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

Genomics and Metabolomics in Obesity and Type 2 Diabetes.

Sat, 18/06/2016 - 13:00
Genomics and Metabolomics in Obesity and Type 2 Diabetes. J Diabetes Res. 2016;2016:9415645 Authors: Kretowski A, Ruperez FJ, Ciborowski M PMID: 27314051 [PubMed - in process]

Associations between plasma branched-chain amino acids, β-aminoisobutyric acid and body composition.

Sat, 18/06/2016 - 13:00
Associations between plasma branched-chain amino acids, β-aminoisobutyric acid and body composition. J Nutr Sci. 2016;5:e6 Authors: Rietman A, Stanley TL, Clish C, Mootha V, Mensink M, Grinspoon SK, Makimura H Abstract Plasma branched-chain amino acids (BCAA) are elevated in obesity and associated with increased cardiometabolic risk. β-Aminoisobutyric acid (B-AIBA), a recently identified small molecule metabolite, is associated with decreased cardiometabolic risk. Therefore, we investigated the association of BCAA and B-AIBA with each other and with detailed body composition parameters, including abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). A cross-sectional study was carried out with lean (n 15) and obese (n 33) men and women. Detailed metabolic evaluations, including measures of body composition, insulin sensitivity and plasma metabolomics were completed. Plasma BCAA were higher (1·6 (se 0·08) (×10(7)) v. 1·3 (se 0·06) (×10(7)) arbitrary units; P = 0·005) in obese v. lean subjects. BCAA were positively associated with VAT (R 0·49; P = 0·0006) and trended to an association with SAT (R 0·29; P = 0·052). The association between BCAA and VAT, but not SAT, remained significant after controlling for age, sex and race on multivariate modelling (P < 0·05). BCAA were also associated with parameters of insulin sensitivity (Matsuda index: R -0·50, P = 0·0004; glucose AUC: R 0·53, P < 0·001). BCAA were not associated with B-AIBA (R -0·04; P = 0·79). B-AIBA was negatively associated with SAT (R -0·37; P = 0·01) but only trended to an association with VAT (R 0·27; P = 0·07). However, neither relationship remained significant after multivariate modelling (P > 0·05). Plasma B-AIBA was associated with parameters of insulin sensitivity (Matsuda index R 0·36, P = 0·01; glucose AUC: R -0·30, P = 0·04). Plasma BCAA levels were positively correlated with VAT and markers of insulin resistance. The results suggest a possible complex role of adipose tissue in BCAA homeostasis and insulin resistance. PMID: 27313851 [PubMed]

The LINA Study: Higher Sensitivity of Infant Compared to Maternal Eosinophil/Basophil Progenitors to Indoor Chemical Exposures.

Sat, 18/06/2016 - 13:00
The LINA Study: Higher Sensitivity of Infant Compared to Maternal Eosinophil/Basophil Progenitors to Indoor Chemical Exposures. J Environ Public Health. 2016;2016:5293932 Authors: Hörnig F, Kohajda T, Röder S, Herberth G, von Bergen M, Borte M, Diez U, Rolle-Kampczyk U, Simon JC, Denburg JA, Lehmann I, Junge KM Abstract Purpose. Enhanced eosinophil/basophil (Eo/B) progenitor cell levels are known to be associated with allergic inflammation and atopy risk. The aim of the present study was to investigate the influence of different indoor exposures on the recruitment and differentiation of Eo/B progenitors in mother-child pairs. Methods. In 68 mother-child pairs of the LINA study peripheral blood mononuclear cells were used to assess Eo/B colony forming units (CFUs). Information about disease outcomes and indoor exposures was obtained from questionnaires. Indoor concentrations of volatile organic compounds (VOCs) were measured by passive sampling. Results. Infant's Eo/B CFUs were positively associated with exposure to tobacco smoke, disinfectants, or VOCs. In contrast, for maternal Eo/B CFUs, only a few associations were seen. Higher numbers of infant Eo/B CFUs were observed in children with wheezing symptoms within the second year of life. Conclusions. We demonstrate that infant's hematopoietic cells seem to respond with more sensitivity to environmental exposure compared to maternal cells. At least in infants, an activation of these hematopoietic cells by environmental exposure could contribute to an enhanced risk for the development of respiratory outcomes. PMID: 27313631 [PubMed - in process]

Application of a Smartphone Metabolomics Platform to the Authentication of Schisandra sinensis.

