Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 2 hours 1 min ago

Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases.

Thu, 02/07/2015 - 14:18
Effects of Olive Metabolites on DNA Cleavage Mediated by Human Type II Topoisomerases. Biochemistry. 2015 Jul 1; Authors: Vann KR, Sedgeman CA, Gopas J, Golan-Goldhirsh A, Osheroff N Abstract Several naturally occurring dietary polyphenols with chemopreventive or anticancer properties are topoisomerase II poisons. In order to identify additional phytochemicals that enhance topoisomerase II-mediated DNA cleavage, a library of 341 Mediterranean plant extracts was screened for activity against human topoisomerase IIα. An extract from Phillyrea latifolia L., a member of the olive tree family, displayed high activity against the human enzyme. Based on previous metabolomics studies, we identified several polyphenols (hydroxytyrosol, oleuropein, verbascoside, tyrosol, and caffeic acid) as potential candidates for topoisomerase II poisons. Of these, hydroxytyrosol, oleuropein, and verbascoside enhanced topoisomerase II-mediated DNA cleavage. The potency of these olive metabolites increased 10- to 100-fold in the presence of an oxidant. Hydroxytyrosol, oleuropein, and verbascoside displayed hallmark characteristics of covalent topoisomerase II poisons: 1) the activity of the metabolites was abrogated by a reducing agent, 2) compounds inhibited topoisomerase II activity when incubated with the enzyme prior to the addition of DNA, and 3) compounds were unable to poison a topoisomerase IIα construct that lacked the N-terminal domain. Because hydroxytyrosol, oleuropein, and verbascoside are broadly distributed across the olive family, extracts from the leaves, bark, and fruit of 11 olive tree species were tested for activity against human topoisomerase IIα. Several of the extracts enhanced enzyme-mediated DNA cleavage. Finally, a commercial olive leaf supplement and extra virgin olive oils pressed from a variety of Olea europea subspecies enhanced DNA cleavage mediated by topoisomerase IIα. Thus, olive metabolites appear to act as topoisomerase II poisons in complex formulations intended for human dietary consumption. PMID: 26132160 [PubMed - as supplied by publisher]

A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study.

Thu, 02/07/2015 - 14:18
Related Articles A statistical framework to model the meeting-in-the-middle principle using metabolomic data: application to hepatocellular carcinoma in the EPIC study. Mutagenesis. 2015 Jun 30; Authors: Assi N, Fages A, Vineis P, Chadeau-Hyam M, Stepien M, Duarte-Salles T, Byrnes G, Boumaza H, Knüppel S, Kühn T, Palli D, Bamia C, Boshuizen H, Bonet C, Overvad K, Johansson M, Travis R, Gunter MJ, Lund E, Dossus L, Elena-Herrmann B, Riboli E, Jenab M, Viallon V, Ferrari P Abstract Metabolomics is a potentially powerful tool for identification of biomarkers associated with lifestyle exposures and risk of various diseases. This is the rationale of the 'meeting-in-the-middle' concept, for which an analytical framework was developed in this study. In a nested case-control study on hepatocellular carcinoma (HCC) within the European Prospective Investigation into Cancer and nutrition (EPIC), serum (1)H nuclear magnetic resonance (NMR) spectra (800 MHz) were acquired for 114 cases and 222 matched controls. Through partial least square (PLS) analysis, 21 lifestyle variables (the 'predictors', including information on diet, anthropometry and clinical characteristics) were linked to a set of 285 metabolic variables (the 'responses'). The three resulting scores were related to HCC risk by means of conditional logistic regressions. The first PLS factor was not associated with HCC risk. The second PLS metabolomic factor was positively associated with tyrosine and glucose, and was related to a significantly increased HCC risk with OR = 1.11 (95% CI: 1.02, 1.22, P = 0.02) for a 1SD change in the responses score, and a similar association was found for the corresponding lifestyle component of the factor. The third PLS lifestyle factor was associated with lifetime alcohol consumption, hepatitis and smoking, and had negative loadings on vegetables intake. Its metabolomic counterpart displayed positive loadings on ethanol, glutamate and phenylalanine. These factors were positively and statistically significantly associated with HCC risk, with 1.37 (1.05, 1.79, P = 0.02) and 1.22 (1.04, 1.44, P = 0.01), respectively. Evidence of mediation was found in both the second and third PLS factors, where the metabolomic signals mediated the relation between the lifestyle component and HCC outcome. This study devised a way to bridge lifestyle variables to HCC risk through NMR metabolomics data. This implementation of the 'meeting-in-the-middle' approach finds natural applications in settings characterised by high-dimensional data, increasingly frequent in the omics generation. PMID: 26130468 [PubMed - as supplied by publisher]

Distinct metabolomic profiles of papillary thyroid carcinoma and benign thyroid adenoma.

