PubMed

Related Articles Metabolomic Applications to the Characterization of the Mode-of-Action of CDK Inhibitors. Methods Mol Biol. 2016;1336:211-223 Authors: Palomino-Schätzlein M, Pineda-Lucena A Abstract Cyclin-dependent kinases (CDKs) regulate cell cycle progression, and some of them are also involved in the control of cellular transcription. Dysregulation of these critical cellular processes, due to the aberrant expression of some of these proteins, is common in many neoplastic malignancies. Consequently, the development of chemical compounds capable of inhibiting the biological activity of CDKs represents an attractive strategy in the anticancer area. CDK inhibition can trigger apoptosis and could be particularly useful in hematological malignancies, which are more sensitive to inhibition of cell cycle and apoptosis induction. Over the last few years, a number of pharmacological inhibitors of CDKs (CDKIs) belonging to different chemical families have been developed, and some of them have been tested in clinical trials. Given the complexity of the role of CDKs in cell functioning, it would be desirable to develop new tools that could facilitate a better understanding of the new insights into CDK functions and the mode-of-actions of CDKIs. In this context, this chapter describes an experimental approach to evaluate the metabolic consequences of CDKIs at the cellular level based on metabolomics by NMR. More specifically, a description of a strategy to characterize the biochemical effects of CDKIs acting on mammalian cells is provided, including protocols for the extraction of hydrophilic and lipophilic metabolites, the acquisition of 1D and 2D metabolomic Nuclear Magnetic Resonance (NMR) experiments, the identification and quantification of metabolites, and the annotation of the results in the context of biochemical pathways. PMID: 26231718 [PubMed - as supplied by publisher]

Related Articles The Role of the Epigenome in Translating Neighborhood Disadvantage Into Health Disparities. Curr Environ Health Rep. 2015 Jun;2(2):163-170 Authors: Olden K, Olden HA, Lin YS Abstract The possible causal role of the environment in health disparities is not well understood, even though it has been a national priority for many years. Progress to investigate the relationship between genetics, environmental exposures, and health outcomes has been hampered by the lack of analytical tools to quantify the combined or cumulative effect of multiple chemical and non-chemical stressors on gene expression. The studies cited here provide a strong rationale for using epigenomic analysis to assess cumulative risk from multiple environmental exposures over the life course. The environment-specific "imprints" on the genome, coupled with transcriptomics and metabolomics, can be used to advance our understanding of the relationship between neighborhood disadvantage and health disparities. PMID: 26231365 [PubMed - as supplied by publisher]

20 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 2015/08/01PubMed 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.

16 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 2015/07/30PubMed 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.

Related Articles Metabolic profiling of breast cancer: Differences in central metabolism between subtypes of breast cancer cell lines. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Jul 14;1000:95-104 Authors: Willmann L, Schlimpert M, Halbach S, Erbes T, Stickeler E, Kammerer B Abstract Although the concept of aerobic glycolysis in cancer was already reported in the 1930s by Otto Warburg, the understanding of metabolic pathways remains challenging especially due to the heterogeneity of cancer. In consideration of four different time points (1, 2, 4, and 7 days of incubation), GC-MS profiling of metabolites was performed on cell extracts and supernatants of breast cancer cell lines (MDA-MB-231, -453, BT-474) with different sub classification and the breast epithelial cell line MCF-10A. To the exclusion of trypsinization, direct methanolic extraction, cell scraping and cell disruption was executed to obtain central metabolites. Major differences in biochemical pathways have been observed in the breast cancer cell lines compared to the breast epithelial cell line, as well as between the breast cancer cell lines themselves. Characteristics of breast cancer subtypes could be correlated to their individual metabolic profiles. PLS-DA revealed the discrimination of breast cancer cell lines from MCF-10A based on elevated amino acid levels. The observed metabolic signatures have great potential as biomarker for breast cancer as well as an improved understanding of subtype specific phenomenons of breast cancer. PMID: 26218769 [PubMed - as supplied by publisher]

