PubMed

Related Articles The Proteome of Tetrasphaera elongata is adapted to Changing Conditions in Wastewater Treatment Plants. Proteomes. 2019 Apr 25;7(2): Authors: Herbst FA, Dueholm MS, Wimmer R, Nielsen PH Abstract The activated sludge in wastewater treatment plants (WWTP) designed for enhanced biological phosphorus removal (EBPR) experiences periodically changing nutrient and oxygen availability. Tetrasphaera is the most abundant genus in Danish WWTP and represents up to 20-30% of the activated sludge community based on 16S rRNA amplicon sequencing and quantitative fluorescence in situ hybridization analyses, although the genus is in low abundance in the influent wastewater. Here we investigated how Tetrasphaera can successfully out-compete most other microorganisms in such highly dynamic ecosystems. To achieve this, we analyzed the physiological adaptations of the WWTP isolate T. elongata str. LP2 during an aerobic to anoxic shift by label-free quantitative proteomics and NMR-metabolomics. Escherichia coli was used as reference organism as it shares several metabolic capabilities and is regularly introduced to wastewater treatment plants without succeeding there. When compared to E. coli, only minor changes in the proteome of T. elongata were observed after the switch to anoxic conditions. This indicates that metabolic pathways for anaerobic energy harvest were already expressed during the aerobic growth. This allows continuous growth of Tetrasphaera immediately after the switch to anoxic conditions. Metabolomics furthermore revealed that the substrates provided were exploited far more efficiently by Tetrasphaera than by E. coli. These results suggest that T. elongata prospers in the dynamic WWTP environment due to adaptation to the changing environmental conditions. PMID: 31027192 [PubMed]

Related Articles Surfactant Lipidomics of Alveolar Lavage Fluid in Mice Based on Ultra-High-Performance Liquid Chromatography Coupled to Hybrid Quadrupole-Exactive Orbitrap Mass Spectrometry. Metabolites. 2019 Apr 25;9(4): Authors: Yang R, Zhang Y, Qian W, Peng L, Lin L, Xu J, Xie T, Ji J, Zhan X, Shan J Abstract Surfactant lipid metabolism is closely related to pulmonary diseases. Lipid metabolism disorder can cause lung diseases, vice versa. With this rationale, a useful method was established in this study to determine the lipidome in bronchoalveolar lavage fluid (BALF) of mice. The lipid components in BALF were extracted by liquid-liquid extraction (methanol and methyl tert-butyl ether, and water). Ultra-high-performance liquid chromatography coupled to hybrid Quadrupole-Exactive Orbitrap mass spectrometry was used to analyze the extracted samples, which showed a broad scanning range of 215-1800 m/z. With MS-DIAL software and built-in LipidBlast database, we identified 38 lipids in positive, and 31 lipids in negative, ion mode, including lysophosphatidylcholine (lysoPC), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), etc. Then, the changes of lipids in BALF of mice with acute lung injury (ALI) induced by lipopolysaccharide (LPS) was investigated, which may contribute to further exploration of the pathogenesis of ALI. PMID: 31027159 [PubMed]

21 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 2019/04/27PubMed 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.

Related Articles Effect of CAX1a TILLING mutations and calcium concentration on some primary metabolism processes in Brassica rapa plants. J Plant Physiol. 2019 Apr 18;237:51-60 Authors: Navarro-León E, Ruiz JM, Albacete A, Blasco B Abstract Cation/H+ exchanger transporters (CAXs) are crucial in Ca2+ homeostasis and in the generation of Ca2+ profiles involved in signalling processes. Given the crucial role of CAX1 in Ca2+ homeostasis, CAX1 modifications could have effects on plant metabolism. Three Brassica rapa mutants for CAX1 were obtained through TILLING. The aim of this work is to assess the effect of the different mutations and different Ca2+ doses on plant metabolism. For this, the mutants and the parental line were grown under low, control and high Ca2+ doses and parameters related to nitrogen (N) and tricarboxylic acid (TCA) metabolisms, and amino acid (AAs) and phytohormone profiles were measured. The results show that BraA.cax1a mutations affect metabolism especially under high Ca2+ dose. Thus, BraA.cax1a-7 inhibited some N metabolism enzymes and activated photorespiration activity. On the opposite side, BraA.cax1a-12 mutation provides a better tolerance to high Ca2+ dose. This tolerance could be provided by an improved N and TCA metabolisms enzymes, and a higher glutamate, malate, indole-3-acetic acid and abscisic acid concentrations. Therefore, BraA.cax1a-12 mutation could be used for B. rapa improving; the metabolomics changes observed in this mutant could be responsible for a better tolerance to high Ca2+. PMID: 31022665 [PubMed - as supplied by publisher]