Thu, 02/07/2015 - 14:18
Related Articles Distinct metabolomic profiles of papillary thyroid carcinoma and benign thyroid adenoma. J Proteome Res. 2015 Jul 1; Authors: Xu Y, Zheng X, Qiu Y, Jia W, Wang J, Yin S Abstract Papillary thyroid carcinoma (PTC) and benign thyroid adenoma (BTA) are the most common head and neck tumors. However, the metabolic differences between PTC and BTA have not been characterized. The aim of this study was to identify the metabolic profiles of these two types of tumors using a metabolomics approach. Tumors and adjacent non-tumor specimens collected from 57 patients with PTC and 48 patients with BTA were profiled using gas chromatography-time-of-flight mass spectrometry and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. A panel of 46 and 44 differentially expressed metabolites were identified in the PTC and BTA specimens, respetively, and compared with non-tumor tissues. Common metabolic signatures, as characterized by increased glycolysis, amino acid metabolism, one carbon metabolism and tryptophan metabolism, were found in both types of tumors. Purine and pyrimidine metabolism was significantly elevated in the PTC specimens, and taurine and hypotaurine levels were also higher in the PTC tissues. Increased fatty acid and bile acid levels were found, especially in the BTA tissues. The metabolic profiles of the PTC and BTA tissues include both similar and remarkably different metabolites, suggesting the presence of common and unique mechanistic pathways in these types of tumors during tumorigenesis. PMID: 26130307 [PubMed - as supplied by publisher]

Metabolic Responses in Candida tropicalis to Complex Inhibitors During Xylitol Bioconversion.

Thu, 02/07/2015 - 14:18
Related Articles Metabolic Responses in Candida tropicalis to Complex Inhibitors During Xylitol Bioconversion. Fungal Genet Biol. 2015 Jun 27; Authors: Wang S, Li H, Fan X, Zhang J, Tang P, Yuan Q Abstract During xylitol fermentation, Candida tropicalis is often inhibited by inhibitors in hemicellulose hydrolysate. The mechanisms involved in the metabolic responses to inhibitor stress and the resistances to inhibitors are still not clear. To understand the inhibition mechanisms and the metabolic responses to inhibitors, a GC/MS-based metabolomics approach was performed on C. tropicalis treated with and without complex inhibitors (CI, including furfural, phenol and acetic acid). Partial least squares discriminant analysis was used to determine the metabolic variability between CI-treated groups and control groups, and 25 metabolites were identified as possible entities responsible for the discrimination caused by inhibitors. We found that xylose uptake rate and xylitol oxidation rate were promoted by CI treatment. Metabolomics analysis showed that the flux from xylulose to pentose phosphate pathway increased, and tricarboxylic acid cycle was disturbed by CI. Moreover, the changes in levels of 1, 3-propanediol, trehalose, saturated fatty acids and amino acids showed different mechanisms involved in metabolic responses to inhibitor stress. The increase of 1, 3-propanediol was considered to be correlated with regulating redox balance and osmoregulation. The increase of trehalose might play a role in protein stabilization and cellular membranes protection. Saturated fatty acids could cause the decrease of membrane fluidity and make the plasma membrane rigid to maintain the integrity of plasma membrane. The deeper understanding of the inhibition mechanisms and the metabolic responses to inhibitors will provide us with more information on the metabolism regulation during xylitol bioconversion and the construction of industrial strains with inhibitor tolerance for better utilization of bioresource. PMID: 26127015 [PubMed - as supplied by publisher]

