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: 1 hour 21 min ago

LC-MS based metabolomics identification of novel biomarkers of tobacco smoke induced chronic bronchitis.

Tue, 22/09/2015 - 13:29
LC-MS based metabolomics identification of novel biomarkers of tobacco smoke induced chronic bronchitis. Biomed Chromatogr. 2015 Sep 21; Authors: Ren X, Zhang J, Fu X, Ma S, Wang C, Wang J, Tian S, Liu S, Zhao B, Wang X Abstract Tobacco smoke (TS) is a major causative agent to lead to chronic bronchitis (CB). However the mechanisms of CB induced by TS are unclear. In this report, rats were exposed to different concentrations of TS and the metabolic features of CB were characterized by using a non-targeted metabolic profiling method based on liquid chromatography-mass spectrometry (LC-MS) to detect the altered metabolic patterns in serum from CB rats and investigate the mechanisms of CB. 11 potential biomarkers were identified in serum of rats. Among them, the levels of lysophosphatidylethanolamine (18:1), lysophosphatidic acid (18:1), lysophosphatidylethanolamine (18:0), lysophosphatidylethanolamine (16:0), lysophosphatidylethanolamine (20:4), docosahexaenoic acid, 5-hydroxyindoleacetic acid and 5'-carboxy-γ-tocopherol were higher in TS group compared to control group. Conversely, the levels of 4-imidazolone-5-propionic acid, 12-hydroxyeicosatetraenoic acid and uridine were lower in TS group. The results indicated that the mechanism of CB was related to amino acid metabolism and lipid metabolism, particularly lipid metabolism. In addition, lysophosphatidylethanolamines were proved to be important mediators, which could be used as biomarkers to diagnose CB. These results also suggested that metabolomics was suitable for diagnosing CB and elucidating the possible metabolic pathways of TS-induced CB. This article is protected by copyright. All rights reserved. PMID: 26390017 [PubMed - as supplied by publisher]

Metabolomic Screening of Tumor Tissue and Serum in Glioma Patients Reveals Diagnostic and Prognostic Information.

Tue, 22/09/2015 - 13:29
Metabolomic Screening of Tumor Tissue and Serum in Glioma Patients Reveals Diagnostic and Prognostic Information. Metabolites. 2015;5(3):502-520 Authors: Mörén L, Bergenheim AT, Ghasimi S, Brännström T, Johansson M, Antti H Abstract Glioma grading and classification, today based on histological features, is not always easy to interpret and diagnosis partly relies on the personal experience of the neuropathologists. The most important feature of the classification is the aimed correlation between tumor grade and prognosis. However, in the clinical reality, large variations exist in the survival of patients concerning both glioblastomas and low-grade gliomas. Thus, there is a need for biomarkers for a more reliable classification of glioma tumors as well as for prognosis. We analyzed relative metabolite concentrations in serum samples from 96 fasting glioma patients and 81 corresponding tumor samples with different diagnosis (glioblastoma, oligodendroglioma) and grade (World Health Organization (WHO) grade II, III and IV) using gas chromatography-time of flight mass spectrometry (GC-TOFMS). The acquired data was analyzed and evaluated by pattern recognition based on chemometric bioinformatics tools. We detected feature patterns in the metabolomics data in both tumor and serum that distinguished glioblastomas from oligodendrogliomas (p(tumor) = 2.46 × 10(-8), p(serum) = 1.3 × 10(-5)) and oligodendroglioma grade II from oligodendroglioma grade III (p(tumor) = 0.01, p(serum) = 0.0008). Interestingly, we also found patterns in both tumor and serum with individual metabolite features that were both elevated and decreased in patients that lived long after being diagnosed with glioblastoma compared to those who died shortly after diagnosis (p(tum)(o)(r) = 0.006, p(serum) = 0.004; AUROCC(tumor) = 0.846 (0.647-1.000), AUROCC(serum) = 0.958 (0.870-1.000)). Metabolic patterns could also distinguish long and short survival in patients diagnosed with oligodendroglioma (p(tumor) = 0.01, p(serum) = 0.001; AUROCC(tumor) = 1 (1.000-1.000), AUROCC(serum) = 1 (1.000-1.000)). In summary, we found different metabolic feature patterns in tumor tissue and serum for glioma diagnosis, grade and survival, which indicates that, following further verification, metabolomic profiling of glioma tissue as well as serum may be a valuable tool in the search for latent biomarkers for future characterization of malignant glioma. PMID: 26389964 [PubMed - as supplied by publisher]

GC-TOF-MS-based serum metabolomic investigations of naked oat bran supplementation in high-fat-diet-induced dyslipidemic rats.

