PubMed

Related Articles The disorder metabolic profiling in kidney and spleen of mice induced by mycotoxins deoxynivalenol through gas chromatography mass spectrometry. Chemosphere. 2017 Mar 31;180:267-274 Authors: Ji J, Zhu P, Cui F, Pi F, Zhang Y, Sun X Abstract Gas chromatography mass spectrometry (GC-MS) based metabolomics strategy was implemented for the metabolites detection in kidney and spleen samples of mice, which were treated with 2 mg kg(-1) deoxynivalenol (DON), through intragastric administration for three weeks, for studying the toxicity of DON on the metabolic profiling in kidney and spleen. The spectrum was deconvoluted, aligned and identified with MS DIAL, equipped with Fiehn library. And the data matrix was processed with univariate analysis and multivariate analysis for selection of metabolites with VIP >1, t-test p value < 0.05. The metabolic pathway analysis was analyzed with MetaMapp and drew by CytoScape. Result shows that DON could induce an increased protein synthesis to repair the damaged membrane protein structure, in both kidney and spleen, with decrease of valine, leucine and phenylalanine, et al. essential precursors for protein synthesis and energy production; the energy metabolism in kidney disordered by DON, with the decreasing of ribitol, glycerol 1-phosphate, et al. Furthermore, DON could lead to the disorder in immunity function and nucleotide metabolism in spleen, with decreasing trend of cytidine and alanine. PMID: 28411543 [PubMed - as supplied by publisher]

Related Articles A Comprehensive Analysis of Myocardial Substrate Preference Emphasizes the Need For a Synchronized Fluxomic/Metabolomic Research Design. Am J Physiol Heart Circ Physiol. 2017 Apr 14;:ajpheart.00016.2017 Authors: Ragavan M, Kirpich A, Fu X, Burgess SC, McIntyre LM, Merritt ME Abstract The heart oxidizes fatty acids, carbohydrates and ketone bodies inside the citric acid cycle (CAC) to generate the reducing equivalents needed for ATP production. Competition between these substrates makes it difficult to estimate the extent of pyruvate oxidation. Previously, hyperpolarized pyruvate detected propionate mediated activation of carbohydrate oxidation, even in the presence of acetate. In this report, the optimal concentration of propionate for activation of glucose oxidation is measured in mouse hearts perfused in Langendorff mode. This study was performed with a more physiologically relevant perfusate than the previous work. Increasing concentrations of propionate did not cause adverse effects on myocardial metabolism, as evidenced by unchanged O2 consumption,citric acid cycle (CAC) flux, and developed pressures. One mM propionate was sufficient to achieve significant increases in PDH flux (3x) and anaplerosis (6x) as measured by isotopomer analysis. These results further demonstrate the potential of propionate as an aid for the correct estimation of total carbohydrate oxidative capacity in the heart. However, LC/MS based metabolomics detected large changes (~ 30 fold) in malate and fumarate pool sizes. This observation leads to a key observation regarding mass balance in the CAC: flux through a portion of the cycle can be drastically elevated without changing the O2 consumption. PMID: 28411229 [PubMed - as supplied by publisher]

Related Articles Mass spectrometry imaging shows major derangements in neurogranin and in purine metabolism in the triple-knockout 3×Tg Alzheimer mouse model. Biochim Biophys Acta. 2017 Apr 11;: Authors: Esteve C, Jones EA, Kell DB, Boutin H, McDonnell LA Abstract Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) can simultaneously measure hundreds of biomolecules directly from tissue. Using different sample preparation strategies, proteins and metabolites have been profiled to study the molecular changes in a 3×Tg mouse model of Alzheimer's disease. In comparison with wild-type (WT) control mice MALDI-MSI revealed Alzheimer's disease-specific protein profiles, highlighting dramatic reductions of a protein with m/z 7560, which was assigned to neurogranin and validated by immunohistochemistry. The analysis also revealed substantial metabolite changes, especially in metabolites related to the purine metabolic pathway, with a shift towards an increase in hypoxanthine/xanthine/uric acid in the 3×Tg AD mice accompanied by a decrease in AMP and adenine. Interestingly these changes were also associated with a decrease in ascorbic acid, consistent with oxidative stress. Furthermore, the metabolite N-arachidonyl taurine was increased in the diseased mouse brain sections, being highly abundant in the hippocampus. Overall, we describe an interesting shift towards pro-inflammatory molecules (uric acid) in the purinergic pathway associated with a decrease in anti-oxidant level (ascorbic acid). Together, these observations fit well with the increased oxidative stress and neuroinflammation commonly observed in AD. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. PMID: 28411106 [PubMed - as supplied by publisher]