Sat, 18/06/2016 - 13:00
Application of a Smartphone Metabolomics Platform to the Authentication of Schisandra sinensis. Phytochem Anal. 2016 May;27(3-4):199-205 Authors: Kwon HN, Phan HD, Xu WJ, Ko YJ, Park S Abstract INTRODUCTION: Herbal medicines have been used for a long time all around the world. Since the quality of herbal preparations depends on the source of herbal materials, there has been a strong need to develop methods to correctly identify the origin of materials. OBJECTIVE: To develop a smartphone metabolomics platform as a simpler and low-cost alternative for the identification of herbal material source. METHODOLOGY: Schisandra sinensis extracts from Korea and China were prepared. The visible spectra of all samples were measured by a smartphone spectrometer platform. This platform included all the necessary measures built-in for the metabolomics research: data acquisition, processing, chemometric analysis and visualisation of the results. The result of the smartphone metabolomics platform was compared to that of NMR-based metabolomics, suggesting the feasibility of smartphone platform in metabolomics research. RESULTS: The smartphone metabolomics platform gave similar results to the NMR method, showing good separation between Korean and Chinese materials and correct predictability for all test samples. CONCLUSION: With its accuracy and advantages of affordability, user-friendliness, and portability, the smartphone metabolomics platform could be applied to the authentication of other medicinal plants. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27313157 [PubMed - in process]

In situ Identification of Labile Precursor Compounds and their Short-lived Intermediates in Plants using in vivo Nanospray High-resolution Mass Spectrometry.

Sat, 18/06/2016 - 13:00
In situ Identification of Labile Precursor Compounds and their Short-lived Intermediates in Plants using in vivo Nanospray High-resolution Mass Spectrometry. Phytochem Anal. 2016 May;27(3-4):184-90 Authors: Chang Q, Peng Y, Shi B, Dan C, Yang Y, Shuai Q Abstract INTRODUCTION: Many secondary metabolites in plants are labile compounds which under environmental stress, are difficult to detect and track due to the lack of rapid in situ identification techniques, making plant metabolomics research difficult. Therefore, developing a reliable analytical method for rapid in situ identification of labile compounds and their short-lived intermediates in plants is of great importance. OBJECTIVE: To develop under atmospheric pressure, a rapid in situ method for effective identification of labile compounds and their short-lived intermediates in fresh plants. METHODOLOGY: An in vivo nanospray high-resolution mass spectrometry (HR-MS) method was used for rapid capture of labile compounds and their short-lived intermediates in plants. A quartz capillary was partially inserted into fresh plant tissues, and the liquid flowed out through the capillary tube owing to the capillary effect. A high direct current (d.c.) voltage was applied to the plant to generate a spray of charged droplets from the tip of the capillary carrying bioactive molecules toward the inlet of mass spectrometer for full-scan and MS/MS analysis. RESULTS: Many labile compounds and short-lived intermediates were identified via this method: including glucosinolates and their short-lived intermediates (existing for only 10 s) in Raphanus sativus roots, alliin and its conversion intermediate (existing for 20 s) in Allium sativum and labile precursor compound chlorogenic acid in Malus pumila Mill. CONCLUSION: The method is an effective approach for in situ identification of internal labile compounds and their short-lived intermediates in fresh plants and it can be used as an auxiliary tool to explore the degradation mechanisms of new labile plant compounds. Copyright © 2016 John Wiley & Sons, Ltd. PMID: 27313155 [PubMed - in process]

Elucidation of ethanol tolerance mechanisms in Saccharomyces cerevisiae by global metabolite profiling.