Related Articles NMR for sample quality assessment in metabolomics. N Biotechnol. 2019 Apr 22;: Authors: Ghini V, Quaglio D, Luchinat C, Turano P Abstract The EU Framework 7 project SPIDIA was the occasion for development of NMR approaches to evaluate the impact of different pre-analytical treatments on the quality of biological samples dedicated to metabolomics. Systematic simulation of different pre-analytical procedures was performed on urine and blood serum and plasma. Here we review the key aspects of these studies that have led to the development of CEN technical specifications, to be translated into ISO/IS in the course of the EU Horizon 2020 project SPIDIA4P. Inspired by the SPIDIA results, follow-up research was performed, extending the analysis to different sample types and to the different effects of long-term storage. The latter activity was in conjunction with the local European da Vinci Biobank. These results (which partially contributed to the ANNEX of CEN/TS 16945 "MOLECULAR IN VITRO DIAGNOSTIC EXAMINATIONS - SPECIFICATIONS FOR PRE-EXAMINATION PROCESSES FOR METABOLOMICS IN URINE, VENOUS BLOOD SERUM AND PLASMA") are presented in detail. PMID: 31022482 [PubMed - as supplied by publisher]

Related Articles Targeted metabolomics analysis of maternal-placental-fetal metabolism in pregnant swine reveals links in fetal bile acid homeostasis and sulfation capacity. Am J Physiol Gastrointest Liver Physiol. 2019 Apr 25;: Authors: Wang P, Zhong H, Song Y, Yuan P, Li Y, Lin S, Zhang X, Li J, Che L, Feng B, Lin Y, Xu S, Zhuo Y, Tian G, Chen D, Wu, Burrin DG, Fang Z Abstract Cholestasis of pregnancy endangers fetal and neonatal survival, yet systematic knowledge of the cause and effect of disrupted bile acid (BA) homeostasis in pregnancy is limited. Here we show that gestation stage-associated BA dysregulation in swine correlated with fetal death resulting from compromised capacity for BA secretion and increased alternative systemic efflux. The balance of BA input and output in the developing uterus suggested little uptake and metabolism of maternal BA by the placenta-fetus unit, implying a protection role of placenta in preventing maternal BA transported into fetus. We showed that the maternal origin of BA accounted for the increase in placental TBA leading to dysregulated expression of genes involved in BA transport and potentially impaired transplacental export of fetus-derived BA. Correspondingly, the secondary BA, mainly derived from the mother, gradually decreased in fetus. Finally, we identified that sulfation rather than glucuronidation played pivotal roles in maintaining BA homeostasis of developing fetus. These novel and systemic findings contribute to a whole picture of BA metabolism in pregnancy, and provide new insights into mechanisms responsible for maternal and fetal BA homeostasis. PMID: 31021171 [PubMed - as supplied by publisher]

Related Articles Comprehensive transcriptomics, proteomics, and metabolomics analyses of the mechanisms regulating tiller production in low-tillering wheat. Theor Appl Genet. 2019 Apr 16;: Authors: Wang Z, Shi H, Yu S, Zhou W, Li J, Liu S, Deng M, Ma J, Wei Y, Zheng Y, Liu Y Abstract KEY MESSAGE: Tiller development in low-tillering wheat is related to several differentially expressed genes, proteins, and metabolites, as determined by an integrated omics approach combining transcriptome analysis, iTRAQ, and HPLC-MS on multiple NILs. Tillering is an important aspect of plant morphology that affects spike number, thereby contributing to the final crop yield. However, the mechanisms inhibiting tiller production in low-tillering wheat are poorly characterized. To investigate this aspect of wheat biology, two pairs of near-isogenic lines were developed, and an integrated omics approach combining transcriptome analysis, isobaric tags for relative and absolute quantification, and high-performance liquid chromatography-mass spectrometry were used to compare the free-tillering and low-tillering caused by an allele at Qltn.sicau-2D in wheat samples. Overall, 474 genes, 166 proteins, and 28 metabolites were identified as tillering-associated differentially expressed genes, proteins, and metabolites (DEGs, DEPs, and DEMs, respectively). Functional analysis indicated that the abundance of DEGs/DEPs/DEMs was related to lignin and cellulose metabolism, cell division, cell cycle processes, and glycerophospholipid metabolism; three transcription factor families, GRAS, GRF, and REV, might be related to the decrease in tillering in low-tillering wheat. These findings contribute to improve our understanding of the mechanisms responsible for the inhibition of tiller development in low-tillering wheat cultivars. PMID: 31020386 [PubMed - as supplied by publisher]

