PubMed

Related Articles Certified Reference Material for Use in (1)H, (31)P, and (19)F Quantitative NMR, Ensuring Traceability to the International System of Units. J AOAC Int. 2017 Jul 18;: Authors: Rigger R, Rück A, Hellriegel C, Sauermoser R, Morf F, Breitruck K, Obkircher M Abstract In recent years, quantitative NMR (qNMR) spectroscopy has become one of the most important tools for content determination of organic substances and quantitative evaluation of impurities. Using Certified Reference Materials (CRMs) as internal or external standards, the extensively used qNMR method can be applied for purity determination, including unbroken traceability to the International System of Units (SI). The implementation of qNMR toward new application fields, e.g., metabolomics, environmental analysis, and physiological pathway studies, brings along more complex molecules and systems, thus making use of (1)H qNMR challenging. A smart workaround is possible by the use of other NMR active nuclei, namely (31)P and (19)F. This article presents the development of three classes of qNMR CRMs based on different NMR active nuclei ((1)H, (31)P, and (19)F), and the corresponding approaches to establish traceability to the SI through primary CRMs from the National Institute of Standards and Technology and the National Metrology Institute of Japan. These <italic>Trace</italic>CERT(&#x00AE;) qNMR CRMs are produced under ISO/IEC 17025 and ISO Guide 34 using high-performance qNMR. PMID: 28718399 [PubMed - as supplied by publisher]

Related Articles Optimization of lipid extraction and analytical protocols for UHPLC-ESI-HRMS-based lipidomic analysis of adherent mammalian cancer cells. Anal Bioanal Chem. 2017 Jul 17;: Authors: Zhang H, Gao Y, Sun J, Fan S, Yao X, Ran X, Zheng C, Huang M, Bi H Abstract Lipidomics, which reveals comprehensive characterization of molecular lipids, is a rapidly growing technology used in biomedical research. Lipid extraction is a critical step in lipidomic analysis. However, the effectiveness of different lipid extract solvent systems from cellular samples still remains unclear. In the current study, the protocol of reverse-phase liquid chromatography mass spectrometry (LC/MS)-based lipidomics was optimized for extraction and detection of lipids from human pancreatic cancer cell line PANC-1. Four different extraction methods were compared, including methanol/methyl-tert-butyl ether (MTBE)/H2O, methanol/chloroform, methanol/MTBE/chloroform, and hexane/isopropanol. Data were acquired using high-resolution mass spectrometry in positive and negative ion modes respectively. The number of total detected and identified lipids was assessed with the aid of automated lipid identification software LipidSearch. Results demonstrated that methanol/MTBE/H2O provided a better extraction efficiency for different lipid classes, which was chosen as the optimized extraction solvent system. This validated method enables highly sensitive and reproducible analysis for a variety of cellular lipids, which was further applied to an untargeted lipidomic study on human pancreatic cancer PANC-1 cell lines. Moreover, this optimized extraction solvent system can be further applied to other cancer cell lines with similar chemical and physical properties. Graphical abstract Optimized UHPLC-ESI-HRMS-based lipidomic analysis of cancer cells. PMID: 28717896 [PubMed - as supplied by publisher]

Related Articles A novel community driven software for functional enrichment analysis of extracellular vesicles data. J Extracell Vesicles. 2017;6(1):1321455 Authors: Pathan M, Keerthikumar S, Chisanga D, Alessandro R, Ang CS, Askenase P, Batagov AO, Benito-Martin A, Camussi G, Clayton A, Collino F, Di Vizio D, Falcon-Perez JM, Fonseca P, Fonseka P, Fontana S, Gho YS, Hendrix A, Hoen EN, Iraci N, Kastaniegaard K, Kislinger T, Kowal J, Kurochkin IV, Leonardi T, Liang Y, Llorente A, Lunavat TR, Maji S, Monteleone F, Øverbye A, Panaretakis T, Patel T, Peinado H, Pluchino S, Principe S, Ronquist G, Royo F, Sahoo S, Spinelli C, Stensballe A, Théry C, van Herwijnen MJC, Wauben M, Welton JL, Zhao K, Mathivanan S Abstract Bioinformatics tools are imperative for the in depth analysis of heterogeneous high-throughput data. Most of the software tools are developed by specific laboratories or groups or companies wherein they are designed to perform the required analysis for the group. However, such software tools may fail to capture "what the community needs in a tool". Here, we describe a novel community-driven approach to build a comprehensive functional enrichment analysis tool. Using the existing FunRich tool as a template, we invited researchers to request additional features and/or changes. Remarkably, with the enthusiastic participation of the community, we were able to implement 90% of the requested features. FunRich enables plugin for extracellular vesicles wherein users can download and analyse data from Vesiclepedia database. By involving researchers early through community needs software development, we believe that comprehensive analysis tools can be developed in various scientific disciplines. PMID: 28717418 [PubMed]