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

Thu, 02/07/2015 - 14:18
Related Articles Metabolic study of enrofloxacin and metabolic profile modifications in broiler chicken tissues after drug administration. Food Chem. 2015 Apr 1;172:30-9 Authors: Morales-Gutiérrez FJ, Barbosa J, Barrón D Abstract In this work, the identification and distribution of the metabolites from enrofloxacin (ENR) in liver, kidney and muscle tissues from broiler chickens subjected to a pharmacological treatment was studied. In addition, qualitative analyses of changes in the metabolic profile in those tissues after drug administration were also investigated. As a result, a total of 31 different metabolites from ENR were identified, which ciprofloxacin (CIP) and desethylene-ENR were the major metabolites. After four days of withdrawal period, most of the metabolites were excreted, but residues of ENR and CIP still persisted in tissues at a concentration under the permitted maximum residue limit (MRL). Non-medicated, medicated and post-treatment samples of chicken tissues were clearly clustered according to their metabolite profile by principal component analysis and partial least squares discriminant analysis, which indicates that endogenous metabolites have not returned to their original levels after the withdrawal period. A total of 22 relevant mass features contributing to this separation as potential markers of chicken samples were tentatively identified. PMID: 25442520 [PubMed - indexed for MEDLINE]

Lipidomics applications for discovering biomarkers of diseases in clinical chemistry.

Thu, 02/07/2015 - 14:18
Related Articles Lipidomics applications for discovering biomarkers of diseases in clinical chemistry. Int Rev Cell Mol Biol. 2014;313:1-26 Authors: Zhao YY, Cheng XL, Lin RC Abstract Lipids are the fundamental components of biological membranes as well as the metabolites of organisms. Lipids play diverse and important roles in biologicals. The lipid imbalance is closely associated with numerous human lifestyle-related diseases, such as atherosclerosis, obesity, diabetes, and Alzheimer's disease. Lipidomics or lipid profiling is a system-based study of all lipids aiming at comprehensive analysis of lipids in the biological system. Lipidomics has been accepted as a lipid-related research tool in lipid biochemistry, clinical biomarker discovery, disease diagnosis, and in understanding disease pathology. Lipidomics will not only provide insights into the specific functions of lipid species in health and disease, but will also identify potential biomarkers for establishing preventive or therapeutic programs for human diseases. This review presents an overview of lipidomics followed by in-depth discussion of its application to the study of human diseases, including extraction methods of lipids, analytical technologies, data analysis, and clinical research in cancer, neuropsychiatric disease, cardiovascular disease, kidney disease, and respiratory disease. We describe the current status of the identification of metabolic biomarkers in different diseases. We also discuss the lipidomics for the future perspectives and their potential problems. The application of lipidomics in clinical studies may provide new insights into lipid profiling and pathophysiological mechanisms. PMID: 25376488 [PubMed - indexed for MEDLINE]

Disposition and metabolic profiling of [(14)C]cerlapirdine using accelerator mass spectrometry.

Thu, 02/07/2015 - 14:18
Related Articles Disposition and metabolic profiling of [(14)C]cerlapirdine using accelerator mass spectrometry. Drug Metab Dispos. 2014 Dec;42(12):2023-32 Authors: Tse S, Leung L, Raje S, Seymour M, Shishikura Y, Obach RS Abstract Cerlapirdine (SAM-531, PF-05212365) is a selective, potent, full antagonist of the 5-hydroxytryptamine 6 (5-HT6) receptor. Cerlapirdine and other 5-HT6 receptor antagonists have been in clinical development for the symptomatic treatment of Alzheimer's disease. A human absorption, distribution, metabolism, and excretion study was conducted to gain further understanding of the metabolism and disposition of cerlapirdine. Because of the low amount of radioactivity administered, total (14)C content and metabolic profiles in plasma, urine, and feces were determined using accelerator mass spectrometry (AMS). After a single, oral 5-mg dose of [(14)C]cerlapirdine (177 nCi), recovery of total (14)C was almost complete, with feces being the major route of elimination of the administered dose, whereas urinary excretion played a lesser role. The extent of absorption was estimated to be at least 70%. Metabolite profiling in pooled plasma samples showed that unchanged cerlapirdine was the major drug-related component in circulation, representing 51% of total (14)C exposure in plasma. One metabolite (M1, desmethylcerlapirdine) was detected in plasma, and represented 9% of the total (14)C exposure. In vitro cytochrome P450 reaction phenotyping studies showed that M1 was formed primarily by CYP2C8 and CYP3A4. In pooled urine samples, three major drug-related peaks were detected, corresponding to cerlapirdine-N-oxide (M3), cerlapirdine, and desmethylcerlapirdine. In feces, cerlapirdine was the major (14)C component excreted, followed by desmethylcerlapirdine. The results of this study demonstrate that the use of the AMS technique enables comprehensive quantitative elucidation of the disposition and metabolic profiles of compounds administered at a low radioactive dose. PMID: 25217486 [PubMed - indexed for MEDLINE]