Tue, 22/09/2015 - 13:29
GC-TOF-MS-based serum metabolomic investigations of naked oat bran supplementation in high-fat-diet-induced dyslipidemic rats. J Nutr Biochem. 2015 Aug 8; Authors: Gu J, Jing L, Ma X, Zhang Z, Guo Q, Li Y Abstract The present study aimed to explore the metabolic response of oat bran consumption in dyslipidemic rats by a high-throughput metabolomics approach. Four groups of Sprague-Dawley rats were used: N group (normal chow diet), M group (dyslipidemia induced by 4-week high-fat feeding, then normal chow diet), OL group and OH group (dyslipidemia induced, then normal chow diet supplemented with 10.8% or 43.4% naked oat bran). Intervention lasted for 12weeks. Gas chromatography quadrupole time-of-flight mass spectrometry was used to identify serum metabolite profiles. Results confirmed the effects of oat bran on improving lipidemic variables and showed distinct metabolomic profiles associated with diet intervention. A number of endogenous molecules were changed by high-fat diet and normalized following supplementation of naked oat bran. Elevated levels of serum unsaturated fatty acids including arachidonic acid (Log2Fold of change=0.70, P=.02 OH vs. M group), palmitoleic acid (Log2Fold of change=1.24, P=.02 OH vs. M group) and oleic acid (Log2Fold of change=0.66, P=.04 OH vs. M group) were detected after oat bran consumption. Furthermore, consumption of oat bran was also characterized by higher levels of methionine and S-adenosylmethionine. Pathway exploration found that most of the discriminant metabolites were involved in fatty acid biosynthesis, biosynthesis and metabolism of amino acids, microbial metabolism in diverse environments and biosynthesis of plant secondary metabolites. These results point to potential biomarkers and underlying benefit of naked oat bran in the context of diet-induced dyslipidemia and offer some insights into the mechanism exploration. PMID: 26388495 [PubMed - as supplied by publisher]

Development of high throughput 96-blade solid phase microextraction-liquid chromatrography-mass spectrometry protocol for metabolomics.

Tue, 22/09/2015 - 13:29
Development of high throughput 96-blade solid phase microextraction-liquid chromatrography-mass spectrometry protocol for metabolomics. Anal Chim Acta. 2015 Sep 10;892:95-104 Authors: Mousavi F, Bojko B, Pawliszyn J Abstract In metabolomics, the workflow for quantitative and comprehensive metabolic mapping of cellular metabolites can be a very challenging undertaking. Sampling and sample preparation play a significant role in untargeted analysis, as they may affect the composition of the analyzed metabolome. In the current work, different solid phase microextraction (SPME) coating chemistries were developed and applied to provide simultaneous extraction of a wide range of both hydrophobic and hydrophilic cellular metabolites produced by a model organism, Escherichia coli. Three different LC-MS methods were also evaluated for analysis of extracted metabolites. Finally, over 200 cellular metabolites were separated and detected with widely varying hydrophobicities ranging within -7 < log P < 15, including amino acids, peptides, nucleotides, carbohydrates, polycarboxylic acids, vitamins, phosphorylated compounds, and lipids such as hydrophobic phospholipids, prenol lipids, and fatty acids at the stationary phase of the E. coli life cycle using the developed 96-blade SPME-LC-MS method. PMID: 26388479 [PubMed - in process]

Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation.