Multi-omics and male infertility: status, integration and future prospects. Front Biosci (Schol Ed). 2017 Jun 01;9:375-394 Authors: Sinha A, Singh V, Yadav S Abstract Within the cell, gene expression analysis is the key to gain information about  different cellular and physiological events. The multifaceted route of fertilization is a combination of different processes, which include production, maturation and ejaculation of the sperm, its travel through the female genital tract, followed by the ultimate fusion of the fertile sperm with the egg. Early embryogenesis and gametogenesis as well as gene expression at tissue level and global gene silencing are under different levels of stringent epigenetic checks. Moreover, transcriptome (expressed segment of the genome in form of RNA) and the proteome (expressed set of genomic proteins) contribute uniformly to the overall cellular gene expression. In both normal and pathophysiological environments, this gene expression is altered across various levels viz., genome variations, post-transcriptional modifications, protein expression and post translational modifications. Consequently, more informative conclusions can be drawn through a new 'omics' approach of system biology, which takes into account all the genomics, epigenomics, proteomics, and metabolomics findings under one roof, thus computing the alterations in all the entities (genes, proteins, metabolites) concurrently. PMID: 28410125 [PubMed - in process]

Related Articles Clinical and Laboratory Diagnosis of Peroxisomal Disorders. Methods Mol Biol. 2017;1595:329-342 Authors: Wanders RJ, Klouwer FC, Ferdinandusse S, Waterham HR, Poll-Thé BT Abstract The peroxisomal disorders (PDs) are a heterogeneous group of genetic diseases in man caused by an impairment in peroxisome biogenesis or one of the metabolic functions of peroxisomes. Thanks to the revolutionary technical developments in gene sequencing methods and their increased use in patient diagnosis, the field of genetic diseases in general and peroxisomal disorders in particular has dramatically changed in the last few years. Indeed, several novel peroxisomal disorders have been identified recently and in addition it has been realized that the phenotypic spectrum of patients affected by a PD keeps widening, which makes clinical recognition of peroxisomal patients increasingly difficult. Here, we describe these new developments and provide guidelines for the clinical and laboratory diagnosis of peroxisomal patients. PMID: 28409475 [PubMed - in process]

Related Articles An integrative overview of the molecular and physiological responses of sugarcane under drought conditions. Plant Mol Biol. 2017 Apr 13;: Authors: Vital CE, Giordano A, de Almeida Soares E, Rhys Williams TC, Mesquita RO, Vidigal PM, de Santana Lopes A, Pacheco TG, Rogalski M, de Oliveira Ramos HJ, Loureiro ME Abstract Drought is the main abiotic stress constraining sugarcane production. However, our limited understanding of the molecular mechanisms involved in the drought stress responses of sugarcane impairs the development of new technologies to increase sugarcane drought tolerance. Here, an integrated approach was performed to reveal the molecular and physiological changes in two closely related sugarcane cultivars, including the most extensively planted cultivar in Brazil (cv. RB867515), in response to moderate (-0.5 MPa) and severe (-1 MPa) drought stress at the transcriptional, translational, and posttranslational levels. The results show common and cultivar exclusive changes in specific genes related to photosynthesis, carbohydrate, amino acid, and phytohormone metabolism. The novel phosphoproteomics and redox proteomic analysis revealed the importance of posttranslational regulation mechanisms during sugarcane drought stress. The shift to soluble sugar, secondary metabolite production, and activation of ROS eliminating processes in response to drought tolerance were mechanisms exclusive to cv. RB867515, helping to explain the better performance and higher production of this cultivar under these stress conditions. PMID: 28409321 [PubMed - as supplied by publisher]