MetabNet: An R Package for Metabolic Association Analysis of High-Resolution Metabolomics Data.

Wed, 01/07/2015 - 13:16
Related Articles MetabNet: An R Package for Metabolic Association Analysis of High-Resolution Metabolomics Data. Front Bioeng Biotechnol. 2015;3:87 Authors: Uppal K, Soltow QA, Promislow DE, Wachtman LM, Quyyumi AA, Jones DP Abstract Liquid-chromatography high-resolution mass spectrometry provides capability to measure >40,000 ions derived from metabolites in biologic samples. This presents challenges to confirm identities of known chemicals and delineate potential metabolic pathway associations of unidentified chemicals. We provide an R package for metabolic network analysis, MetabNet, to perform targeted metabolome-wide association study of specific metabolites to facilitate detection of their related metabolic pathways and network structures. PMID: 26125020 [PubMed]

Chronic inflammation: is it the driver or is it paving the road for malignant transformation?

Wed, 01/07/2015 - 13:16
Related Articles Chronic inflammation: is it the driver or is it paving the road for malignant transformation? Genes Cancer. 2015 May;6(5-6):214-9 Authors: Afrasiabi K, Zhou YH, Fleischman A Abstract Chronic inflammation in well-defined mouse models such as Giα2 knock out mouse has been shown to trigger formation and expansion of hypoxic niches and also leads to up regulation of NFĸB, offering cells which have adapted their genetic machinery to hypoxia a unique survival advantage. These adapted cells have been shown to acquire stem cell-like capabilities as shown by up regulation of stem cell markers. Such long lived cells become permanent residents in sub mucosa and acquire a malignant phenotype from long-term exposure to noxious environmental agents due to a barrier defect secondary to down regulation of barrier proteins such as Zo1 and Occludin. Indeed mitotic spindle disorientation in such mice has been proposed as another contributory factor to malignant transformation. Sterilization of bowel lumen of these mice through different techniques has prevented malignant transformation in the presence of chronic inflammation. These facts stand strongly against chronic inflammation as a true driver of carcinogenesis but clearly support its role in facilitating the emergence of the neoplastic clone. PMID: 26124920 [PubMed]

The therapy of gefitinib towards breast cancer partially through reversing breast cancer biomarker arginine.

Wed, 01/07/2015 - 13:16
Related Articles The therapy of gefitinib towards breast cancer partially through reversing breast cancer biomarker arginine. Afr Health Sci. 2015 Jun;15(2):594-7 Authors: Geng D, Sun D, Zhang L, Zhang W Abstract BACKGROUND: Breast cancer remains the leading reason of cancer death among women worldwide, and gefitinib is the efficient drug for breast cancer. AIMS: To use targeted metabolomics method to elucidate the therapeutic mechanism of gefitinib through profiling the amino acids. METHODS: Healthy women (n=56) and women with breast cancer (n=60) were enrolled in Affiliated Yuhuangding hospital, medical college of Qingdao University from 2012-2014. API 3200 triple quadrupole mass spectrometer was used to analyze the serum samples. RESULTS: The concentration of amino acids was compared between healthy women and women with breast cancers. Compared with the healthy women, the concentration of arginine in breast cancer women significantly decreased (p<0.0001). To show the representative capability of arginine towards the pathogenesis of breast cancers, the receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to be 0.96 ± 0.02, indicating the high predictive capability of arginine for breast cancer . The reversing ability of gefitinib towards the level of arginine was further determined, and 1 month treatment of gefitinib (500 mg/day) significantly reversed the arginine level of breast cancer patients (p<0.0001). CONCLUSION: The therapy of gefitinib towards breast cancer through reversing breast cancer biomarker arginine was demonstrated. PMID: 26124808 [PubMed - in process]

Educating future nursing scientists: Recommendations for integrating omics content in PhD programs.