Related Articles Metabolic Modeling of Cystic Fibrosis Airway Communities Predicts Mechanisms of Pathogen Dominance. mSystems. 2019 Mar-Apr;4(2): Authors: Henson MA, Orazi G, Phalak P, O'Toole GA Abstract Cystic fibrosis (CF) is a fatal genetic disease characterized by chronic lung infections due to aberrant mucus production and the inability to clear invading pathogens. The traditional view that CF infections are caused by a single pathogen has been replaced by the realization that the CF lung usually is colonized by a complex community of bacteria, fungi, and viruses. To help unravel the complex interplay between the CF lung environment and the infecting microbial community, we developed a community metabolic model comprised of the 17 most abundant bacterial taxa, which account for >95% of reads across samples, from three published studies in which 75 sputum samples from 46 adult CF patients were analyzed by 16S rRNA gene sequencing. The community model was able to correctly predict high abundances of the "rare" pathogens Enterobacteriaceae, Burkholderia, and Achromobacter in three patients whose polymicrobial infections were dominated by these pathogens. With these three pathogens removed, the model correctly predicted that the remaining 43 patients would be dominated by Pseudomonas and/or Streptococcus. This dominance was predicted to be driven by relatively high monoculture growth rates of Pseudomonas and Streptococcus as well as their ability to efficiently consume amino acids, organic acids, and alcohols secreted by other community members. Sample-by-sample heterogeneity of community composition could be qualitatively captured through random variation of the simulated metabolic environment, suggesting that experimental studies directly linking CF lung metabolomics and 16S sequencing could provide important insights into disease progression and treatment efficacy. IMPORTANCE Cystic fibrosis (CF) is a genetic disease in which chronic airway infections and lung inflammation result in respiratory failure. CF airway infections are usually caused by bacterial communities that are difficult to eradicate with available antibiotics. Using species abundance data for clinically stable adult CF patients assimilated from three published studies, we developed a metabolic model of CF airway communities to better understand the interactions between bacterial species and between the bacterial community and the lung environment. Our model predicted that clinically observed CF pathogens could establish dominance over other community members across a range of lung nutrient conditions. Heterogeneity of species abundances across 75 patient samples could be predicted by assuming that sample-to-sample heterogeneity was attributable to random variations in the CF nutrient environment. Our model predictions provide new insights into the metabolic determinants of pathogen dominance in the CF lung and could facilitate the development of improved treatment strategies. PMID: 31020043 [PubMed]

Related Articles Ketamine's Effects on the Glutamatergic and GABAergic Systems: A Proteomics and Metabolomics Study in Mice. Mol Neuropsychiatry. 2019 Mar;5(1):42-51 Authors: Weckmann K, Deery MJ, Howard JA, Feret R, Asara JM, Dethloff F, Filiou MD, Labermaier C, Maccarrone G, Lilley KS, Mueller M, Turck CW Abstract Ketamine, a noncompetitive, voltage-dependent N-Methyl-D-aspartate receptor (NMDAR) antagonist, has been shown to have a rapid antidepressant effect and is used for patients experiencing treatment-resistant depression. We carried out a time-dependent targeted mass spectrometry-based metabolomics profiling analysis combined with a quantitative based on in vivo 15N metabolic labeling proteome comparison of ketamine- and vehicle-treated mice. The metabolomics and proteomics datasets were used to further elucidate ketamine's mode of action on the gamma-aminobutyric acid (GABA)ergic and glutamatergic systems. In addition, myelin basic protein levels were analyzed by Western Blot. We found altered GABA, glutamate and glutamine metabolite levels and ratios as well as increased levels of putrescine and serine - 2 positive modulators of the NMDAR. In addition, GABA receptor (GABAR) protein levels were reduced, whereas the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunit Gria2 protein levels were increased upon ketamine treatment. The significantly altered metabolite and protein levels further significantly correlated with the antidepressant-like behavior, which was assessed using the forced swim test. In conclusion and in line with previous research, our data indicate that ketamine impacts the AMPAR subunit Gria2 and results in decreased GABAergic inhibitory neurotransmission leading to increased excitatory neuronal activity. PMID: 31019917 [PubMed]