Related Articles Metabolomics of an in vitro liver model containing primary hepatocytes assembling around an endothelial cell network: comparative study on the metabolic stability and the effect of acetaminophen treatment. J Toxicol Sci. 2017;42(4):445-454 Authors: Toyoda Y, Kashikura K, Soga T, Tagawa YI Abstract Recently, a novel culture system consisting of primary hepatocytes structured over a network of endothelial cells on the Engelbreth-Holm-Swarm (EHS) gel has been reported. This in vitro liver model on the EHS gel (IVLEHS) has been shown to maintain the expression of hepatic genes and their functional activity. Moreover, the IVLEHS was more sensitive to xenobiotics than hepatocyte monocultures, suggesting the potential utility of this culture system for compound hepatotoxicity screening. However, the effect of this three-dimensional structure formation on the cellular metabolic profile of hepatocytes in the IVLEHS is not well understood. To address this concern, we performed metabolome analysis using capillary electrophoresis-time of flight mass spectrometry. Between the IVLEHS and mono-cultured hepatocytes on the EHS gel, there was no significant difference in the levels of metabolites of the urea cycle and the tricarboxylic acid cycle, essential amino acids, and adenylate energy charge (AEC) which is an important indicator of cellular energy status. On the other hand, acetaminophen-dependent decrease of the AEC in the IVLEHS was greater than that in the monoculture, suggesting the higher sensitivity of IVLEHS to acetaminophen-induced hepatotoxicity which is caused by metabolic activation of this drug. Further analysis showed that the levels of taurocholate, one of the major conjugated bile acids, were higher in the IVLEHS than in the monoculture. Considering that the construction of the IVLEHS did not seem to disturb the major cellular metabolism, our findings would strengthen the concept that IVLEHS would have beneficial effects on the maintenance of hepatic functions. PMID: 28717103 [PubMed - in process]

Related Articles Plasma 2-hydroxyglutarate and hexanoylcarnitine levels are potential biomarkers for skeletal muscle toxicity in male Fischer 344 rats. J Toxicol Sci. 2017;42(4):385-396 Authors: Obayashi H, Kobayashi N, Nezu Y, Yamoto T, Shirai M, Asai F Abstract To identify new candidate biomarkers for skeletal muscle toxicity, an unbiased metabolomic analysis was performed in rats treated with two distinct myotoxicants, cerivastatin (CER) and tetramethyl-p-phenylenediamine (TMPD). Skeletal muscle toxicity was induced in male Fischer 344 rats by administering CER or TMPD and monitored using established endpoints, such as increased plasma creatine kinase (CK) activity and histopathology, and a metabolomic analysis of skeletal muscle and plasma samples. Plasma CK levels in CER-treated rats were markedly elevated at Day 11; however, those in TMPD-treated rats showed a statistically significant decrease at 24 hr after dosing. Light microscopy revealed that vacuolated or necrotic fibers were evident in all CER-treated rats on Day 11, and slightly vacuolated fibers were observed in TMPD-treated rats at 6 and 24 hr after dosing. Metabolomic analysis of the rectus femoris indicated increases in 2-hydroxyglutarate (2HG) in CER-treated rats and hexanoylcarnitine in CER- and TMPD-treated rats. There were also increases in plasma 2HG in CER-treated rats on Days 8 and 11 and in TMPD-treated rats at 24 hr after dosing and increases in plasma hexanoylcarnitine in CER-treated rats on Day 11 and in TMPD-treated rats at 6 and 24 hr after dosing. These experiments demonstrated the potential of plasma 2HG and hexanoylcarnitine as specific and easily detectable biomarkers for skeletal muscle toxicity in rats and demonstrated the value of metabolomics for biomarker detection and identification in toxicological studies. PMID: 28717097 [PubMed - in process]