Wed, 01/07/2015 - 13:16
Related Articles Educating future nursing scientists: Recommendations for integrating omics content in PhD programs. Nurs Outlook. 2015 Jun 12; Authors: Conley YP, Heitkemper M, McCarthy D, Anderson CM, Corwin EJ, Daack-Hirsch S, Dorsey SG, Gregory KE, Groer MW, Henly SJ, Landers T, Lyon DE, Taylor JY, Voss J Abstract Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Science's Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals. PMID: 26123776 [PubMed - as supplied by publisher]

Computational analysis and ratiometric comparison approaches aimed to assist column selection in hydrophilic interaction liquid chromatography-tandem mass spectrometry targeted metabolomics.

Wed, 01/07/2015 - 13:16
Related Articles Computational analysis and ratiometric comparison approaches aimed to assist column selection in hydrophilic interaction liquid chromatography-tandem mass spectrometry targeted metabolomics. J Chromatogr A. 2015 Jun 14; Authors: Sampsonidis I, Witting M, Koch W, Virgiliou C, Gika HG, Schmitt-Kopplin P, Theodoridis GA Abstract In the present work two different approaches, a semi-quantitative and a Derringer function approach, were developed to assist column selection for method development in targeted metabolomics. These approaches were applied in the performance assessment of three HILIC columns with different chemistries (an amide, a diol and a zwitterionic phase). This was the first step for the development of a HILIC UPLC-MS/MS method that should be capable to analyze a large number of polar metabolites. Two gradient elution profiles and two mobile phase pH values were tested for the analysis of multi-analyte mixtures. Acquired chromatographic data were firstly treated by a ratiometric, "semi-quantitative" approach which quantifies various overall analysis parameters (e.g. the percent of detected compounds, retentivity and resolved critical pairs). These parameters were used to assess chromatographic performance in a rather conventional/traditional and cumbersome/labor-intensive way. Secondly, a comprehensive and automated comparison of the three columns was performed by monitoring several well-known chromatographic parameters (peak width, resolution, tailing factor, etc.) using a lab-built programming script which calculates overall desirability utilizing Derringer functions. Derringer functions exhibit the advantage that column performance is ultimately expressed in an objective single and quantitative value which can be easily interpreted. In summary, results show that each column exhibits unique strengths in metabolic profiling of polar compounds. The applied methodology proved useful for the selection of the most effective chromatographic system during method development for LC-MS/MS targeted metabolomics, while it could further assist in the selection of chromatographic conditions for the development of multi-analyte methods. PMID: 26122858 [PubMed - as supplied by publisher]

Isoprene emission by poplar is not important for the feeding behaviour of poplar leaf beetles.

Wed, 01/07/2015 - 13:16
Related Articles Isoprene emission by poplar is not important for the feeding behaviour of poplar leaf beetles. BMC Plant Biol. 2015;15:165 Authors: Müller A, Kaling M, Faubert P, Gort G, Smid HM, Van Loon JJ, Dicke M, Kanawati B, Schmitt-Kopplin P, Polle A, Schnitzler JP, Rosenkranz M Abstract BACKGROUND: Chrysomela populi (poplar leaf beetle) is a common herbivore in poplar plantations whose infestation causes major economic losses. Because plant volatiles act as infochemicals, we tested whether isoprene, the main volatile organic compound (VOC) produced by poplars (Populus x canescens), affects the performance of C. populi employing isoprene emitting (IE) and transgenic isoprene non-emitting (NE) plants. Our hypothesis was that isoprene is sensed and affects beetle orientation or that the lack of isoprene affects plant VOC profiles and metabolome with consequences for C. populi feeding. RESULTS: Electroantennographic analysis revealed that C. populi can detect higher terpenes, but not isoprene. In accordance to the inability to detect isoprene, C. populi showed no clear preference for IE or NE poplar genotypes in the choice experiments, however, the beetles consumed a little bit less leaf mass and laid fewer eggs on NE poplar trees in field experiments. Slight differences in the profiles of volatile terpenoids between IE and NE genotypes were detected by gas chromatography - mass spectrometry. Non-targeted metabolomics analysis by Fourier Transform Ion Cyclotron Resonance Mass Spectrometer revealed genotype-, time- and herbivore feeding-dependent metabolic changes both in the infested and adjacent undamaged leaves under field conditions. CONCLUSIONS: We show for the first time that C. populi is unable to sense isoprene. The detected minor differences in insect feeding in choice experiments and field bioassays may be related to the revealed changes in leaf volatile emission and metabolite composition between the IE and NE poplars. Overall our results indicate that lacking isoprene emission is of minor importance for C. populi herbivory under natural conditions, and that the lack of isoprene is not expected to change the economic losses in poplar plantations caused by C. populi infestation. PMID: 26122266 [PubMed - in process]