Related Articles Plasma sphingolipids in HIV-associated chronic obstructive pulmonary disease. BMJ Open Respir Res. 2017;4(1):e000180 Authors: Hodgson S, Griffin TJ, Reilly C, Harvey S, Witthuhn BA, Sandri BJ, Kunisaki KM, Wendt CH Abstract INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity in persons living with HIV (PLWH) and HIV appears to uniquely cause COPD, independent of smoking. The mechanisms by which HIV leads to COPD are not clear. The objective of this study was to identify metabolomic biomarkers and potential mechanistic pathways of HIV-associated COPD (HIV-COPD). METHODS: We performed case-control metabolite profiling via mass spectrometry in plasma from 38 individuals with HIV-COPD (cases), comparing to matched controls with/without HIV and with/without COPD. Untargeted metabolites of interest were identified with liquid chromatography with mass spectrometry (LC-MS/mass spectrometry (MS)), and targeted metabolomics for tryptophan (Trp) and kynurenine (Kyn) were measured by selective reaction monitoring (SRM) with LC-MS/MS. We used mixed-effects models to compare metabolite concentrations in cases compared with controls while controlling for relevant biological variables. RESULTS: We identified 1689 analytes associated with HIV-COPD at a false discovery rate (FDR) of 10%. In PLWH, we identified 263 analytes (10% FDR) between those with and without COPD. LC MS/MS identified Trp and 17 lipids, including sphingolipids and diacylglycerol. After adjusting for relevant covariates, the Kyn/Trp ratio measured by SRM was significantly higher in PLWH (p=0.022), but was not associated with COPD status (p=0.95). CONCLUSIONS: There is a unique metabolite profile in HIV-COPD that includes sphingolipids. Trp metabolism is increased in HIV, but does not appear to independently contribute to HIV-COPD. TRIAL REGISTRATION NUMBERS: NCT01810289, NCT01797367, NCT00608764. PMID: 28409005 [PubMed]

Related Articles A Bayesian Model for the Prediction and Early Diagnosis of Alzheimer's Disease. Front Aging Neurosci. 2017;9:77 Authors: Alexiou A, Mantzavinos VD, Greig NH, Kamal MA Abstract Alzheimer's disease treatment is still an open problem. The diversity of symptoms, the alterations in common pathophysiology, the existence of asymptomatic cases, the different types of sporadic and familial Alzheimer's and their relevance with other types of dementia and comorbidities, have already created a myth-fear against the leading disease of the twenty first century. Many failed latest clinical trials and novel medications have revealed the early diagnosis as the most critical treatment solution, even though scientists tested the amyloid hypothesis and few related drugs. Unfortunately, latest studies have indicated that the disease begins at the very young ages thus making it difficult to determine the right time of proper treatment. By taking into consideration all these multivariate aspects and unreliable factors against an appropriate treatment, we focused our research on a non-classic statistical evaluation of the most known and accepted Alzheimer's biomarkers. Therefore, in this paper, the code and few experimental results of a computational Bayesian tool have being reported, dedicated to the correlation and assessment of several Alzheimer's biomarkers to export a probabilistic medical prognostic process. This new statistical software is executable in the Bayesian software Winbugs, based on the latest Alzheimer's classification and the formulation of the known relative probabilities of the various biomarkers, correlated with Alzheimer's progression, through a set of discrete distributions. A user-friendly web page has been implemented for the supporting of medical doctors and researchers, to upload Alzheimer's tests and receive statistics on the occurrence of Alzheimer's disease development or presence, due to abnormal testing in one or more biomarkers. PMID: 28408880 [PubMed - in process]