Related Articles Investigating mixotrophic metabolism in the model diatom Phaeodactylum tricornutum. Philos Trans R Soc Lond B Biol Sci. 2017 Sep 05;372(1728): Authors: Villanova V, Fortunato AE, Singh D, Bo DD, Conte M, Obata T, Jouhet J, Fernie AR, Marechal E, Falciatore A, Pagliardini J, Le Monnier A, Poolman M, Curien G, Petroutsos D, Finazzi G Abstract Diatoms are prominent marine microalgae, interesting not only from an ecological point of view, but also for their possible use in biotechnology applications. They can be cultivated in phototrophic conditions, using sunlight as the sole energy source. Some diatoms, however, can also grow in a mixotrophic mode, wherein both light and external reduced carbon contribute to biomass accumulation. In this study, we investigated the consequences of mixotrophy on the growth and metabolism of the pennate diatom Phaeodactylum tricornutum, using glycerol as the source of reduced carbon. Transcriptomics, metabolomics, metabolic modelling and physiological data combine to indicate that glycerol affects the central-carbon, carbon-storage and lipid metabolism of the diatom. In particular, provision of glycerol mimics typical responses of nitrogen limitation on lipid metabolism at the level of triacylglycerol accumulation and fatty acid composition. The presence of glycerol, despite provoking features reminiscent of nutrient limitation, neither diminishes photosynthetic activity nor cell growth, revealing essential aspects of the metabolic flexibility of these microalgae and suggesting possible biotechnological applications of mixotrophy.This article is part of the themed issue 'The peculiar carbon metabolism in diatoms'. PMID: 28717014 [PubMed - in process]

Related Articles Effects of breviscapine on amyloid beta 1-42 induced Alzheimer's disease mice: A HPLC-QTOF-MS based plasma metabonomics study. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jul 01;1057:92-100 Authors: Xia H, Wu L, Chu M, Feng H, Lu C, Wang Q, He M, Ge X Abstract Herba Erigerontis has long been used to cure apoplexy hemiplegia and precordial pain in China. In addition, the bioactivities of its total flavonoids-breviscapine included inhibiting amyloid beta (Aβ) fibril formation, antioxidation and metal chelating, which are beneficial to treat Alzheimer's disease (AD). Hence, A HPLC-QTOF-MS based plasma metabonomics approach was applied to investigate the neuroprotective effects of breviscapine on intracerebroventricular injection of aggregated Aβ 1-42 induced AD mice for the first time in the study. Ten potential biomarkers were screened out by multivariate statistical analysis, eight of which were further identified as indoleacrylic acid, C16 sphinganine, LPE (22:6), sulfolithocholic acid, LPC (16:0), PA (22:1/0:0), taurodeoxycholic acid, and PC (0:0/18:0). According to their metabolic pathways, it was supposed that breviscapine ameliorated the learning and memory deficits of AD mice predominantly by regulating phospholipids metabolism, elevating serotonin level and lowering cholesterols content in vivo. PMID: 28511119 [PubMed - indexed for MEDLINE]

Related Articles Simultaneous determination of selective serotonin reuptake inhibitors and their main metabolites in human breast milk by liquid chromatography-electrospray mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jul 01;1057:101-109 Authors: Weisskopf E, Panchaud A, Nguyen KA, Grosjean D, Hascoët JM, Csajka C, Eap CB, Ansermot N, collaborators of the SSRI-Breast Milk study Abstract A bioanalytical method by high performance liquid chromatography coupled to electrospray mass spectrometry (HPLC-ESI-MS), adapted from a previously published method in plasma, was validated in breast milk for the simultaneous quantification of all antidepressants belonging to the class of selective serotonin reuptake inhibitors (citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline) and their major metabolites (desmethylcitalopram and norfluoxetine). Milk samples (250μl) first underwent protein precipitation followed by solid-phase extraction on a reversed phase/cation exchange sorbent. Analytes were thereafter separated on a XBridge C18 column (2.1mm×100mm; 3.5μm) using a mobile phase composed of ammonium acetate buffer (pH 8.1; 50mM) and acetonitrile in gradient mode. Detection was performed by a single quadrupole mass spectrometer running in selected ion monitoring in positive ionization mode. Method validation covered a wide concentration range of 2-500ng/ml for citalopram, desmethylcitalopram and paroxetine, 5-500ng/ml for sertraline, and 2-1000ng/ml for fluoxetine, norfluoxetine and fluvoxamine. Validation performances such as trueness (90.3-111.6%), repeatability (0.8-9.3%) and intermediate precision (0.9-9.5%) were in agreement with criteria from international guidelines and matrix effects for the analyte/internal standard ratios ranged from 92% to 110% (relative standard deviation <15%). Accuracy profiles (total error of trueness and precision) were lying within the limits of ±30% accepted in bioanalysis. Finally, the method was successfully applied to patient samples collected in a clinical pharmacokinetic study of nursing mothers taking an antidepressant treatment. PMID: 28511118 [PubMed - indexed for MEDLINE]