The current epidemiology and clinical decisions surrounding acute respiratory infections.

Wed, 01/07/2015 - 13:16
Related Articles The current epidemiology and clinical decisions surrounding acute respiratory infections. Trends Mol Med. 2014 Oct;20(10):579-88 Authors: Zaas AK, Garner BH, Tsalik EL, Burke T, Woods CW, Ginsburg GS Abstract Acute respiratory infection (ARI) is a common diagnosis in outpatient and emergent care settings. Currently available diagnostics are limited, creating uncertainty in the use of antibacterial, antiviral, or supportive care. Up to 72% of ambulatory care patients with ARI are treated with an antibacterial, despite only a small fraction actually needing one. Antibiotic overuse is not restricted to ambulatory care: ARI accounts for approximately 5 million emergency department (ED) visits annually in the USA, where 52-61% of such patients receive antibiotics. Thus, an accurate test for the presence or absence of viral or bacterial infection is needed. In this review, we focus on recent research showing that the host-response (genomic, proteomic, or miRNA) can accomplish this task. PMID: 25201713 [PubMed - indexed for MEDLINE]

Evaluation of volatile metabolites as markers in Lycopersicon esculentum L. cultivars discrimination by multivariate analysis of headspace solid phase microextraction and mass spectrometry data.

Wed, 01/07/2015 - 13:16
Related Articles Evaluation of volatile metabolites as markers in Lycopersicon esculentum L. cultivars discrimination by multivariate analysis of headspace solid phase microextraction and mass spectrometry data. Food Chem. 2014 Feb 15;145:653-63 Authors: Figueira J, Câmara H, Pereira J, Câmara JS Abstract To gain insights on the effects of cultivar on the volatile metabolomic expression of different tomato (Lycopersicon esculentum L.) cultivars--Plum, Campari, Grape, Cherry and Regional, cultivated under similar edafoclimatic conditions, and to identify the most discriminate volatile marker metabolites related to the cultivar, the chromatographic profiles resulting from headspace solid phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-qMS) analysis, combined with multivariate analysis were investigated. The data set composed by the 77 volatile metabolites identified in the target tomato cultivars, 5 of which (2,2,6-trimethylcyclohexanone, 2-methyl-6-methyleneoctan-2-ol, 4-octadecyl-morpholine, (Z)-methyl-3-hexenoate and 3-octanone) are reported for the first time in tomato volatile metabolomic composition, was evaluated by chemometrics. Firstly, principal component analysis was carried out in order to visualise data trends and clusters, and then, linear discriminant analysis in order to detect the set of volatile metabolites able to differentiate groups according to tomato cultivars. The results obtained revealed a perfect discrimination between the different Lycopersicon esculentum L. cultivars considered. The assignment success rate was 100% in classification and 80% in prediction ability by using "leave-one-out" cross-validation procedure. The volatile profile was able to differentiate all five cultivars and revealed complex interactions between them including the participation in the same biosynthetic pathway. The volatile metabolomic platform for tomato samples obtained by HS-SPME/GC-qMS here described, and the interrelationship detected among the volatile metabolites can be used as a roadmap for biotechnological applications, namely to improve tomato aroma and their acceptance in the final consumer, and for traceability studies. PMID: 24128528 [PubMed - indexed for MEDLINE]

Looking into living cell systems: Planar waveguide microfluidic NMR detector for in vitro metabolomics of tumor spheroids.