Related Articles Multiomics of tomato glandular trichomes reveals distinct features of central carbon metabolism supporting high productivity of specialized metabolites. Plant Cell. 2017 Apr 13;: Authors: Balcke G, Bennewitz S, Bergau N, Athmer B, Henning A, Majovsky P, Jiménez-Gómez JM, Hoehenwarter W, Tissier AF Abstract Glandular trichomes are metabolic cell factories with the capacity to produce large quantities of secondary metabolites. Little is known about the connection between central carbon metabolism and metabolic productivity for secondary metabolites in glandular trichomes. To address this gap in our knowledge, we performed comparative metabolomics, transcriptomics, proteomics and 13C-labeling of type VI glandular trichomes and leaves from a cultivated (Solanum lycopersicum LA4024) and a wild (Solanum habrochaites LA1777) tomato accession. Specific features of glandular trichomes that drive the formation of secondary metabolites could be identified. Tomato type VI trichomes are photosynthetic but acquire their carbon essentially from leaf sucrose. The energy and reducing power from photosynthesis are used to support the biosynthesis of secondary metabolites, while the comparatively reduced Calvin-Benson-Bassham cycle activity may be involved in recycling metabolic CO2. Glandular trichomes cope with oxidative stress by producing high levels of polyunsaturated fatty acids, oxylipins, and glutathione. Finally, distinct mechanisms are present in glandular trichomes to increase the supply of precursors for the isoprenoid pathways. Particularly, the citrate-malate shuttle supplies cytosolic acetyl CoA and plastidic glycolysis and malic enzyme support the formation of plastidic pyruvate. A model is proposed on how glandular trichomes achieve high metabolic productivity. PMID: 28408661 [PubMed - as supplied by publisher]

Related Articles Gastroparesis and lipid metabolism-associated dysbiosis in Wistar Kyoto rats. Am J Physiol Gastrointest Liver Physiol. 2017 Apr 13;:ajpgi.00008.2017 Authors: Dalziel JE, Fraser K, Young W, Lloyd-West CM, Bassett SA, Roy NC Abstract Altered gastric accommodation and intestinal morphology suggests impaired gastrointestinal (GI) transit may occur in the Wistar Kyoto (WKY) rat strain, as common in stress-associated functional GI disorders. Because changes in GI transit can alter microbiota composition, we investigated whether these are altered in WKY rats compared with the resilient Sprague Dawley (SD) rats under basal conditions, and characterized plasma lipid and metabolite differences. Bead transit was tracked by X-ray imaging to monitor: gastric emptying (GE; 4 h), small intestine (SI) transit (9 h) and large intestine transit (12 h). Plasma extracts were analysed by lipid and HILIC LC-MS. Cecal microbial composition was determined by Illumina MiSeq 16S rRNA amplicon sequencing and analysis using the QIIME pipeline. Stomach retention of beads was 77% for WKY compared with 35% for SD rats. GI transit was decreased by 34% (9 h), and 21% (12 h) in WKY compared with SD rats. Excluding stomach retention, transiting beads moved 29% further along the SI over 4-9 h for WKY compared with SD rats. Cecal Ruminococcus, Roseburia, and unclassified Lachnospiraceae genera were less abundant in WKY rats, whereas the minor taxa Dorea, Turicibacter, and Lactobacillus were higher. Diglycerides, triglycerides, phosphatidyl-ethanolamines and phosphatidylserine were lower in WKY rats, whereas cholesterol esters and taurocholic acids were higher. The unexpected WKY rat phenotype of delayed gastric emptying, yet rapid SI transit, was associated with altered lipid and metabolite profiles. The delayed gastric emptying of the WKY phenotype suggests this rat strain may be useful as a model for gastroparesis. PMID: 28408641 [PubMed - as supplied by publisher]