Related Articles Development of an analysis method for determination of sulfonamides and their five acetylated metabolites in baby foods by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (Orbitrap-MS). J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jul 01;1057:81-91 Authors: Konak ÜI, Certel M, Şık B, Tongur T Abstract A high sensitive and reliable multiresidue method was developed and validated for determination of twelve sulfonamides and five acetylated metabolites in baby foods by using UHPLC-Orbitrap-MS. The sample preparation included two extraction methods as QuEChERS and ASE. The original QuEChERS method was performed, whereas ASE method was optimized to achieve the best recovery for all analytes. UHPLC-Orbitrap-MS parameters were optimized to obtain good retention and separation in LC and high sensitivity and selectivity in MS. The performance of the method was evaluated according to the European Commision Decision 2002/657/EC. Matrix matched calibration curves showed good r(2) (≥0.999) and LOQ was ranged from 0.10 to 0.55μg/kg. ASE was significantly more effective for extraction of the analytes (recovery ranged from 75.5 to 96.6% with RSD≤10.1%) than QuEChERS (recovery ranged from 60.9 to 85.9% with RSD≤19.1%). This method was applied to the analysis of 47 different baby foods and no positive samples were found. PMID: 28505493 [PubMed - indexed for MEDLINE]

Related Articles FluxFix: automatic isotopologue normalization for metabolic tracer analysis. BMC Bioinformatics. 2016 Nov 25;17(1):485 Authors: Trefely S, Ashwell P, Snyder NW Abstract BACKGROUND: Isotopic tracer analysis by mass spectrometry is a core technique for the study of metabolism. Isotopically labeled atoms from substrates, such as [(13)C]-labeled glucose, can be traced by their incorporation over time into specific metabolic products. Mass spectrometry is often used for the detection and differentiation of the isotopologues of each metabolite of interest. For meaningful interpretation, mass spectrometry data from metabolic tracer experiments must be corrected to account for the naturally occurring isotopologue distribution. The calculations required for this correction are time consuming and error prone and existing programs are often platform specific, non-intuitive, commercially licensed and/or limited in accuracy by using theoretical isotopologue distributions, which are prone to artifacts from noise or unresolved interfering signals. RESULTS: Here we present FluxFix ( http://fluxfix.science ), an application freely available on the internet that quickly and reliably transforms signal intensity values into percent mole enrichment for each isotopologue measured. 'Unlabeled' data, representing the measured natural isotopologue distribution for a chosen analyte, is entered by the user. This data is used to generate a correction matrix according to a well-established algorithm. The correction matrix is applied to labeled data, also entered by the user, thus generating the corrected output data. FluxFix is compatible with direct copy and paste from spreadsheet applications including Excel (Microsoft) and Google sheets and automatically adjusts to account for input data dimensions. The program is simple, easy to use, agnostic to the mass spectrometry platform, generalizable to known or unknown metabolites, and can take input data from either a theoretical natural isotopologue distribution or an experimentally measured one. CONCLUSIONS: Our freely available web-based calculator, FluxFix ( http://fluxfix.science ), quickly and reliably corrects metabolic tracer data for natural isotopologue abundance enabling faster, more robust and easily accessible data analysis. PMID: 27887574 [PubMed - indexed for MEDLINE]