Sat, 18/06/2016 - 13:00
Elucidation of ethanol tolerance mechanisms in Saccharomyces cerevisiae by global metabolite profiling. Biotechnol J. 2016 Jun 17; Authors: Kim S, Kim J, Song JH, Jung YH, Choi IS, Choi W, Park YC, Seo JH, Kim KH Abstract Ethanol, the major fermentation product of yeast, is a stress factor in yeast. We previously constructed an ethanol-tolerant mutant yeast iETS3 by using the global transcriptional machinery engineering. However, the ethanol-tolerance mechanism has not been systematically investigated. In this study, global metabolite profiling was carried out, mainly by gas chromatography/time-of-flight mass spectrometry (GC/TOF MS), to investigate the mechanisms of ethanol tolerance in iETS3. A total of 108 intracellular metabolites were identified by GC/TOF MS and high performance liquid chromatography, and these metabolites were mostly intermediates of the central carbon metabolism. The metabolite profiles of iETS3 and BY4741, cultured with or without ethanol, were significantly different based on principal component and hierarchical clustering analyses. Our metabolomic analyses identified the compositional changes in cell membranes and the activation of glutamate metabolism and the trehalose synthetic pathway as the possible mechanisms for the ethanol tolerance. These metabolic traits can be considered possible targets for further improvement of ethanol tolerance in the mutant. For example, the KGD1 deletion mutant, with up-regulated glutamate metabolism, showed increased tolerance to ethanol. This study has demonstrated that metabolomics can be a useful tool for strain improvement and phenotypic analysis of microorganisms under stress. PMID: 27313052 [PubMed - as supplied by publisher]

Biodiversity in marine invertebrate responses to acute warming revealed by a comparative multi-omics approach.

Sat, 18/06/2016 - 13:00
Biodiversity in marine invertebrate responses to acute warming revealed by a comparative multi-omics approach. Glob Chang Biol. 2016 Jun 17; Authors: Clark MS, Sommer U, Sihra JK, Thorne MA, Morley SA, King M, Viant MR, Peck LS Abstract Understanding species' responses to environmental change underpins our abilities to make predictions on future biodiversity under any range of scenarios. In spite of the huge biodiversity in most ecosystems, a model species approach is often taken in environmental studies. To date, we still do not know how many species we need to study to input into models and inform on ecosystem-level responses to change. In this study, we tested current paradigms on factors setting thermal limits by investigating the acute warming response of six Antarctic marine invertebrates: a crustacean Paraceradocus miersi, a brachiopod Liothyrella uva, two bivalve molluscs, Laternula elliptica, Aequiyoldia eightsii, a gastropod mollusc Marseniopsis mollis and an echinoderm Cucumaria georgiana. Each species was warmed at the rate of 1 °C h(-1) and taken to the same physiological end point (just prior to heat coma). Their molecular responses were evaluated using complementary metabolomics and transcriptomics approaches with the aim of discovering the underlying mechanisms of their resilience or sensitivity to warming. The responses were species-specific; only two showed accumulation of anaerobic end products and three exhibited the classical heat shock response with expression of HSP70 transcripts. These diverse cellular measures did not directly correlate with resilience to heat stress and suggested that each species may have a different critical point of failure. Thus, one unifying molecular mechanism underpinning response to warming could not be assigned, and no overarching paradigm was supported. This biodiversity in response makes future ecosystems predictions extremely challenging, as we clearly need to develop a macrophysiology-type approach to cellular evaluations of the environmental stress response, studying a range of well-rationalized members from different community levels and of different phylogenetic origins rather than extrapolating from one or two arbitrary model species. PMID: 27312151 [PubMed - as supplied by publisher]

metabolomics; +19 new citations

Fri, 17/06/2016 - 12:29
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2016/06/17PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.

Thu, 16/06/2016 - 14:40
Related Articles Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice. Cell Metab. 2016 Jun 14;23(6):1093-1112 Authors: Mitchell SJ, Madrigal-Matute J, Scheibye-Knudsen M, Fang E, Aon M, González-Reyes JA, Cortassa S, Kaushik S, Gonzalez-Freire M, Patel B, Wahl D, Ali A, Calvo-Rubio M, Burón MI, Guiterrez V, Ward TM, Palacios HH, Cai H, Frederick DW, Hine C, Broeskamp F, Habering L, Dawson J, Beasley TM, Wan J, Ikeno Y, Hubbard G, Becker KG, Zhang Y, Bohr VA, Longo DL, Navas P, Ferrucci L, Sinclair DA, Cohen P, Egan JM, Mitchell JR, Baur JA, Allison DB, Anson RM, Villalba JM, Madeo F, Cuervo AM, Pearson KJ, Ingram DK, Bernier M, de Cabo R Abstract Calorie restriction (CR) is the most robust non-genetic intervention to delay aging. However, there are a number of emerging experimental variables that alter CR responses. We investigated the role of sex, strain, and level of CR on health and survival in mice. CR did not always correlate with lifespan extension, although it consistently improved health across strains and sexes. Transcriptional and metabolomics changes driven by CR in liver indicated anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. CR prevented age-associated decline in the liver proteostasis network while increasing mitochondrial number, preserving mitochondrial ultrastructure and function with age. Abrogation of mitochondrial function negated life-prolonging effects of CR in yeast and worms. Our data illustrate the complexity of CR in the context of aging, with a clear separation of outcomes related to health and survival, highlighting complexities of translation of CR into human interventions. PMID: 27304509 [PubMed - as supplied by publisher]