Related Articles Lipidomics in biomedical research-practical considerations. Biochim Biophys Acta. 2017 Apr 10;: Authors: Hyötyläinen T, Ahonen L, Pöhö P, Orešič M Abstract Lipids have many central physiological roles including as structural components of cell membranes, energy storage sources and intermediates in signaling pathways. Lipid-related disturbances are known to underlie many diseases and their co-morbidities. The emergence of lipidomics has empowered researchers to study lipid metabolism at the cellular as well as physiological levels at a greater depth than was previously possible. The key challenges ahead in the field of lipidomics in medical research lie in the development of experimental protocols and in silico techniques needed to study lipidomes at the systems level. Clinical questions where lipidomics may have an impact in healthcare settings also need to be identified, both from the health outcomes and health economics perspectives. This article is part of a Special Issue entitled: BBALIP_Lipidomics Opinion Articles edited by Sepp Kohlwein. PMID: 28408341 [PubMed - as supplied by publisher]

Related Articles Intratumor Heterogeneity in Primary Kidney Cancer Revealed by Metabolic Profiling of Multiple Spatially Separated Samples within Tumors. EBioMedicine. 2017 Apr 06;: Authors: Okegawa T, Morimoto M, Nishizawa S, Kitazawa S, Honda K, Araki H, Tamura T, Ando A, Satomi Y, Nutahara K, Hara T Abstract Metabolic alteration constitutes a hallmark of cancer. Glycolysis and antioxidant pathways in kidney cancer are elevated, with frequent mutation of the VHL gene. Intratumor genetic heterogeneity has been recently demonstrated in kidney cancer. However, intratumor metabolic heterogeneity has not been investigated. Here, we used global metabolomics analysis and tissue slice tracer studies to demonstrate that different portions of a human primary kidney tumor possess different metabolic characteristics and drug sensitivity. Pyruvate levels were elevated and pyruvate metabolism was altered in some tumor sections. These observations indicated that pyruvate metabolism may constitute a possible vulnerability of kidney cancer; indeed, pyruvate stimulated the growth of primary kidney cancer cells and pharmacological inhibition of pyruvate transporters slowed the growth of patient-derived kidney tumors in mice. These findings deepen our understanding of the intratumor metabolic heterogeneity of kidney cancer and may inform novel therapeutic approaches in human kidney cancer. PMID: 28408240 [PubMed - as supplied by publisher]

Related Articles Structural characterization of reaction products of caftaric acid and bisulfite present in a commercial wine using high resolution mass spectrometric and nuclear magnetic resonance techniques. Food Chem. 2017 Sep 01;230:99-107 Authors: Hayasaka Y, Black CA, Hack J, Smith P Abstract Reaction products of bisulfite and caftaric acid were found in wines containing sulfites as a preservative. Acidic compounds were separated from wine and analyzed by HPLC combined with DAD and QTOF mass spectrometer. HPLC chromatograms of the expected [M-H](-) ion and UV absorption revealed the presence of five possible reaction products (a-e). These compounds were isolated then characterized by NMR and confirmed to be the reaction products as follows; 5-sulfo-(E)-caftaric acid (a), 2-sulfo-(Z)-caftaric acid (b), 2-sulfo-(E)-caftaric acid (c), (E)-caftaric acid-4-O-sulfate (d) and (E)-caftaric acid-3-O-sulfate (e). UV spectra and high resolution product ion spectra of the five compounds also supported their identity. The reaction products were confirmed to be commonly present in commercial wines across four vintages and two varieties. Their concentration was found to be as much as that of 2-S-glutathionyl caftaric acid, suggesting that bisulfite consistently competes as a nucleophile with glutathione for the o-quinone of caftaric acid. PMID: 28407977 [PubMed - in process]