Tue, 22/09/2015 - 13:29
Metabolomic profiling of the heart during acute ischemic preconditioning reveals a role for SIRT1 in rapid cardioprotective metabolic adaptation. J Mol Cell Cardiol. 2015 Sep 17; Authors: Nadtochiy SM, Urciuoli W, Zhang J, Schafer X, Munger J, Brookes PS Abstract Ischemic preconditioning (IPC) protects tissues such as the heart from prolonged ischemia-reperfusion (IR) injury. We previously showed that the lysine deacetylase SIRT1 is required for acute IPC, and has numerous metabolic targets. While it is known that metabolism is altered during IPC, the underlying metabolic regulatory mechanisms are unknown, including the relative importance of SIRT1. Thus, we sought to test the hypothesis that some of the metabolic adaptations that occur in IPC may require SIRT1 as a regulatory mediator. Using both ex-vivo-perfused and in-vivo mouse hearts, LC-MS/MS based metabolomics and (13)C-labeled substrate tracing, we found that acute IPC altered several metabolic pathways including: (i) stimulation of glycolysis, (ii) increased synthesis of glycogen and several amino acids, (iii) increased reduced glutathione levels, (iv) elevation in the oncometabolite 2-hydroxyglutarate, and (v) inhibition of fatty-acid dependent respiration. The majority (83%) of metabolic alterations induced by IPC were ablated when SIRT1 was acutely inhibited with splitomicin, and a principle component analysis revealed that metabolic changes in response to IPC were fundamentally different in nature when SIRT1 was inhibited. Furthermore, the protective benefit of IPC was abrogated by eliminating glucose from perfusion media while sustaining normal cardiac function by burning fat, thus indicating that glucose dependency is required for acute IPC. Together, these data suggest that SIRT1 signaling is required for rapid cardioprotective metabolic adaptation in acute IPC. PMID: 26388263 [PubMed - as supplied by publisher]

Proteomics of the organohalide-respiring Epsilonproteobacterium Sulfurospirillum multivorans adapted to tetrachloroethene and other energy substrates.

Tue, 22/09/2015 - 13:29
Proteomics of the organohalide-respiring Epsilonproteobacterium Sulfurospirillum multivorans adapted to tetrachloroethene and other energy substrates. Sci Rep. 2015;5:13794 Authors: Goris T, Schiffmann CL, Gadkari J, Schubert T, Seifert J, Jehmlich N, von Bergen M, Diekert G Abstract Organohalide respiration is an environmentally important but poorly characterized type of anaerobic respiration. We compared the global proteome of the versatile organohalide-respiring Epsilonproteobacterium Sulfurospirillum multivorans grown with different electron acceptors (fumarate, nitrate, or tetrachloroethene [PCE]). The most significant differences in protein abundance were found for gene products of the organohalide respiration region. This genomic region encodes the corrinoid and FeS cluster containing PCE reductive dehalogenase PceA and other proteins putatively involved in PCE metabolism such as those involved in corrinoid biosynthesis. The latter gene products as well as PceA and a putative quinol dehydrogenase were almost exclusively detected in cells grown with PCE. This finding suggests an electron flow from the electron donor such as formate or pyruvate via the quinone pool and a quinol dehydrogenase to PceA and the terminal electron acceptor PCE. Two putative accessory proteins, an IscU-like protein and a peroxidase-like protein, were detected with PCE only and might be involved in PceA maturation. The proteome of cells grown with pyruvate instead of formate as electron donor indicates a route of electrons from reduced ferredoxin via an Epsilonproteobacterial complex I and the quinone pool to PCE. PMID: 26387727 [PubMed - as supplied by publisher]

A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women.

Tue, 22/09/2015 - 13:29
A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women. Sci Rep. 2015;5:14174 Authors: McMillan A, Rulisa S, Sumarah M, Macklaim JM, Renaud J, Bisanz JE, Gloor GB, Reid G Abstract Bacterial vaginosis (BV) increases transmission of HIV, enhances the risk of preterm labour, and is associated with malodour. Clinical diagnosis often relies on microscopy, which may not reflect the microbiota composition accurately. We use an untargeted metabolomics approach, whereby we normalize the weight of samples prior to analysis, to obtained precise measurements of metabolites in vaginal fluid. We identify biomarkers for BV with high sensitivity and specificity (AUC = 0.99) in a cohort of 131 pregnant and non-pregnant Rwandan women, and demonstrate that the vaginal metabolome is strongly associated with bacterial diversity. Metabolites associated with high diversity and clinical BV include 2-hydroxyisovalerate and γ-hydroxybutyrate (GHB), but not succinate, which is produced by both Lactobacillus crispatus and BV-associated anaerobes in vitro. Biomarkers associated with high diversity and clinical BV are independent of pregnancy status, and were validated in a blinded replication cohort from Tanzania (n = 45), where we predicted clinical BV with 91% accuracy. Correlations between the metabolome and microbiota identified Gardnerella vaginalis as a putative producer of GHB, and we demonstrate production by this species in vitro. This work illustrates how changes in community structure alter the chemical composition of the vagina, and identifies highly specific biomarkers for a common condition. PMID: 26387596 [PubMed - as supplied by publisher]

PathVisio 3: an extendable pathway analysis toolbox.