Salinity tolerance is related to cyanide-resistant alternative respiration in Medicago truncatula under sudden severe stress.

Thu, 16/06/2016 - 14:40
Related Articles Salinity tolerance is related to cyanide-resistant alternative respiration in Medicago truncatula under sudden severe stress. Plant Cell Environ. 2016 Jun 15; Authors: Fernández Del-Saz N, Florez-Sarasa I, Clemente-Moreno MJ, Mhadhbi H, Flexas J, Fernie AR, Ribas-Carbó M Abstract Salt respiration is defined as the increase of respiration under early salt stress. However, the response of respiration varies depending on the degree of salt tolerance and salt stress. It has been hypothesized that the activity of the alternative pathway may increase preventing over-reduction of the ubiquinone pool in response to salinity, which in turn can increase respiration. Three genotypes of Medicago truncatula are reputed as differently responsive to salinity: TN1.11, A17 and TN6.18. We used the oxygen-isotope fractionation technique to study the in vivo respiratory activities of the cytochrome oxidase pathway (COP) and the alternative oxidase pathway (AOP) in leaves and roots of these genotypes treated with severe salt stress (300 mM) during 1 and 3 days. In parallel, AOX capacity, gas exchange measurements, relative water content and metabolomics were determined in control and treated plants. Our study shows for first time that salt respiration is induced by the triggered AOP in response to salinity. Moreover, this phenomenon coincides with increased levels of metabolites such as amino and organic acids, and is shown to be related with higher photosynthetic rate and water content in TN6.18. PMID: 27304415 [PubMed - as supplied by publisher]

Microbiome-Metabolome Responses in the Cecum and Colon of Pig to a High Resistant Starch Diet.

Thu, 16/06/2016 - 14:40
Related Articles Microbiome-Metabolome Responses in the Cecum and Colon of Pig to a High Resistant Starch Diet. Front Microbiol. 2016;7:779 Authors: Sun Y, Su Y, Zhu W Abstract Currently, knowledge about the impact of long-term intake of high resistant starch diet on pig hindgut microbiota and metabolite profile is limited. In this study, a combination of the pyrosequencing and the mass spectrometry (MS)-based metabolomics techniques were used to investigate the effects of a raw potato starch (RPS, high in resistant starch) diet on microbial composition and microbial metabolites in the hindgut of pig. The results showed that Coprococcus, Ruminococcus, and Turicibacter increased significantly, while Sarcina and Clostridium decreased in relative abundances in the hindgut of pigs fed RPS. The metabolimic analysis revealed that RPS significantly affected starch and sucrose metabolites, amino acid turnover or protein biosynthesis, lipid metabolites, glycolysis, the pentose phosphate pathway, inositol phosphate metabolism, and nucleotide metabolism. Furthermore, a Pearson's correlation analysis showed that Ruminococcus and Coprococcus were positively correlated with glucose-6-phosphate, maltose, arachidonic acid, 9, 12-octadecadienoic acid, oleic acid, phosphate, but negatively correlated with α-aminobutyric acid. However, the correlation of Clostridium and Sarcina with these compounds was in the opposite direction. The results suggest that RPS not only alters the composition of the gut microbial community but also modulates the metabolic pathway of microbial metabolism, which may further affect the hindgut health of the host. PMID: 27303373 [PubMed]

Metabolomics of aging requires large-scale longitudinal studies with replication.

Thu, 16/06/2016 - 14:40
Related Articles Metabolomics of aging requires large-scale longitudinal studies with replication. Proc Natl Acad Sci U S A. 2016 Jun 14; Authors: Mäkinen VP, Ala-Korpela M PMID: 27303027 [PubMed - as supplied by publisher]

Reply to Mäkinen and Ala-Korpela: Small-scale but accurate metabolomics with high reproducibility for identifying age-related blood metabolites.