Related Articles Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort. Genome Biol. 2017 Apr 13;18(1):70 Authors: Org E, Blum Y, Kasela S, Mehrabian M, Kuusisto J, Kangas AJ, Soininen P, Wang Z, Ala-Korpela M, Hazen SL, Laakso M, Lusis AJ Abstract BACKGROUND: The gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study. RESULTS: We investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota-metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state. CONCLUSIONS: Our study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host-gut microbiota relationships. PMID: 28407784 [PubMed - in process]

Related Articles Omics analysis of acetic acid tolerance in Saccharomyces cerevisiae. World J Microbiol Biotechnol. 2017 May;33(5):94 Authors: Geng P, Zhang L, Shi GY Abstract Acetic acid is an inhibitor in industrial processes such as wine making and bioethanol production from cellulosic hydrolysate. It causes energy depletion, inhibition of metabolic enzyme activity, growth arrest and ethanol productivity losses in Saccharomyces cerevisiae. Therefore, understanding the mechanisms of the yeast responses to acetic acid stress is essential for improving acetic acid tolerance and ethanol production. Although 329 genes associated with acetic acid tolerance have been identified in the Saccharomyces genome and included in the database ( http://www.yeastgenome.org/observable/resistance_to_acetic_acid/overview ), the cellular mechanistic responses to acetic acid remain unclear in this organism. Post-genomic approaches such as transcriptomics, proteomics, metabolomics and chemogenomics are being applied to yeast and are providing insight into the mechanisms and interactions of genes, proteins and other components that together determine complex quantitative phenotypic traits such as acetic acid tolerance. This review focuses on these omics approaches in the response to acetic acid in S. cerevisiae. Additionally, several novel strains with improved acetic acid tolerance have been engineered by modifying key genes, and the application of these strains and recently acquired knowledge to industrial processes is also discussed. PMID: 28405910 [PubMed - in process]

Related Articles LipidFinder: A computational workflow for discovery of lipids identifies eicosanoid-phosphoinositides in platelets. JCI Insight. 2017 Apr 06;2(7):e91634 Authors: O'Connor A, Brasher CJ, Slatter DA, Meckelmann SW, Hawksworth JI, Allen SM, O'Donnell VB Abstract Accurate and high-quality curation of lipidomic datasets generated from plasma, cells, or tissues is becoming essential for cell biology investigations and biomarker discovery for personalized medicine. However, a major challenge lies in removing artifacts otherwise mistakenly interpreted as real lipids from large mass spectrometry files (>60 K features), while retaining genuine ions in the dataset. This requires powerful informatics tools; however, available workflows have not been tailored specifically for lipidomics, particularly discovery research. We designed LipidFinder, an open-source Python workflow. An algorithm is included that optimizes analysis based on users' own data, and outputs are screened against online databases and categorized into LIPID MAPS classes. LipidFinder outperformed three widely used metabolomics packages using data from human platelets. We show a family of three 12-hydroxyeicosatetraenoic acid phosphoinositides (16:0/, 18:1/, 18:0/12-HETE-PI) generated by thrombin-activated platelets, indicating crosstalk between eicosanoid and phosphoinositide pathways in human cells. The software is available on GitHub (https://github.com/cjbrasher/LipidFinder), with full userguides. PMID: 28405621 [PubMed - in process]