Tue, 22/09/2015 - 13:29
Related Articles PathVisio 3: an extendable pathway analysis toolbox. PLoS Comput Biol. 2015 Feb;11(2):e1004085 Authors: Kutmon M, van Iersel MP, Bohler A, Kelder T, Nunes N, Pico AR, Evelo CT Abstract PathVisio is a commonly used pathway editor, visualization and analysis software. Biological pathways have been used by biologists for many years to describe the detailed steps in biological processes. Those powerful, visual representations help researchers to better understand, share and discuss knowledge. Since the first publication of PathVisio in 2008, the original paper was cited more than 170 times and PathVisio was used in many different biological studies. As an online editor PathVisio is also integrated in the community curated pathway database WikiPathways. Here we present the third version of PathVisio with the newest additions and improvements of the application. The core features of PathVisio are pathway drawing, advanced data visualization and pathway statistics. Additionally, PathVisio 3 introduces a new powerful extension systems that allows other developers to contribute additional functionality in form of plugins without changing the core application. PathVisio can be downloaded from http://www.pathvisio.org and in 2014 PathVisio 3 has been downloaded over 5,500 times. There are already more than 15 plugins available in the central plugin repository. PathVisio is a freely available, open-source tool published under the Apache 2.0 license (http://www.apache.org/licenses/LICENSE-2.0). It is implemented in Java and thus runs on all major operating systems. The code repository is available at http://svn.bigcat.unimaas.nl/pathvisio. The support mailing list for users is available on https://groups.google.com/forum/#!forum/wikipathways-discuss and for developers on https://groups.google.com/forum/#!forum/wikipathways-devel. PMID: 25706687 [PubMed - indexed for MEDLINE]

Cancer and the gut microbiota: an unexpected link.

Tue, 22/09/2015 - 13:29
Related Articles Cancer and the gut microbiota: an unexpected link. Sci Transl Med. 2015 Jan 21;7(271):271ps1 Authors: Zitvogel L, Galluzzi L, Viaud S, Vétizou M, Daillère R, Merad M, Kroemer G Abstract Changes in the interactions among the gut microbiota, intestinal epithelium, and host immune system are associated with many diseases, including cancer. We discuss how environmental factors infuence this cross-talk during oncogenesis and tumor progression and how manipulations of the gut microbiota might improve the clinical activity of anticancer agents. PMID: 25609166 [PubMed - indexed for MEDLINE]

A U-system approach for predicting metabolic behaviors and responses based on an alleged metabolic reaction network.

Tue, 22/09/2015 - 13:29
Related Articles A U-system approach for predicting metabolic behaviors and responses based on an alleged metabolic reaction network. BMC Syst Biol. 2014;8 Suppl 5:S4 Authors: Sriyudthsak K, Sawada Y, Chiba Y, Yamashita Y, Kanaya S, Onouchi H, Fujiwara T, Naito S, Voit EO, Shiraishi F, Hirai MY Abstract BACKGROUND: Progress in systems biology offers sophisticated approaches toward a comprehensive understanding of biological systems. Yet, computational analyses are held back due to difficulties in determining suitable model parameter values from experimental data which naturally are subject to biological fluctuations. The data may also be corrupted by experimental uncertainties and sometimes do not contain all information regarding variables that cannot be measured for technical reasons. RESULTS: We show here a streamlined approach for the construction of a coarse model that allows us to set up dynamic models with minimal input information. The approach uses a hybrid between a pure mass action system and a generalized mass action (GMA) system in the framework of biochemical systems theory (BST) with rate constants of 1, normal kinetic orders of 1, and -0.5 and 0.5 for inhibitory and activating effects, named Unity (U)-system. The U-system model does not necessarily fit all data well but is often sufficient for predicting metabolic behavior of metabolites which cannot be simultaneously measured, identifying inconsistencies between experimental data and the assumed underlying pathway structure, as well as predicting system responses to a modification of gene or enzyme. The U-system approach was validated with small, generic systems and implemented to model a large-scale metabolic reaction network of a higher plant, Arabidopsis. The dynamic behaviors obtained by predictive simulations agreed with actually available metabolomic time-series data, identified probable errors in the experimental datasets, and estimated probable behavior of unmeasurable metabolites in a qualitative manner. The model could also predict metabolic responses of Arabidopsis with altered network structures due to genetic modification. CONCLUSIONS: The U-system approach can effectively predict metabolic behaviors and responses based on structures of an alleged metabolic reaction network. Thus, it can be a useful first-line tool of data analysis, model diagnostics and aid the design of next-step experiments. PMID: 25559748 [PubMed - indexed for MEDLINE]