Related Articles Exploiting plug-and-play electrochemistry for drug discovery. Future Med Chem. 2016 Apr;8(5):567-77 Authors: Gao L, Teng Y Abstract Electrochemistry has emerged as a powerful analytical technique for chemical analysis of living cells, biologically active molecules and metabolites. Electrochemical biosensor, microfluidics and mass spectrometry are the most frequently used methods for electrochemical detection and monitory, which comprise a collection of extremely useful measurement tools for various fields of biology and medicine. Most recently, electrochemistry has been shown to be coupled with nanotechnology and genetic engineering to generate new enabling technologies, providing rapid, selective, and sensitive detection and diagnosis platforms. The primary focus of this review is to highlight the utility of electrochemical strategies and their conjunction with other approaches for drug metabolism and discovery. Current challenges and possible future developments and applications of electrochemistry in drug studies are also discussed. PMID: 27079543 [PubMed - indexed for MEDLINE]

18 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 2017/07/18PubMed comprises more than millions of 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.

Grapevine tissues and phenology differentially affect soluble carbohydrates determination by capillary electrophoresis. Plant Physiol Biochem. 2017 Jul 08;118:394-399 Authors: Moreno D, Berli F, Bottini R, Piccoli PN, Silva MF Abstract Soluble carbohydrates distribution depends on plant physiology and, among other important factors, determines fruit yield and quality. In plant biology, the analysis of sugars is useful for many purposes, including metabolic studies. Capillary electrophoresis (CE) proved to be a powerful green separation technique with minimal sample preparation, even in complex plant tissues, that can provide high-resolution efficiency. Matrix effect refers to alterations in the analytical response caused by components of a sample other than the analyte of interest. Thus, the assessment and reduction of the matrix factor is fundamental for metabolic studies in different matrices. The present study evaluated the source and levels of matrix effects in the determination of most abundant sugars in grapevine tissues (mature and young leaves, berries and roots) at two phenological growth stages. Sucrose was the sugar that showed the least matrix effects, while fructose was the most affected analyte. Based on plant tissues, young leaves presented the smaller matrix effects, irrespectively of the phenology. These changes may be attributed to considerable differences at chemical composition of grapevine tissues with plant development. Therefore, matrix effect should be an important concern for plant metabolomics. PMID: 28711788 [PubMed - as supplied by publisher]

The human microbiome. Adv Med Sci. 2017 Jul 13;62(2):414-420 Authors: Blum HE Abstract Until recently, human microbiology was based on the identification of single microbes, such as bacteria, fungi and viruses, frequently isolated from patients with acute or chronic infections. Novel culture-independent molecular biochemical analyses (genomics, transcriptomics, proteomics, metabolomics) allow today to detect and classify the diverse microorganisms in a given ecosystem (microbiota), such as the gastrointestinal tract, the skin, the airway system, the urogenital tract and others, and to assess all genomes in these ecosystems (microbiome) as well as their gene products. These analyses revealed that each individual has its own microbiota that plays a role in health and disease. In addition, they greatly contributed to the recent advances in the understanding of the pathogenesis of a wide range of human diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine. PMID: 28711782 [PubMed - as supplied by publisher]

Metabolomic profiling reveals potential biomarkers in esophageal cancer progression using liquid chromatography-mass spectrometry platform. Biochem Biophys Res Commun. 2017 Jul 12;: Authors: Zhang H, Wang L, Hou Z, Ma H, Mamtimin B, Hasim A, Sheyhidin I Abstract Esophageal cancer (EC) is one of the most common malignancies with poor prognosis. Metabolomics has been shown to be a powerful approach to discover the potential biomarkers for cancer diagnosis and prognosis. The goal of this study is to screen potential biomarkers for early diagnosis and prognosis. In this study, 40 tissue samples and the corresponding control samples from the same esophageal squamous cell carcinoma (ESCC) patients were analyzed by liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. 20 potential diagnostic biomarkers were selected. Moreover, 9 metabolites were found to be closely correlated with the pathological feature such as local invasion, lymphatic metastasis and postoperative survival time. Glutamate was correlated with local invasion of tumor, and oleic acid, LysoPC(15:0), uracil, inosine and choline were closely related with the lymphatic metastasis, while glutamine, kynurenine, serine and uracil were related with postoperative survival time. The results indicated that the potential biomarkers discovered by metabolomics could reflect the metabolic characterization of ESCC, and offers a novel approach for early diagnosis, assessment and prognosis of the disease. PMID: 28711496 [PubMed - as supplied by publisher]