Thu, 16/06/2016 - 14:40
Related Articles Reply to Mäkinen and Ala-Korpela: Small-scale but accurate metabolomics with high reproducibility for identifying age-related blood metabolites. Proc Natl Acad Sci U S A. 2016 Jun 14; Authors: Kondoh H, Yanagida M PMID: 27303026 [PubMed - as supplied by publisher]

Longitudinal monitoring of immunoglobulin A glycosylation during pregnancy by simultaneous MALDI-FTICR-MS analysis of N- and O-glycopeptides.

Thu, 16/06/2016 - 14:40
Related Articles Longitudinal monitoring of immunoglobulin A glycosylation during pregnancy by simultaneous MALDI-FTICR-MS analysis of N- and O-glycopeptides. Sci Rep. 2016;6:27955 Authors: Bondt A, Nicolardi S, Jansen BC, Stavenhagen K, Blank D, Kammeijer GS, Kozak RP, Fernandes DL, Hensbergen PJ, Hazes JM, van der Burgt YE, Dolhain RJ, Wuhrer M Abstract Immunoglobulin A (IgA) is a glycoprotein of which altered glycosylation has been associated with several pathologies. Conventional methods for IgA N- and O-glycosylation analysis are tedious, thus limiting such analyses to small sample sizes. Here we present a high-throughput strategy for the simultaneous analysis of serum-derived IgA1 N- and O-glycopeptides using matrix-assisted laser/desorption ionisation Fourier transform ion cyclotron resonance (MALDI-FTICR) mass spectrometry (MS). Six non-fucosylated diantennary complex type glycoforms were detected on the Asn144-containing glycopeptide. Thirteen distinct glycoforms were identified for the Asn340-containing tailpiece glycopeptide, mainly of the diantennary complex type, and low amounts of triantennary glycoforms. Simultaneously with these N-glycopeptides, 53 compositional glycoforms of the hinge region O-glycopeptide were profiled in a single high resolution MALDI-FTICR spectrum. Since many pregnancy associated changes have been recognized for immunoglobulin G, we sought to demonstrate the clinical applicability of this method in a cohort of 29 pregnant women, from whom samples were collected at three time points during pregnancy and three time points after delivery. Pregnancy associated changes of N-glycan bisection were different for IgA1 as compared to IgG-Fc described earlier. We foresee further applications of the developed method for larger patient cohorts to study IgA N- and O-glycosylation changes in pathologies. PMID: 27302155 [PubMed - in process]

LC-MS based metabolomics and chemometrics study of the toxic effects of copper on Saccharomyces cerevisiae.

Thu, 16/06/2016 - 14:40
Related Articles LC-MS based metabolomics and chemometrics study of the toxic effects of copper on Saccharomyces cerevisiae. Metallomics. 2016 Jun 15; Authors: Farrés M, Piña B, Tauler R Abstract Copper containing fungicides are used to protect vineyards from fungal infections. Higher residues of copper in grapes at toxic concentrations are potentially toxic and affect the microorganisms living in vineyards, such as Saccharomyces cerevisiae. In this study, the response of the metabolic profiles of S. cerevisiae at different concentrations of copper sulphate (control, 1 mM, 3 mM and 6 mM) was analysed by liquid chromatography coupled to mass spectrometry (LC-MS) and multivariate curve resolution-alternating least squares (MCR-ALS) using an untargeted metabolomics approach. Peak areas of the MCR-ALS resolved elution profiles in control and in Cu(ii)-treated samples were compared using partial least squares regression (PLSR) and PLS-discriminant analysis (PLS-DA), and the intracellular metabolites best contributing to sample discrimination were selected and identified. Fourteen metabolites showed significant concentration changes upon Cu(ii) exposure, following a dose-response effect. The observed changes were consistent with the expected effects of Cu(ii) toxicity, including oxidative stress and DNA damage. This research confirmed that LC-MS based metabolomics coupled to chemometric methods are a powerful approach for discerning metabolomics changes in S. cerevisiae and for elucidating modes of toxicity of environmental stressors, including heavy metals like Cu(ii). PMID: 27302082 [PubMed - as supplied by publisher]

Fructose promotes growth and antifungal activity of Penicillium citrinum.