Transgenic American chestnuts show enhanced blight resistance and transmit the trait to T1 progeny.

Tue, 22/09/2015 - 13:29
Related Articles Transgenic American chestnuts show enhanced blight resistance and transmit the trait to T1 progeny. Plant Sci. 2014 Nov;228:88-97 Authors: Newhouse AE, Polin-McGuigan LD, Baier KA, Valletta KE, Rottmann WH, Tschaplinski TJ, Maynard CA, Powell WA Abstract American chestnut (Castanea dentata) is a classic example of a native keystone species that was nearly eradicated by an introduced fungal pathogen. This report describes progress made toward producing a fully American chestnut tree with enhanced resistance to the blight fungus (Cryphonectria parasitica). The transgenic American chestnut 'Darling4,' produced through an Agrobacterium co-transformation procedure to express a wheat oxalate oxidase gene driven by the VspB vascular promoter, shows enhanced blight resistance at a level intermediate between susceptible American chestnut and resistant Chinese chestnut (Castanea mollissima). Enhanced resistance was identified first with a leaf-inoculation assay using young chestnuts grown indoors, and confirmed with traditional stem inoculations on 3- and 4-year-old field-grown trees. Pollen from 'Darling4' and other events was used to produce transgenic T1 seedlings, which also expressed the enhanced resistance trait in leaf assays. Outcrossed transgenic seedlings have several advantages over tissue-cultured plantlets, including increased genetic diversity and faster initial growth. This represents a major step toward the restoration of the majestic American chestnut. PMID: 25438789 [PubMed - indexed for MEDLINE]

The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling.

Tue, 22/09/2015 - 13:29
Related Articles The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling. Clin Cancer Res. 2015 Jan 1;21(1):193-200 Authors: Wen CP, Zhang F, Liang D, Wen C, Gu J, Skinner H, Chow WH, Ye Y, Pu X, Hildebrandt MA, Huang M, Chen CH, Hsiung CA, Tsai MK, Tsao CK, Lippman SM, Wu X Abstract PURPOSE: We aimed to identify serum metabolites as potential valuable biomarkers for lung cancer and to improve risk stratification in smokers. EXPERIMENTAL DESIGN: We performed global metabolomic profiling followed by targeted validation of individual metabolites in a case-control design of 386 lung cancer cases and 193 matched controls. We then validated bilirubin, which consistently showed significant differential levels in cases and controls, as a risk marker for lung cancer incidence and mortality in a large prospective cohort composed of 425,660 participants. RESULTS: Through global metabolomic profiling and following targeted validation, bilirubin levels consistently showed a statistically significant difference among healthy controls and lung cancer cases. In the prospective cohort, the inverse association was only seen in male smokers, regardless of smoking pack-years and intensity. Compared with male smokers in the highest bilirubin group (>1 mg/dL), those in the lowest bilirubin group (<0.75 mg/dL) had 55% and 66% increase in risks of lung cancer incidence and mortality, respectively. For every 0.1 mg/dL decrease of bilirubin, the risks for lung cancer incidence and mortality increased by 5% and 6% in male smokers, respectively (both P < 0.001). There was a significant interaction between low serum bilirubin level and smoking on lung cancer risk (Pinteraction = 0.001). CONCLUSION: Low levels of serum bilirubin are associated with higher risks of lung cancer incidence and mortality in male smokers and can be used to identify higher risk smokers for lung cancer. PMID: 25336700 [PubMed - indexed for MEDLINE]

Sulfate-reducing bacteria mediate thionation of diphenylarsinic acid under anaerobic conditions.