Related Articles Lipid and protein maps defining arterial layers in atherosclerotic aorta. Data Brief. 2015 Sep;4:328-31 Authors: Martin-Lorenzo M, Balluff B, Maroto AS, Carreira RJ, van Zeijl RJ, Gonzalez-Calero L, de la Cuesta F, Barderas MG, Lopez-Almodovar LF, Padial LR, McDonnell LA, Vivanco F, Alvarez-Llamas G Abstract Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI) accounts with the unique advantage of analyzing proteins and metabolites (lipids) while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media) and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press); M. Martin-Lorenzo et al., J. Proteomics 108 (2014) 465-468.) [1,2]. PMID: 26217810 [PubMed]

Related Articles Data from identification of diagnostic biomarkers and metabolic pathway shifts of heat-stressed lactating dairy cows. Data Brief. 2015 Sep;4:90-5 Authors: Tian H, Wang W, Zheng N, Cheng J, Li S, Zhang Y, Wang J Abstract Controlling heat stress (HS) is a global challenge for the dairy industry. In this work, an integrated metabolomics and lipidomics approach using (1)H nuclear magnetic resonance (NMR) and ultra-fast LC-MS in combination with multivariate analyses was employed to investigate the discrimination of plasma metabolic profiles between HS-free and HS lactating dairy cows. Here we provide the information about the acquiring and processing of raw data obtained by (1)H NMR and LC-MS techniques. The data of present study are related to the research article "Identification of diagnostic biomarkers and metabolic pathway shifts of heat-stressed lactating dairy cows" in the Journal of Proteomics (Tian et al., J. Proteomics, (2015), doi:10.1016/j.jprot.2015.04.014). PMID: 26217769 [PubMed]

Related Articles Data in support of enhancing metabolomics research through data mining. Data Brief. 2015 Jun;3:155-64 Authors: Martínez-Arranz I, Mayo R, Pérez-Cormenzana M, Mincholé I, Salazar L, Alonso C, Mato JM Abstract Metabolomics research has evolved considerably, particularly during the last decade. Over the course of this evolution, the interest in this 'omic' discipline is now more evident than ever. However, the future of metabolomics will depend on its capability to find biomarkers. For that reason, data mining constitutes a challenging task in metabolomics workflow. This work has been designed in support of the research article entitled "Enhancing metabolomics research through data mining", which proposed a methodological data handling guideline. An aging research in healthy population was used as a guiding thread to illustrate this process. Here we provide a further interpretation of the obtained statistical results. We also focused on the importance of graphical visualization tools as a clue to understand the most common univariate and multivariate data analyses applied in metabolomics. PMID: 26217737 [PubMed]

Related Articles Spatially resolved in vivo plant metabolomics by laser ablation-based mass spectrometry imaging (MSI) techniques: LDI-MSI and LAESI. Front Plant Sci. 2015;6:471 Authors: Bartels B, Svatoš A Abstract This short review aims to summarize the current developments and applications of mass spectrometry-based methods for in situ profiling and imaging of plants with minimal or no sample pre-treatment or manipulation. Infrared-laser ablation electrospray ionization and UV-laser desorption/ionization methods are reviewed. The underlying mechanisms of the ionization techniques-namely, laser ablation of biological samples and electrospray ionization-as well as variations of the LAESI ion source for specific targets of interest are described. PMID: 26217345 [PubMed]

Related Articles The quest for tolerant varieties: the importance of integrating "omics" techniques to phenotyping. Front Plant Sci. 2015;6:448 Authors: Zivy M, Wienkoop S, Renaut J, Pinheiro C, Goulas E, Carpentier S Abstract The primary objective of crop breeding is to improve yield and/or harvest quality while minimizing inputs. Global climate change and the increase in world population are significant challenges for agriculture and call for further improvements to crops and the development of new tools for research. Significant progress has been made in the molecular and genetic analysis of model plants. However, is science generating false expectations? Are 'omic techniques generating valuable information that can be translated into the field? The exploration of crop biodiversity and the correlation of cellular responses to stress tolerance at the plant level is currently a challenge. This viewpoint reviews concisely the problems one encounters when working on a crop and provides an outline of possible workflows when initiating cellular phenotyping via "-omic" techniques (transcriptomics, proteomics, metabolomics). PMID: 26217344 [PubMed]