Tue, 30/06/2015 - 12:10
Looking into living cell systems: Planar waveguide microfluidic NMR detector for in vitro metabolomics of tumor spheroids. Anal Chem. 2015 Jun 29; Authors: Kalfe A, Telfah A, Lambert J, Hergenroeder R Abstract The complex cell metabolism and its link to oncogenic signaling pathways have received huge interest within the last years. But the lack of advanced analytical tools for the investigation of living cell metabolism is still a challenge to be faced. Therefore, we designed and fabricated a novel miniaturized microslot NMR detector with on-board heater integrated with a microfluidic device as NMR sample holder. For the first time, a tumor spheroid of 500 µm diameter and consisting of 9000 cells has been studied non-invasively and online for 24 hours. The dynamic process of production and degradation of 23 intra- and extracellular metabolites were monitored. Remarkably high concentrations of lactate and alanine were observed being an indicator for a shift from oxidative to glycolytic metabolism. In summary, this methodical development has proven to be a successful analytical tool for the elucidation of cellular functions and their corresponding biochemical pathways. Additionally, the planar geometry of the microslot NMR detector allows the hyphenation with versatile lab-on-a chip (LOC) technology. This opens a new window for metabolomics studies on living cells and can be implemented into new application fields in biotechnology and life sciences. PMID: 26121119 [PubMed - as supplied by publisher]

New insights and biomarkers for Type 1 Diabetes: Review for Scandinavian Journal of Immunology.

Tue, 30/06/2015 - 12:10
Related Articles New insights and biomarkers for Type 1 Diabetes: Review for Scandinavian Journal of Immunology. Scand J Immunol. 2015 Jun 28; Authors: Heinonen MT, Moulder R, Lahesmaa R Abstract The increasing incidence of type 1 diabetes observed in the past 60 years has spawned massive efforts in multiple research fields to elucidate the etiology of this disease. While GWAS studies provide a good genetic basis for the current knowledge, it is clear that environmental triggers and their influence in disease prevalence and origin are is highly important. The realization of disease heterogeneity has created a requirement for better biomarkers to complement the known autoantibody markers and to more successfully predict the severity and onset time of the disease. Such biomarkers would be needed both for prevention as well as for monitoring disease activity and response to preventive and therapeutic measures. Systematic holistic approaches concentrating on the triggering molecular mechanisms, pancreatic beta cells, immune response as well as the influence of diet and environment are necessary to understand the disease pathogenesis and find a cure. The current genomic knowledge is being broadened with accompanying studies in epigenetics and transcriptomic regulation, metabolomics, proteomics and lipidomics, covering the whole system from beta cells, the profile and cellular balance of the infiltrating lymphocytes to gut microbiota and viral infections. Here we highlight interesting recent findings in type 1 diabetes research. This article is protected by copyright. All rights reserved. PMID: 26119046 [PubMed - as supplied by publisher]

Metabolome progression during early gut microbial colonization of gnotobiotic mice.

Tue, 30/06/2015 - 12:10
Related Articles Metabolome progression during early gut microbial colonization of gnotobiotic mice. Sci Rep. 2015;5:11589 Authors: Marcobal A, Yusufaly T, Higginbottom S, Snyder M, Sonnenburg JL, Mias GI Abstract The microbiome has been implicated directly in host health, especially host metabolic processes and development of immune responses. These are particularly important in infants where the gut first begins being colonized, and such processes may be modeled in mice. In this investigation we follow longitudinally the urine metabolome of ex-germ-free mice, which are colonized with two bacterial species, Bacteroides thetaiotaomicron and Bifidobacterium longum. High-throughput mass spectrometry profiling of urine samples revealed dynamic changes in the metabolome makeup, associated with the gut bacterial colonization, enabled by our adaptation of non-linear time-series analysis to urine metabolomics data. Results demonstrate both gradual and punctuated changes in metabolite production and that early colonization events profoundly impact the nature of small molecules circulating in the host. The identified small molecules are implicated in amino acid and carbohydrate metabolic processes, and offer insights into the dynamic changes occurring during the colonization process, using high-throughput longitudinal methodology. PMID: 26118551 [PubMed - in process]

[UPLC/Q-TOF MS and NMR plant metabolomics approach in studying the effect of growth year on the quality of Polygala tenuifolia].