Tue, 22/09/2015 - 13:29
Related Articles Sulfate-reducing bacteria mediate thionation of diphenylarsinic acid under anaerobic conditions. Biodegradation. 2015 Feb;26(1):29-38 Authors: Guan L, Shiiya A, Hisatomi S, Fujii K, Nonaka M, Harada N Abstract Diphenylarsinic acid (DPAA) is often found as a toxic intermediate metabolite of diphenylchloroarsine or diphenylcyanoarsine that were produced as chemical warfare agents and were buried in soil after the World Wars. In our previous study Guan et al. (J Hazard Mater 241-242:355-362, 2012), after application of sulfate and carbon sources, anaerobic transformation of DPAA in soil was enhanced with the production of diphenylthioarsinic acid (DPTAA) as a main metabolite. This study aimed to isolate and characterize anaerobic soil microorganisms responsible for the metabolism of DPAA. First, we obtained four microbial consortia capable of transforming DPAA to DPTAA at a high transformation rate of more than 80% after 4 weeks of incubation. Sequencing for the bacterial 16S rRNA gene clone libraries constructed from the consortia revealed that all the positive consortia contained Desulfotomaculum acetoxidans species. In contrast, the absence of dissimilatory sulfite reductase gene (dsrAB) which is unique to sulfate-reducing bacteria was confirmed in the negative consortia showing no DPAA reduction. Finally, strain DEA14 showing transformation of DPAA to DPTAA was isolated from one of the positive consortia. The isolate was assigned to D. acetoxidans based on the partial 16S rDNA sequence analysis. Thionation of DPAA was also carried out in a pure culture of a known sulfate-reducing bacterial strain, Desulfovibrio aerotolerans JCM 12613(T). These facts indicate that sulfate-reducing bacteria are microorganisms responsible for the transformation of DPAA to DPTAA under anaerobic conditions. PMID: 25228086 [PubMed - indexed for MEDLINE]

Negative prognostic value of high levels of intracellular poly (ADP-ribose) in non-small cell lung cancer.

Mon, 21/09/2015 - 14:42
Related Articles Negative prognostic value of high levels of intracellular poly (ADP-ribose) in non-small cell lung cancer. Ann Oncol. 2015 Sep 19; Authors: Michels J, Adam J, Goubar A, Obrist F, Damotte D, Robin A, Alifano M, Vitale I, Olaussen KA, Girard P, Cremer I, Castedo M, Soria JC, Kroemer G Abstract BACKGROUND: Cisplatin-resistant non-small cell lung cancer (NSCLC) cells are often characterized by alterations in vitamin B-related metabolic processes, including the overexpression and hyperactivation of poly(ADP-ribose) polymerase 1 (PARP1) and the down-regulation of pyridoxal kinase (PDXK), correlating with elevated apoptosis resistance. Low PDXK expression is an established negative prognostic factor in NSCLC. PATIENTS AND METHODS: We determined by immunohistochemistry the expression of PARP1 and the level of its product, poly(ADP-ribose) (PAR) in two independent cohorts of patients with resected NSCLC. RESULTS: Intratumoral high levels (above median) of PAR (but not PARP1 protein levels) had a negative prognostic impact in both the training (92 stage I subjects) and validation (133 stage I and II subjects) cohorts, as determined by univariate and multivariate analyses. The simultaneous assessment of PAR and PDXK protein levels improved risk stratification. CONCLUSION: NSCLC patients with high intratumoral PARP1 activity (i.e., elevated PAR levels above median) and low PDXK expression (below median) had, a dismal prognosis, while patients with low PARP1 activity and high PDXK expression had a favourable outcome. Altogether, these results underscore the clinical potential and possible therapeutic relevance of these biomarkers. PMID: 26387143 [PubMed - as supplied by publisher]

Systematic analysis of rice (Oryza sativa) metabolic responses to herbivory.