Related Articles Metabolomic profiling to identify effects of dietary calcium reveal the influence of the individual and postprandial dynamics on the canine plasma metabolome. J Nutr Sci. 2019;8:e13 Authors: Allaway D, Gilham M, Wagner-Golbs A, Maldonado SG, Haydock R, Colyer A, Stockman J, Watson P Abstract Short-term feeding studies have highlighted a phenomenon in Ca regulation that raises concerns around Ca absorption in dogs that may make an impact on commercial diets near to the maximum recommended level. A recent study to determine responses in dogs fed one of two diets differing in dietary Ca over 40 weeks found no evidence to suggest a concern across a range of biological parameters hypothesised to be affected by Ca. Unforeseen consequences of dietary Ca could have occurred and metabolic profiling was deemed a suitable data-driven approach to identify effects of dietary Ca. The objectives were to compare the fasted plasma metabolome (sampled at 8-week intervals over 40 weeks) of dogs fed one of two diets, near to the minimum and maximum recommended levels of dietary Ca. Comparisons with the control diet were also investigated across the postprandial time course (1-4 h) following acute (1 d) and long-term (24 weeks) feeding of the test diet. Comparing fasted plasma samples at each time point, no significant effect (adjusted P < 0·05) of diet on metabolites was observed. In the postprandial state, only phosphate was consistently different between diets and was explained by additional dietary P to maintain Ca:P. Metabolic profiling analysis supports the view that the dietary Ca upper limit is safe. Additionally, the canine plasma metabolome was characterised, providing insights into the stability of individual profiles across 40 weeks, the response to consumption of a nutritionally complete meal over a 4 h postprandial time course and different kinetic categories of postprandial absorption. PMID: 31019684 [PubMed]

Related Articles Deep undepleted human serum proteome profiling toward biomarker discovery for Alzheimer's disease. Clin Proteomics. 2019;16:16 Authors: Dey KK, Wang H, Niu M, Bai B, Wang X, Li Y, Cho JH, Tan H, Mishra A, High AA, Chen PC, Wu Z, Beach TG, Peng J Abstract Background: Blood-based protein measurement is a routine practice for detecting biomarkers in human disease. Comprehensive profiling of blood/plasma/serum proteome is a challenge due to an extremely large dynamic range, as exemplified by a small subset of highly abundant proteins. Antibody-based depletion of these abundant proteins alleviates the problem but introduces experimental variations. We aimed to establish a method for direct profiling of undepleted human serum and apply the method toward biomarker discovery for Alzheimer's disease (AD), as AD is the most common form of dementia without available blood-based biomarkers in clinic. Methods: We present an ultra-deep analysis of undepleted human serum proteome by combining the latest 11-plex tandem-mass-tag (TMT) labeling, exhaustive two-dimensional liquid chromatography (LC/LC) fractionation (the 1st LC: 3 h for 180 fractions, and the 2nd LC: 3 h gradient per fraction), coupled with high resolution tandem mass spectrometry (MS/MS). AD (n = 6) and control (n = 5) sera were analyzed in this pilot study. In addition, we implemented a multiplexed targeted LC-MS3 method (TOMAHAQ) for the validation of selected target proteins. Results: The TMT-LC/LC-MS/MS platform is capable of analyzing 4826 protein components (4368 genes), covering at least 6 orders of magnitude in dynamic range, representing one of the deepest serum proteome analysis. We defined intra- and inter- group variability in the AD and control groups. Statistical analysis revealed differentially expressed proteins in AD (26 decreased and 4 increased). Notably, these altered proteins are enriched in the known pathways of mitochondria, fatty acid beta oxidation, and AGE/RAGE. Finally, we set up a TOMAHAQ method to confirm the decrease of PCK2 and AK2 in our AD samples. Conclusions: Our results show an ultra-deep serum discovery study by TMT-LC/LC-MS/MS, and a validation experiment by TOMAHAQ targeted LC-MS3. The MS-based discovery and validation methods are of general use for biomarker discovery from complex biofluids (e.g. serum proteome). This pilot study also identified deregulated proteins, in particular proteins associated with mitochondrial function in the AD serum samples. These proteins may serve as novel AD candidate biomarkers. PMID: 31019427 [PubMed]