Thu, 16/06/2016 - 14:40
Related Articles Fructose promotes growth and antifungal activity of Penicillium citrinum. Protein Cell. 2016 Jun 15; Authors: Wu CW, Wu X, Wen C, Peng B, Peng XX, Chen X, Li H PMID: 27301255 [PubMed - as supplied by publisher]

Proteomic and Metabolomic Analyses Reveal Contrasting Anti-Inflammatory Effects of an Extract of Mucor Racemosus Secondary Metabolites Compared to Dexamethasone.

Thu, 16/06/2016 - 14:40
Related Articles Proteomic and Metabolomic Analyses Reveal Contrasting Anti-Inflammatory Effects of an Extract of Mucor Racemosus Secondary Metabolites Compared to Dexamethasone. PLoS One. 2015;10(10):e0140367 Authors: Meier SM, Muqaku B, Ullmann R, Bileck A, Kreutz D, Mader JC, Knasmüller S, Gerner C Abstract Classical drug assays are often confined to single molecules and targeting single pathways. However, it is also desirable to investigate the effects of complex mixtures on complex systems such as living cells including the natural multitude of signalling pathways. Evidence based on herbal medicine has motivated us to investigate potential beneficial health effects of Mucor racemosus (M rac) extracts. Secondary metabolites of M rac were collected using a good-manufacturing process (GMP) approved production line and a validated manufacturing process, in order to obtain a stable product termed SyCircue (National Drug Code USA: 10424-102). Toxicological studies confirmed that this product does not contain mycotoxins and is non-genotoxic. Potential effects on inflammatory processes were investigated by treating stimulated cells with M rac extracts and the effects were compared to the standard anti-inflammatory drug dexamethasone on the levels of the proteome and metabolome. Using 2D-PAGE, slight anti-inflammatory effects were observed in primary white blood mononuclear cells, which were more pronounced in primary human umbilical vein endothelial cells (HUVECs). Proteome profiling based on nLC-MS/MS analysis of tryptic digests revealed inhibitory effects of M rac extracts on pro-inflammatory cytoplasmic mediators and secreted cytokines and chemokines in these endothelial cells. This finding was confirmed using targeted proteomics, here treatment of stimulated cells with M rac extracts down-regulated the secretion of IL-6, IL-8, CXCL5 and GROA significantly. Finally, the modulating effects of M rac on HUVECs were also confirmed on the level of the metabolome. Several metabolites displayed significant concentration changes upon treatment of inflammatory activated HUVECs with the M rac extract, including spermine and lysophosphatidylcholine acyl C18:0 and sphingomyelin C26:1, while the bulk of measured metabolites remained unaffected. Interestingly, the effects of M rac treatment on lipids were orthogonal to the effect of dexamethasone underlining differences in the overall mode of action. PMID: 26496078 [PubMed - indexed for MEDLINE]

Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study.

Wed, 15/06/2016 - 14:02
Related Articles Maternal Early Pregnancy Serum Metabolomics Profile and Abnormal Vaginal Bleeding as Predictors of Placental Abruption: A Prospective Study. PLoS One. 2016;11(6):e0156755 Authors: Gelaye B, Sumner SJ, McRitchie S, Carlson JE, Ananth CV, Enquobahrie DA, Qiu C, Sorensen TK, Williams MA Abstract BACKGROUND & OBJECTIVE: Placental abruption, an ischemic placental disorder, complicates about 1 in 100 pregnancies, and is an important cause of maternal and perinatal morbidity and mortality worldwide. Metabolomics holds promise for improving the phenotyping, prediction and understanding of pathophysiologic mechanisms of complex clinical disorders including abruption. We sought to evaluate maternal early pregnancy pre-diagnostic serum metabolic profiles and abnormal vaginal bleeding as predictors of abruption later in pregnancy. METHODS: Maternal serum was collected in early pregnancy (mean 16 weeks, range 15 to 22 weeks) from 51 abruption cases and 51 controls. Quantitative targeted metabolic profiles of serum were acquired using electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and the Absolute IDQ® p180 kit. Maternal sociodemographic characteristics and reproductive history were abstracted from medical records. Stepwise logistic regression models were developed to evaluate the extent to which metabolites aid in the prediction of abruption. We evaluated the predictive performance of the set of selected metabolites using a receiver operating characteristics (ROC) curve analysis and area under the curve (AUC). RESULTS: Early pregnancy vaginal bleeding, dodecanoylcarnitine/dodecenoylcarnitine (C12 / C12:1), and phosphatidylcholine acyl-alkyl C 38:1 (PC ae C38:1) strongly predict abruption risk. The AUC for these metabolites alone was 0.68, for early pregnancy vaginal bleeding alone was 0.65, and combined the AUC improved to 0.75 with the addition of quantitative metabolite data (P = 0.003). CONCLUSION: Metabolomic profiles of early pregnancy maternal serum samples in addition to the clinical symptom, vaginal bleeding, may serve as important markers for the prediction of abruption. Larger studies are necessary to corroborate and validate these findings in other cohorts. PMID: 27300725 [PubMed - as supplied by publisher]