Sun, 20/09/2015 - 13:17
Systematic analysis of rice (Oryza sativa) metabolic responses to herbivory. Plant Cell Environ. 2015 Sep 19; Authors: Alamgir KM, Hojo Y, Christeller JT, Fukumoto K, Isshiki R, Shinya T, Baldwin IT, Galis I Abstract Plants defend against attack from herbivores by direct and indirect defense mechanisms mediated by the accumulation of phytoalexins and release of volatile signals, respectively. While the defensive arsenals of some plants, such as tobacco and Arabidopsis are well known, most of rice's (Oryza sativa) defense metabolites and their effectiveness against herbivores remain uncharacterized. Here, we used a non-biased metabolomics approach to identify many novel herbivory-regulated metabolic signatures in rice. Most were up-regulated by herbivore attack while only a few were suppressed. Two of the most prominent up-regulated signatures were characterized as phenolamides (PAs), p-coumaroylputrescine and feruloylputrescine. PAs accumulated in response to attack by both chewing insects, i.e. feeding of the lawn armyworm (Spodoptera mauritia) and the rice skipper (Parnara guttata) larvae, and the attack of the sucking insect, the brown planthopper (Nilaparvata lugens, BPH). In bioassays, BPH insects feeding on 15% sugar solution containing p-coumaroylputrescine or feruloylputrescine, at concentrations similar to those elicited by heavy BPH attack in rice, had a higher mortality compared to those feeding on sugar diet alone. Our results highlight PAs as a rapidly expanding new group of plant defense metabolites that are elicited by herbivore attack, and deter herbivores in rice and other plants. PMID: 26386366 [PubMed - as supplied by publisher]

RhizoFlowCell system reveals early effects of micropollutants on aquatic plant rhizosphere.

Sun, 20/09/2015 - 13:17
RhizoFlowCell system reveals early effects of micropollutants on aquatic plant rhizosphere. Environ Pollut. 2015 Sep 16;207:205-210 Authors: Mynampati KC, Lee YJ, Wijdeveld A, Reuben S, Samavedham L, Kjelleberg S, Swarup S Abstract In aquatic systems, one of the non-destructive ways to quantify toxicity of contaminants to plants is to monitor changes in root exudation patterns. In aquatic conditions, monitoring and quantifying such changes are currently challenging because of dilution of root exudates in water phase and lack of suitable instrumentation to measure them. Exposure to pollutants would not only change the plant exudation, but also affect the microbial communities that surround the root zone, thereby changing the metabolic profiles of the rhizosphere. This study aims at developing a device, the RhizoFlowCell, which can quantify metabolic response of plants, as well as changes in the microbial communities, to give an estimate of the stress to which the rhizosphere is exposed. The usefulness of RhizoFlowCell is demonstrated using naphthalene as a test pollutant. Results show that RhizoFlowCell system is useful in quantifying the dynamic metabolic response of aquatic rhizosphere to determine ecosystem health. PMID: 26386206 [PubMed - as supplied by publisher]

Metabolic responses to Lactobacillus plantarum contamination or bacteriophage treatment in Saccharomyces cerevisiae using a GC-MS-based metabolomics approach.

Sun, 20/09/2015 - 13:17
Metabolic responses to Lactobacillus plantarum contamination or bacteriophage treatment in Saccharomyces cerevisiae using a GC-MS-based metabolomics approach. World J Microbiol Biotechnol. 2015 Sep 18; Authors: Cui FX, Zhang RM, Liu HQ, Wang YF, Li H Abstract Bacteriophage can be used as a potential alternative agent for controlling Lactobacillus plantarum contamination during bioethanol production. However, how Saccharomyces cerevisiae respond against contaminative L. plantarum or added bacteriophage remains to be fully understood. In this study, gas chromatography-mass spectrometry and a multivariate analysis were employed to investigate the intracellular biochemical changes in S. cerevisiae cells that were elicited by L. plantarum contamination or bacteriophage treatment. The intracellular metabolite profiles originating from different groups were unique and could be distinguished with the aid of principal component analysis. Moreover, partial least-squares-discriminant analysis revealed a group classification and pairwise discrimination, and 13 differential metabolites with variable importance in the projection value greater than 1 were identified. The metabolic relevance of these compounds in the response of S. cerevisiae to L. plantarum contamination or bacteriophage treatment was discussed. Besides generating lactic acid and competing for nutrients or living space, L. plantarum contamination might also inhibit the growth of S. cerevisiae through regulating the glycolysis in S. cerevisiae. Moreover, increased concentrations of monounsaturated fatty acids secondary to bacteriophage treatment might lead to more membrane fluidity and promote the cell viability of S. cerevisiae. PMID: 26385547 [PubMed - as supplied by publisher]

Vaginal microbiome and metabolome highlight specific signatures of bacterial vaginosis.

