions of the various t