A Multiplatform Metabolomics Approach to Characterize Plasma Levels of Phenylalanine and Tyrosine in Phenylketonuria.

Wed, 15/06/2016 - 14:02
Related Articles A Multiplatform Metabolomics Approach to Characterize Plasma Levels of Phenylalanine and Tyrosine in Phenylketonuria. JIMD Rep. 2016 Jun 15; Authors: Blasco H, Veyrat-Durebex C, Bertrand M, Patin F, Labarthe F, Henique H, Emond P, Andres CR, Antar C, Landon C, Nadal-Desbarats L, Maillot F Abstract BACKGROUND: Different pathophysiological mechanisms have been described in phenylketonuria (PKU) but the indirect metabolic consequences of metabolic disorders caused by elevated Phe or low Tyr concentrations remain partially unknown. We used a multiplatform metabolomics approach to evaluate the metabolic signature associated with Phe and Tyr. MATERIAL AND METHODS: We prospectively included 10 PKU adult patients and matched controls. We analysed the metabolome profile using GC-MS (urine), amino-acid analyzer (urine and plasma) and nuclear magnetic resonance spectroscopy (urine). We performed a multivariate analysis from the metabolome (after exclusion of Phe, Tyr and directly derived metabolites) to explain plasma Phe and Tyr concentrations, and the clinical status. Finally, we performed a univariate analysis of the most discriminant metabolites and we identified the associated metabolic pathways. RESULTS: We obtained a metabolic pattern from 118 metabolites and we built excellent multivariate models to explain Phe, Tyr concentrations and PKU diagnosis. Common metabolites of these models were identified: Gln, Arg, succinate and alpha aminobutyric acid. Univariate analysis showed an inverse correlation between Arg, alpha aminobutyric acid and Phe and a positive correlation between Arg, succinate, Gln and Tyr (p < 0.0003). Thus, we highlighted the following pathways: Arg and Pro, Ala, Asp and Glu metabolism. DISCUSSION: We obtain a specific metabolic signature related to Tyr and Phe concentrations. We confirmed the involvement of different pathophysiological mechanisms previously described in PKU such as protein synthesis, energetic metabolism and oxidative stress. The metabolomics approach is relevant to explore PKU pathogenesis. PMID: 27300702 [PubMed - as supplied by publisher]

Metabolic dynamics of Desulfovibrio vulgaris biofilm grown on a steel surface.

Wed, 15/06/2016 - 14:02
Related Articles Metabolic dynamics of Desulfovibrio vulgaris biofilm grown on a steel surface. Biofouling. 2016 Aug;32(7):725-736 Authors: Zhang Y, Pei G, Chen L, Zhang W Abstract In this study, a comparative metabolomics approach combining gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) was applied first between planktonic cells and biofilms and then between pure cultures and biofilms of Desulfovibrio vulgaris. The results revealed that the overall metabolic level of the biofilm cells was down-regulated, especially for metabolites related to the central carbon metabolism, compared to the planktonic cells and the pure culture of D. vulgaris. In addition, pathway enrichment analysis of the 58 metabolites identified by GC-MS showed that fatty acid biosynthesis in the biofilm cells was up-regulated, suggesting that fatty acids may be important for the formation, maintenance and function of D. vulgaris biofilm. This study offers a valuable perspective on the metabolic dynamics of the D. vulgaris biofilm. PMID: 27299565 [PubMed - as supplied by publisher]

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