Related Articles Prolonged activation of IL-5-producing ILC2 causes pulmonary arterial hypertrophy. JCI Insight. 2017 Apr 06;2(7):e90721 Authors: Ikutani M, Tsuneyama K, Kawaguchi M, Fukuoka J, Kudo F, Nakae S, Arita M, Nagai Y, Takaki S, Takatsu K Abstract IL-33 is one of the critical cytokines that activates group 2 innate lymphoid cells (ILC2s) and mediates allergic reactions. Accumulating evidence suggests that IL-33 is also involved in the pathogenesis of several chronic inflammatory diseases. Previously, we generated an IL-5 reporter mouse and revealed that lung IL-5-producing ILC2s played essential roles in regulating eosinophil biology. In this study, we evaluated the consequences of IL-33 administration over a long period, and we observed significant expansion of ILC2s and eosinophils surrounding pulmonary arteries. Unexpectedly, pulmonary arteries showed severe occlusive hypertrophy that was ameliorated in IL-5- or eosinophil-deficient mice, but not in Rag2-deficient mice. This indicates that IL-5-producing ILC2s and eosinophils play pivotal roles in pulmonary arterial hypertrophy. Administration of a clinically used vasodilator was effective in reducing IL-33-induced hypertrophy and repressed the expansion of ILC2s and eosinophils. Taken together, these observations demonstrate a previously unrecognized mechanism in the development of pulmonary arterial hypertrophy and the causative roles of ILC2 in the process. PMID: 28405615 [PubMed - in process]

Related Articles Calreticulin and type I interferon: An unsuspected connection. Oncoimmunology. 2017;6(3):e1288334 Authors: Galluzzi L, Kroemer G PMID: 28405522 [PubMed - in process]

Related Articles Mass Spectrometry Based Molecular 3D-Cartography of Plant Metabolites. Front Plant Sci. 2017;8:429 Authors: Floros DJ, Petras D, Kapono CA, Melnik AV, Ling TJ, Knight R, Dorrestein PC Abstract Plants play an essential part in global carbon fixing through photosynthesis and are the primary food and energy source for humans. Understanding them thoroughly is therefore of highest interest for humanity. Advances in DNA and RNA sequencing and in protein and metabolite analysis allow the systematic description of plant composition at the molecular level. With imaging mass spectrometry, we can now add a spatial level, typically in the micrometer-to-centimeter range, to their compositions, essential for a detailed molecular understanding. Here we present an LC-MS based approach for 3D plant imaging, which is scalable and allows the analysis of entire plants. We applied this approach in a case study to pepper and tomato plants. Together with MS/MS spectra library matching and spectral networking, this non-targeted workflow provides the highest sensitivity and selectivity for the molecular annotations and imaging of plants, laying the foundation for studies of plant metabolism and plant-environment interactions. PMID: 28405197 [PubMed - in process]

Related Articles Metabolomics uncovers a link between inositol metabolism and osteosarcoma metastasis. Oncotarget. 2017 Mar 03;: Authors: Ren L, Hong ES, Mendoza A, Issaq S, Tran Hoang C, Lizardo M, LeBlanc A, Khanna C Abstract Cancer development and progression are characterized by complex molecular events. The acquisition of these events is primarily believed to result from alterations in gene and protein expression/function. Recent studies have also suggested the role of metabolic alterations, or "metabolic reprogramming," that may similarly contribute to these events. Indeed, our previous investigations in osteosarcoma (OS) identified metabolic changes uniquely linked to metastasis. Based on those findings, here we sought to build a more detailed understanding of the specific alterations in metabolites or metabolic pathways that may be responsible for the observed metastasis-associated metabolic alterations, suggested by gene expression data. This was pursued using a combination of high-throughput liquid- and gas-chromatography-based mass spectrometry (LC/MS and GC/MS) for a global metabolic profiling/subtraction of four pairs of high/low metastatic OS cell lines. By comparing the identity and level of the metabolites between high/low metastatic cells, several metabolic pathways were identified to be differentially activated, such as arginine, glutathione, inositol and fatty acid metabolic pathways. To further interrogate these results, we investigated the effects of inositol pathway dysregulation, through the exposure of metastatic OS cells to IP6 (inositol hexaphosphate). Although IP6 exposures had modest to minimal effects on cell proliferation, we observed reduced cellular glycolysis, down-regulation of PI3K/Akt signaling and suppression of OS metastatic progression. Collectively these data supported further investigation of metabolic sensitivities as anti-metastatic strategies in a clinical setting as well as investigation of altered metabolomics associated with metastatic progression. PMID: 28404949 [PubMed - as supplied by publisher]