Related Articles Potential of metabolomics to reveal Burkholderia cepacia complex pathogenesis and antibiotic resistance. Front Microbiol. 2015;6:668 Authors: Shommu NS, Vogel HJ, Storey DG Abstract The Burkholderia cepacia complex (Bcc) is a collection of closely related, genetically distinct, ecologically diverse species known to cause life-threatening infections in cystic fibrosis (CF) patients. By virtue of a flexible genomic structure and diverse metabolic activity, Bcc bacteria employ a wide array of virulence factors for pathogenesis in CF patients and have developed resistance to most of the commonly used antibiotics. However, the mechanism of pathogenesis and antibiotic resistance is still not fully understood. This mini review discusses the established and potential virulence determinants of Bcc and some of the contemporary strategies including transcriptomics and proteomics used to identify these traits. We also propose the application of metabolic profiling, a cost-effective modern-day approach to achieve new insights. PMID: 26217312 [PubMed]

Related Articles Selenocysteine-independent suppression of UGA codons in the archaeon Methanococcus maripaludis. Biochim Biophys Acta. 2015 Jul 24; Authors: Seyhan D, Jehmlich N, von Bergen M, Fersch J, Rother M Abstract BACKGROUND: Proteins containing selenocysteine (sec) are found in Bacteria, Eukarya, and Archaea. While selenium-dependence of methanogenesis from H2+CO2 in the archaeon Methanococcus maripaludis JJ is compensated by induction of a set of cysteine-containing homologs, growth on formate is abrogated in the absence of sec due to the dependence of formate dehydrogenase (Fdh) on selenium. Despite this dependence, formate-dependent growth occurs after prolonged incubation of M. maripaludis mutants lacking sec. METHODS: To study this phenomenon, a M. maripaludis strain with only one Fdh isoform and an FdhA selenoprotein C-terminally tagged for affinity enrichment was constructed. Factors required for sec synthesis were deleted in this strain and translation of UGA in fdhA was analyzed physiologically, enzymatically, immunologically, and via mass spectrometry. RESULTS: M. maripaludis JJ mutants lacking sec synthesis grew at least five times more slowly than the wild type on formate due to a 20-35-fold reduction of Fdh activity. The enzyme in the mutant strains lacked sec but was still produced as a full-length protein. Peptide mass spectrometry revealed that both cysteine (cys) and tryptophan (trp) were inserted at the UGA encoding sec without apparent mutations in tRNA(cys) or tRNA(trp), respectively. CONCLUSIONS: We demonstrate that M. maripaludis has the inherent capacity to translate UGA with cys and trp; other mechanisms to replace sec with cys in the absence of selenium could thereby be ruled out. GENERAL SIGNIFICANCE: This study exemplifies how an organism uses the inherent flexibility in its canonical protein synthesis machinery to recover some activity of an essential selenium-dependent enzyme in the absence of sec. PMID: 26215786 [PubMed - as supplied by publisher]

Related Articles Hyperpolarized NMR of plant and cancer cell extracts at natural abundance. Analyst. 2015 Jul 28; Authors: Dumez JN, Milani J, Vuichoud B, Bornet A, Lalande-Martin J, Tea I, Yon M, Maucourt M, Deborde C, Moing A, Frydman L, Bodenhausen G, Jannin S, Giraudeau P Abstract Natural abundance (13)C NMR spectra of biological extracts are recorded in a single scan provided that the samples are hyperpolarized by dissolution dynamic nuclear polarization combined with cross polarization. Heteronuclear 2D correlation spectra of hyperpolarized breast cancer cell extracts can also be obtained in a single scan. Hyperpolarized NMR of extracts opens many perspectives for metabolomics. PMID: 26215673 [PubMed - as supplied by publisher]