Ligustrazine modulates renal cysteine biosynthesis in rats exposed to cadmium. Environ Toxicol Pharmacol. 2017 Jul 09;54:125-132 Authors: Kuang W, Zhang X, Zhu W, Lan Z Abstract The objective of this study was to determine the effect of ligustrazine (TMP) on cadmium (Cd)-induced nephrotoxicity and its relevant mechanism. TMP (50mg/kg) was injected intraperitoneally (i.p.) into rats 1h prior to CdCl2 exposure (at a Cd dose of 0.6mg/kg). TMP reversed Cd-induced nephrotoxicity, evidenced by the relatively normal architecture of the renal cortex. Additionally, TMP alleviated renal oxidative stress of rats that were exposed to Cd, evidenced by the decreased levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), elevated levels of glutathione (GSH) and GSH/GSSG (glutathione disulfide) ratios. Furthermore, TMP also raised the decreased levels of S-adenosylmethionine (SAM) and cystathionine involved in cysteine biosynthesis in rats exposed to Cd. Further analysis revealed that TMP treatment upregulated expression of several proteins involved in cysteine biosynthesis including methionine adenosyltransferases (MATs) and cystathionine-beta-synthase (CBS). Taken together, these results suggest that TMP remodeled metabolomics of cysteine biosynthesis in rat kidneys and attenuated Cd-induced nephrotoxicity. PMID: 28710931 [PubMed - as supplied by publisher]

ROS Mediated Selection for Increased NADPH Availability in Escherichia coli. Biotechnol Bioeng. 2017 Jul 15;: Authors: Steele Reynolds T, Courtney CM, Erickson KE, Wolfe LM, Chatterjee A, Nagpal P, Gill RT Abstract The economical production of chemicals and fuels by microbial processes remains an intense area of interest in biotechnology. A key limitation in such efforts concerns the availability of key co-factors, in this case NADPH, required for target pathways. Many of the strategies pursued for increasing NADPH availability in Escherichia coli involve manipulations to the central metabolism, which can create redox imbalances and overall growth defects. In this study we used a reactive oxygen species based selection to search for novel methods of increasing NADPH availability. We report a loss of function mutation in the gene hdfR appears to increase NADPH availability in E. coli. Additionally, we show this excess NADPH can be used to improve the production of 3HP in E. coli. This article is protected by copyright. All rights reserved. PMID: 28710857 [PubMed - as supplied by publisher]

Opportunities and Challenges for Environmental Exposure Assessment in Population-Based Studies. Cancer Epidemiol Biomarkers Prev. 2017 Jul 14;: Authors: Patel CJ, Kerr J, Thomas DC, Mukherjee B, Ritz B, Chatterjee N, Jankowska MM, Madan J, Karagas MR, McAllister KA, Mechanic LE, Fallin MD, Ladd-Acosta C, Blair IA, Teiltelbaum SL, Amos CI Abstract BACKGROUND: A growing number and increasing diversity of factors are available for epidemiological studies. These measures provide new avenues for discovery and prevention yet they also raise many challenges for adoption in epidemiological investigations. METHODS: We evaluate 1) designs to investigate diseases that consider heterogeneous and multi-dimensional indicators of exposure and behavior, 2) the implementation of numerous methods to capture indicators of exposure, and 3) the analytical methods required for discovery and validation. RESULTS: Case-control studies have provided insights into genetic susceptibility but are insufficient for characterizing complex effects of environmental factors on disease development. Prospective designs are required but must balance extended data collection with follow-up of study participants. Two phase designs are described. We discuss innovations in assessments including the microbiome, mass spectrometry and metabolomics, behavioral assessment, dietary, physical activity and occupational exposure assessment, air pollution monitoring and global positioning and individual sensors. The availability of extensive correlated data raises new challenges in disentangling specific exposures that influence cancer risk from among extensive and often correlated exposures. CONCLUSIONS: New exposure assessments offer many new opportunities for environmental assessment in cancer development. IMPACT: We describe and evaluate the state of the art for evaluating high dimensional environmental studies. PMID: 28710076 [PubMed - as supplied by publisher]