Related Articles The mercapturomic profile of health and non-communicable diseases. High Throughput. 2019 Apr 23;8(2): Authors: Gonçalves-Dias C, Morello J, Semedo V, Correia MJ, Coelho NR, Monteiro EC, Antunes AMM, Pereira SA Abstract The mercapturate pathway is a unique metabolic circuitry that detoxifies electrophiles upon adducts formation with glutathione. Since its discovery over a century ago, most of the knowledge on the mercapturate pathway has been provided from biomonitoring studies on environmental exposure to toxicants. However, the mercapturate pathway-related metabolites that is formed in humans-the mercapturomic profile-in health and disease is yet to be established. In this paper, we put forward the hypothesis that these metabolites are key pathophysiologic factors behind the onset and development of non-communicable chronic inflammatory diseases. This review goes from the evidence in the formation of endogenous metabolites undergoing the mercapturate pathway to the methodologies for their assessment and their association with cancer and respiratory, neurologic and cardiometabolic diseases. PMID: 31018482 [PubMed]

Related Articles Epigenetic mapping of the Arabidopsis metabolome reveals mediators of the epigenotype-phenotype map. Genome Res. 2019 01;29(1):96-106 Authors: Kooke R, Morgado L, Becker F, van Eekelen H, Hazarika R, Zheng Q, de Vos RCH, Johannes F, Keurentjes JJB Abstract Identifying the sources of natural variation underlying metabolic differences between plants will enable a better understanding of plant metabolism and provide insights into the regulatory networks that govern plant growth and morphology. So far, however, the contribution of epigenetic variation to metabolic diversity has been largely ignored. In the present study, we utilized a panel of Arabidopsis thaliana epigenetic recombinant inbred lines (epiRILs) to assess the impact of epigenetic variation on the metabolic composition. Thirty epigenetic QTL (QTLepi) were detected, which partly overlap with QTLepi linked to growth and morphology. In an effort to identify causal candidate genes in the QTLepi regions and their putative trans-targets, we performed in silico small RNA and qPCR analyses. Differentially expressed genes were further studied by phenotypic and metabolic analyses of knockout mutants. Three genes were detected that recapitulated the detected QTLepi effects, providing evidence for epigenetic regulation in cis and in trans These results indicate that epigenetic mechanisms impact metabolic diversity, possibly via small RNAs, and thus aid in further disentangling the complex epigenotype-phenotype map. PMID: 30504416 [PubMed - indexed for MEDLINE]

22 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 2019/04/25PubMed 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.

22 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 2019/04/25PubMed 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.

25 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 2019/04/24PubMed 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.

25 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 2019/04/24PubMed 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.

21 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 2019/04/23PubMed 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.

21 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 2019/04/23PubMed 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.

Comparative metabolomics of temperature sensitive resistance to wheat streak mosaic virus (WSMV) in resistant and susceptible wheat cultivars. J Plant Physiol. 2019 Apr 12;237:30-42 Authors: Farahbakhsh F, Hamzehzarghani H, Massah A, Tortosa M, Yasayee M, Rodriguez VM Abstract In order to evaluate wheat resistance to wheat streak mosaic virus (WSMV) at low temperature and resistance breakdown at high temperature, metabolic profile of WSMV-resistant (R) and susceptible (S) wheat cultivars were analyzed. Metabolites were detected by UPLC-QTOF/MS in leaves of R and S plants challenged with WSMV at 20 °C and 32 °C, 24, 48 and 72 h post inoculation (hpi). WSMV and mock inoculated plants were used for discriminating the most significant metabolites and metabolic pathways affected at those temperatures. At 24 hpi/20 °C and 48 hpi/20 °C, the most important metabolites in R plants were coumarins, a limited number of lipids, and unknown compounds, while at 72 hpi/20 °C, in addition to coumarins, alkaloids and several amino acids were increased. Compared to 24 and 48 hpi, at 72hpi, in R plants most metabolic pathways were up-regulated at 20 °C. These resistance-related specific pathways included amino acid metabolism, lipid metabolism and alkaloids pathways. Also, several pathways were up-regulated at 32 °C.These combined heat stress and pathogen related pathways, included lipid metabolism and amino acid metabolism. Some carbohydrate metabolism pathways were considered as heat stress related pathways and could be associated with resistance breakdown. On the other hand, the increased expression of lipid compounds, especially 24 hpi at 32 °C in R plant, can be attributed to plant adaptation to combined stressors such as pathogen and high temperature. Increased susceptibility of R plants at 32 °C coincided with a down-regulated expression of components of signal transduction pathways or in a decreased level of metabolites related to this pathway, especially at a later time after infection, leading to decreased metabolite signaling. Decrease of signaling compounds under combined stress is a possible outcome of deactivating WSMV specific signaling networks leading to compatible response in R plants. The significance of these findings considering the recent increase of global temperature and the challenge of breakdown of temperature sensitive resistance to some plant viruses is discussed. PMID: 31005806 [PubMed - as supplied by publisher]