Tue, 30/06/2015 - 12:10
Related Articles [UPLC/Q-TOF MS and NMR plant metabolomics approach in studying the effect of growth year on the quality of Polygala tenuifolia]. Yao Xue Xue Bao. 2015 Mar;50(3):340-7 Authors: Xue Y, Li XW, Li ZY, Zeng ZP, Zhang FS, Li AP, Qin XM, Peng B Abstract Growth year is one of the important factors for the quality of Polygala tenufolia. In this study, primary metabolites and secondary metabolites were compared in 1, 2 and 3 years old P. tenufolia cultivated in Shaanxi Heyang. The samples were subjected to ultra-high performance liquid chromatography (UPLC)-quadrupole time-of-flight mass spectrometry (Q-TOF MS) and nuclear magnetic resonance (NMR) analysis, and the obtained data were analyzed using principal component analysis (PCA) and other statistical analysis methods. In addition, content and correlation of different metabolites were also calculated. The results showed no significance between main component contents in 2 year-old and 3 year-old P. Tenufolia, but 1 year-old was statistically different. The contents of primary metabolites, such as fructose, sucrose, and choline increased as time goes on, while glycine and raffinose decreased. The contents of secondary metabolites, such as onjisaponin Fg, polygalasaponin XXVIII, polygalasaponin XXXII increased, while polygalaxanthone III and parts of oligosaccharide multi-ester including tenuifoliose A, tenuifoliose C, tenuifoliose C2 and tenuifoliose H decreased with the extension of the growth years. Growth years has important impact on the quality of P. tenuifolia and the existing growing years of commodity P. tenuifolia have its scientific evidence. This study supplied a new method for the quality evaluation of Chinese medicinal materials. PMID: 26118115 [PubMed - in process]

Evaluation of comprehensive two-dimensional gas chromatography with accurate mass time-of-flight mass spectrometry for the metabolic profiling of plant-fungus interaction in Aquilaria malaccensis.

Tue, 30/06/2015 - 12:10
Related Articles Evaluation of comprehensive two-dimensional gas chromatography with accurate mass time-of-flight mass spectrometry for the metabolic profiling of plant-fungus interaction in Aquilaria malaccensis. J Chromatogr A. 2015 Mar 27;1387:104-15 Authors: Wong YF, Chin ST, Perlmutter P, Marriott PJ Abstract To explore the possible obligate interactions between the phytopathogenic fungus and Aquilaria malaccensis which result in generation of a complex array of secondary metabolites, we describe a comprehensive two-dimensional gas chromatography (GC × GC) method, coupled to accurate mass time-of-flight mass spectrometry (TOFMS) for the untargeted and comprehensive metabolic profiling of essential oils from naturally infected A. malaccensis trees. A polar/non-polar column configuration was employed, offering an improved separation pattern of components when compared to other column sets. Four different grades of the oils displayed quite different metabolic patterns, suggesting the evolution of a signalling relationship between the host tree (emergence of various phytoalexins) and fungi (activation of biotransformation). In total, ca. 550 peaks/metabolites were detected, of which tentative identification of 155 of these compounds was reported, representing between 20.1% and 53.0% of the total ion count. These are distributed over the chemical families of monoterpenic and sesquiterpenic hydrocarbons, oxygenated monoterpenes and sesquiterpenes (comprised of ketone, aldehyde, oxide, alcohol, lactone, keto-alcohol and diol), norterpenoids, diterpenoids, short chain glycols, carboxylic acids and others. The large number of metabolites detected, combined with the ease with which they are located in the 2D separation space, emphasises the importance of a comprehensive analytical approach for the phytochemical analysis of plant metabolomes. Furthermore, the potential of this methodology in grading agarwood oils by comparing the obtained metabolic profiles (pattern recognition for unique metabolite chemical families) is discussed. The phytocomplexity of the agarwood oils signified the production of a multitude of plant-fungus mediated secondary metabolites as chemical signals for natural ecological communication. To the best of our knowledge, this is the most complete information available so far about essential oils of A. malaccensis, which represents a valuable extension to available data for advanced studies on microbial-mediated biotransformation of terpenes, and offers promise for potential discovery of unanticipated phytochemicals, and biotechnological exploitation. PMID: 25704770 [PubMed - indexed for MEDLINE]

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