Circulating Acylcarnitine Profile in Human Heart Failure: A Surrogate of Fatty Acid Metabolic Dysregulation in Mitochondria and Beyond. Am J Physiol Heart Circ Physiol. 2017 Jul 14;:ajpheart.00820.2016 Authors: Ruiz M, Labarthe F, Fortier A, Bouchard B, Thompson Legault J, Bolduc V, Rigal O, Chen J, Ducharme A, Crawford PA, Tardif JC, Des Rosiers C Abstract Heart failure (HF) is associated with metabolic perturbations, particularly of fatty acids (FA), which remain to be better understood in humans. This study aimed at testing the hypothesis that HF patients with reduced ejection fraction, display systemic perturbations in levels of energy-related metabolites, especially those reflecting dysregulation of FA metabolism, namely acylcarnitines (ACs). Circulating metabolites were assessed using mass spectrometry (MS)-based methods in two cohorts. The main cohort consisted of 72 controls and 68 HF patients, exhibiting depressed left ventricular ejection fraction (25.9±6.9%) and mostly of ischemic etiology with ≥ 2 comorbidities. HF patients displayed marginal changes in plasma levels of Krebs cycle-related metabolites or indices of mitochondrial or cytosolic redox status. They had, however, 22-79% higher circulating ACs, irrespective of chain length (p<0.0001; adjusted for sex, age, renal function and insulin resistance; determined by tandem MS), which reflect defective mitochondrial β-oxidation and were significantly associated with levels of NT-Pro-BNP levels, a disease severity marker. Subsequent extended LC-MS/MS analysis of 53 plasma ACs in a subset group from the primary cohort, confirmed and further substantiated with a comprehensive lipidomic analysis in a validation cohort, revealed in HF patients a more complex circulating AC profile. The latter included dicarboxylic-ACs and dihydroxy-ACs as well as AC or sphingolipids with very-long chain (VLC)-FAs (>20 carbons), which are proxies of dysregulated FA metabolism in peroxisomes. Our study identified alterations in circulating ACs in HF patients, which are independent of biological traits and associated with disease severity markers. These alterations reflect dysfunctional FA metabolism in mitochondria, but also beyond, namely in peroxisomes, suggesting a novel mechanism contributing to global lipid perturbations in human HF. PMID: 28710072 [PubMed - as supplied by publisher]

Create, run, share, publish, and reference your LC-MS, FIA-MS, GC-MS, and NMR data analysis workflows with Workflow4Metabolomics 3.0, the Galaxy online infrastructure for metabolomics. Int J Biochem Cell Biol. 2017 Jul 11;: Authors: Guitton Y, Tremblay-Franco M, Le Corguillé G, Martin JF, Pétéra M, Roger-Mele P, Delabrière A, Goulitquer S, Monsoor M, Duperier C, Canlet C, Servien R, Tardivel P, Caron C, Giacomoni F, Thévenot EA Abstract Metabolomics is a key approach in modern functional genomics and systems biology. Due to the complexity of metabolomics data, the variety of experimental designs, and the variety of existing bioinformatics tools, providing experimenters with a simple and efficient resource to conduct comprehensive and rigorous analysis of their data is of utmost importance. In 2014, we launched the Workflow4Metabolomics (W4M; http://workflow4metabolomics.org) online infrastructure for metabolomics built on the Galaxy environment, which offers user-friendly features to build and run data analysis workflows including preprocessing, statistical analysis, and annotation steps. Here we present the new W4M 3.0 release, which contains twice as many tools as the first version, and provides two features which are, to our knowledge, unique among online resources. First, data from the four major metabolomics technologies (i.e., LC-MS, FIA-MS, GC-MS, and NMR) can be analyzed on a single platform. By using three studies in human physiology, alga evolution, and animal toxicology, we demonstrate how the 40 available tools can be easily combined to address biological issues. Second, the full analysis (including the workflow, the parameter values, the input data and output results) can be referenced with a permanent digital object identifier (DOI). Publication of data analyses is of major importance for robust and reproducible science. Furthermore, the publicly shared workflows are of high-value for e-learning and training. The Workflow4Metabolomics 3.0 e-infrastructure thus not only offers a unique online environment for analysis of data from the main metabolomics technologies, but it is also the first reference repository for metabolomics workflows. PMID: 28710041 [PubMed - as supplied by publisher]