Sun, 20/09/2015 - 13:17
Vaginal microbiome and metabolome highlight specific signatures of bacterial vaginosis. Eur J Clin Microbiol Infect Dis. 2015 Sep 18; Authors: Vitali B, Cruciani F, Picone G, Parolin C, Donders G, Laghi L Abstract In this study, we sought to find novel bacterial and metabolic hallmarks for bacterial vaginosis (BV). We studied the vaginal microbiome and metabolome of vaginal fluids from BV-affected patients (n = 43) and healthy controls (n = 37) by means of an integrated approach based on quantitative polymerase chain reaction (qPCR) and proton nuclear magnetic resonance ((1)H-NMR). The correlations between the clinical condition and vaginal bacterial communities were investigated by principal component analysis (PCA). To define the metabolomics signatures of BV, 100 discriminant analysis by projection on latent structure (PLS-DA) models were calculated. Bacterial signatures distinguishing the health condition and BV were identified by qPCR. Lactobacillus crispatus strongly featured the healthy vagina, while increased concentrations of Prevotella, Atopobium and Mycoplasma hominis specifically marked the infection. (1)H-NMR analysis has led to the identification and quantification of 17 previously unreported molecules. BV was associated with changes in the concentration of metabolites belonging to the families of amines, organic acids, short chain fatty acids, amino acids, nitrogenous bases and monosaccharides. In particular, maltose, kynurenine and NAD(+) primarily characterised the healthy status, while nicotinate, malonate and acetate were the best metabolic hallmarks of BV. This study helps to better understand the role of the vaginal microbiota and metabolome in the development of BV infection. We propose a molecular approach for the diagnosis of BV based on quantitative detection in the vaginal fluids of Atopobium, Prevotella and M. hominis, and nicotinate, malonate and acetate by combining qPCR and (1)H-NMR. PMID: 26385347 [PubMed - as supplied by publisher]

Metabolic responses of the isopod Porcellionides pruinosus to nickel exposure assessed by (1)H NMR metabolomics.

Sun, 20/09/2015 - 13:17
Metabolic responses of the isopod Porcellionides pruinosus to nickel exposure assessed by (1)H NMR metabolomics. J Proteomics. 2015 Sep 15; Authors: Ferreira NG, Saborano R, Morgado R, Cardoso DN, Rocha CM, Soares AM, Loureiro S, Duarte IF PMID: 26385004 [PubMed - as supplied by publisher]

Physiological changes due to mild cooling in healthy lean males of white Caucasian and South Asian descent: a metabolomics study.

Sun, 20/09/2015 - 13:17
Physiological changes due to mild cooling in healthy lean males of white Caucasian and South Asian descent: a metabolomics study. Arch Biochem Biophys. 2015 Sep 15; Authors: Nahon KJ, Boon MR, Bakker LE, Prehn C, Adamski J, Jazet IM, van Dijk KW, Rensen PC, Mook-Kanamori DO Abstract During mild cold exposure, non-shivering thermogenesis increases to maintain core body temperature by increasing utilization of substrates, especially fatty acids (FA), ultimately affecting lipid-associated metabolites. We aimed to investigate whether mild cooling induces changes in other metabolites and whether this response differs between white Caucasians and South Asians, who have a disadvantageous metabolic phenotype. 12 lean male Dutch white Caucasians and 12 matched Dutch South Asians were exposed to mild cold. Before and after 100 minutes exposure, serum samples were collected for analysis of 163 metabolites and 27 derived parameters using high throughput metabolomics. The overall response to mild cooling between both ethnicities was not different, therefore the data were pooled. After Bonferroni correction, mild cooling significantly changed 44 of 190 (23%) metabolic parameters. Specifically, cooling increased 19 phosphatidylcholine (PC) species, only those containing very long chain FAs, and increased the total class of PC containing mono-unsaturated FAs (+12.5%). Furthermore, cooling increased 10 sphingomyelin species as well as the amino acids glutamine (+18.7%), glycine (+11.6%) and histidine (+10.6%), and decreased short-chain (C3 and C4) acylcarnitines (-17.1% and -19.4%, respectively). In conclusion, mild cooling elicits substantial effects on serum metabolites in healthy males, irrespective of white Caucasian or South Asian ethnicity. PMID: 26384768 [PubMed - as supplied by publisher]

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