Related Articles Signaling network of lipids as a comprehensive scaffold for omics data integration in sputum of COPD patients. Biochim Biophys Acta. 2015 Jul 24; Authors: Azimzadeh S, Mirzaie M, Jafari M, Mehrani H, Shariati P, Khodabandeh M Abstract Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive inflammatory condition that has been linked to the dysregulation of many metabolic pathways including lipid biosynthesis. How lipid metabolism could affect disease progression in smokers with COPD remains unclear. We cross-examined the transcriptomics, proteomics, metabolomics, and phenomics data available on the public domain to elucidate the mechanisms by which lipid metabolism is perturbed in COPD. We reconstructed a sputum lipid COPD (SpLiCO) signaling network utilizing active/inactive, and functional/dysfunctional lipid-mediated signaling pathways to explore how lipid-metabolism could promote COPD pathogenesis in smokers. SpLiCO was further utilized to investigate signal amplifiers, distributers, propagators, feed-forward and/or -back loops that link COPD disease severity and hypoxia to disruption in the metabolism of sphingolipids, fatty acids and energy. Also, hypergraph analysis and calculations for dependency of molecules identified several important nodes in the network with modular regulatory and signal distribution activities. Our systems-based analyses indicate that arachidonic acid is a critical and early signal distributer that is upregulated by the sphingolipid signaling pathway in COPD, while hypoxia plays a critical role in the elevated dependency to glucose as a major energy source. Integration of SpLiCo and clinical data shows a strong association between hypoxia and the upregulation of sphingolipids in smokers with emphysema, vascular disease, hypertension and those with increased risk of lung cancer. PMID: 26215076 [PubMed - as supplied by publisher]

Related Articles The gentio-oligosaccharide gentiobiose functions in the modulation of bud dormancy in the herbaceous perennial Gentiana. Plant Cell. 2014 Oct;26(10):3949-63 Authors: Takahashi H, Imamura T, Konno N, Takeda T, Fujita K, Konishi T, Nishihara M, Uchimiya H Abstract Bud dormancy is an adaptive strategy that perennials use to survive unfavorable conditions. Gentians (Gentiana), popular alpine flowers and ornamentals, produce overwintering buds (OWBs) that can persist through the winter, but the mechanisms regulating dormancy are currently unclear. In this study, we conducted targeted metabolome analysis to obtain clues about the metabolic mechanisms involved in regulating OWB dormancy. Multivariate analysis of metabolite profiles revealed metabolite patterns characteristic of dormant states. The concentrations of gentiobiose [β-D-Glcp-(1→6)-D-Glc] and gentianose [β-D-Glcp-(1→6)-D-Glc-(1→2)-d-Fru] significantly varied depending on the stage of OWB dormancy, and the gentiobiose concentration increased prior to budbreak. Both activation of invertase and inactivation of β-glucosidase resulted in gentiobiose accumulation in ecodormant OWBs, suggesting that gentiobiose is seldom used as an energy source but is involved in signaling pathways. Furthermore, treatment with exogenous gentiobiose induced budbreak in OWBs cultured in vitro, with increased concentrations of sulfur-containing amino acids, GSH, and ascorbate (AsA), as well as increased expression levels of the corresponding genes. Inhibition of GSH synthesis suppressed gentiobiose-induced budbreak accompanied by decreases in GSH and AsA concentrations and redox status. These results indicate that gentiobiose, a rare disaccharide, acts as a signal for dormancy release of gentian OWBs through the AsA-GSH cycle. PMID: 25326293 [PubMed - indexed for MEDLINE]

Related Articles Development and application of a comparative fatty acid analysis method to investigate voriconazole-induced hepatotoxicity. Clin Chim Acta. 2015 Jan 1;438:126-34 Authors: Chen GY, Chiu HH, Lin SW, Tseng YJ, Tsai SJ, Kuo CH Abstract BACKGROUND: As fatty acids play an important role in biological regulation, the profiling of fatty acid expression has been used to discover various disease markers and to understand disease mechanisms. This study developed an effective and accurate comparative fatty acid analysis method using differential labeling to speed up the metabolic profiling of fatty acids. METHODS: Fatty acids were derivatized with unlabeled (D0) or deuterated (D3) methanol, followed by GC-MS analysis. The comparative fatty acid analysis method was validated using a series of samples with different ratios of D0/D3-labeled fatty acid standards and with mouse liver extracts. RESULTS: Using a lipopolysaccharide (LPS)-treated mouse model, we found that the fatty acid profiles after LPS treatment were similar between the conventional single-sample analysis approach and the proposed comparative approach, with a Pearson's correlation coefficient of approximately 0.96. We applied the comparative method to investigate voriconazole-induced hepatotoxicity and revealed the toxicity mechanism as well as the potential of using fatty acids as toxicity markers. CONCLUSIONS: In conclusion, the comparative fatty acid profiling technique was determined to be fast and accurate and allowed the discovery of potential fatty acid biomarkers in a more economical and efficient manner. PMID: 25150729 [PubMed - indexed for MEDLINE]

Related Articles Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever. Elife. 2014;3 Authors: Näsström E, Vu Thieu NT, Dongol S, Karkey A, Voong Vinh P, Ha Thanh T, Johansson A, Arjyal A, Thwaites G, Dolecek C, Basnyat B, Baker S, Antti H Abstract The host-pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections. PMID: 24902583 [PubMed - indexed for MEDLINE]

Related Articles Analytical strategies for studying stem cell metabolism. Front Biol (Beijing). 2015 Apr;10(2):141-153 Authors: Arnold JM, Choi WT, Sreekumar A, Maletić-Savatić M Abstract Owing to their capacity for self-renewal and pluripotency, stem cells possess untold potential for revolutionizing the field of regenerative medicine through the development of novel therapeutic strategies for treating cancer, diabetes, cardiovascular and neurodegenerative diseases. Central to developing these strategies is improving our understanding of biological mechanisms responsible for governing stem cell fate and self-renewal. Increasing attention is being given to the significance of metabolism, through the production of energy and generation of small molecules, as a critical regulator of stem cell functioning. Rapid advances in the field of metabolomics now allow for in-depth profiling of stem cells both in vitro and in vivo, providing a systems perspective on key metabolic and molecular pathways which influence stem cell biology. Understanding the analytical platforms and techniques that are currently used to study stem cell metabolomics, as well as how new insights can be derived from this knowledge, will accelerate new research in the field and improve future efforts to expand our understanding of the interplay between metabolism and stem cell biology. PMID: 26213533 [PubMed - as supplied by publisher]

Related Articles Using fragmentation trees and mass spectral trees for identifying unknown compounds in metabolomics. Trends Analyt Chem. 2015 Jun 1;69:52-61 Authors: Vaniya A, Fiehn O Abstract Identification of unknown metabolites is the bottleneck in advancing metabolomics, leaving interpretation of metabolomics results ambiguous. The chemical diversity of metabolism is vast, making structure identification arduous and time consuming. Currently, comprehensive analysis of mass spectra in metabolomics is limited to library matching, but tandem mass spectral libraries are small compared to the large number of compounds found in the biosphere, including xenobiotics. Resolving this bottleneck requires richer data acquisition and better computational tools. Multi-stage mass spectrometry (MSn) trees show promise to aid in this regard. Fragmentation trees explore the fragmentation process, generate fragmentation rules and aid in sub-structure identification, while mass spectral trees delineate the dependencies in multi-stage MS of collision-induced dissociations. This review covers advancements over the past 10 years as a tool for metabolite identification, including algorithms, software and databases used to build and to implement fragmentation trees and mass spectral annotations. PMID: 26213431 [PubMed - as supplied by publisher]

Related Articles Metabolic profiling of a range of peach fruit varieties reveals high metabolic diversity and commonalities and differences during ripening. Food Chem. 2016 Jan 1;190:879-88 Authors: Monti LL, Bustamante CA, Osorio S, Gabilondo J, Borsani J, Lauxmann MA, Maulión E, Valentini G, Budde CO, Fernie AR, Lara MV, Drincovich MF Abstract Peach (Prunus persica) fruits from different varieties display differential organoleptic and nutritional properties, characteristics related to their chemical composition. Here, chemical biodiversity of peach fruits from fifteen varieties, at harvest and after post-harvest ripening, was explored by gas chromatography-mass spectrometry. Metabolic profiling revealed that metabolites involved in organoleptic properties (sugars, organic and amino acids), stress tolerance (raffinose, galactinol, maltitol), and with nutritional properties (amino, caffeoylquinic and dehydroascorbic acids) displayed variety-dependent levels. Peach varieties clustered into four groups: two groups of early-harvest varieties with higher amino acid levels; two groups of mid- and late-harvest varieties with higher maltose levels. Further separation was mostly dependent on organic acids/raffinose levels. Variety-dependent and independent metabolic changes associated with ripening were detected; which contribute to chemical diversity or can be used as ripening markers, respectively. The great variety-dependent diversity in the content of metabolites that define fruit quality reinforces metabolomics usage as a tool to assist fruit quality improvement in peach. PMID: 26213052 [PubMed - in process]