PubMed

Related Articles Analysis of sequential hair segments reflects changes in the metabolome across the trimesters of pregnancy. Sci Rep. 2018 01 08;8(1):36 Authors: Delplancke TDJ, de Seymour JV, Tong C, Sulek K, Xia Y, Zhang H, Han TL, Baker PN Abstract The hair metabolome has been recognized as a valuable source of information in pregnancy research, as it provides stable metabolite information that could assist with studying biomarkers or metabolic mechanisms of pregnancy and its complications. We tested the hypothesis that hair segments could be used to reflect a metabolite profile containing information from both endogenous and exogenous compounds accumulated during the nine months of pregnancy. Segments of hair samples corresponding to the trimesters were collected from 175 pregnant women in New Zealand. The hair samples were analysed using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. In healthy pregnancies, 56 hair metabolites were significantly different between the first and second trimesters, while 62 metabolites were different between the first and third trimesters (p < 0.05). Additionally, three metabolites in the second trimester hair samples were significantly different between healthy controls and women who delivered small-for-gestational-age infants (p < 0.05), and ten metabolites in third trimester hair were significantly different between healthy controls and women with gestational diabetes mellitus (p < 0.01). The findings from this pilot study provide improved insight into the changes of the hair metabolome during pregnancy, as well as highlight the potential of the maternal hair metabolome to differentiate pregnancy complications from healthy pregnancies. PMID: 29311683 [PubMed - indexed for MEDLINE]

Related Articles The Chemistry behind Health Effects of Whole Grains. Mol Nutr Food Res. 2017 07;61(7): Authors: Sang S, Landberg R PMID: 28670870 [PubMed - indexed for MEDLINE]

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 2018/11/21PubMed 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.

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/11/20PubMed 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 Metabolomics signature associated with circulating serum selenoprotein P levels. Endocrine. 2018 Nov 17;: Authors: di Giuseppe R, Koch M, Nöthlings U, Kastenmüller G, Artati A, Adamski J, Jacobs G, Lieb W Abstract PURPOSE: Selenoprotein P (SELENOP) has been previously related to various metabolic traits with partially conflicting results. The identification of SELENOP-associated metabolites, using an untargeted metabolomics approach, may provide novel biological insights relevant to disentangle the role of SELENOP in human health. METHODS: In this cross-sectional study, 572 serum metabolites were identified by comparing the obtained LC-MS/MS spectra with spectra stored in Metabolon's spectra library. Serum SELENOP levels were measured in 832 men and women using an ELISA kit. RESULTS: Circulating SELENOP levels were associated with 24 out of 572 metabolites after accounting for the number of independent dimensions in the metabolomics data, including inverse associations with alanine, glutamate, leucine, isoleucine and valine, an unknown compound X-12063, urate and the peptides gamma-glutamyl-leucine, and N-acetylcarnosine. Positive associations were observed between SELENOP and several lipid compounds. Of the identified metabolites, each standard deviation increase in the branched-chain amino acids (isoleucine, leucine, valine), alanine and gamma-glutamyl-leucine was related to higher odds of having T2DM [OR (95% CI): 1.96 (1.41-2.73); 1.62 (1.15-2.28); 1.94 (1.45-2.60), 1.57 (1.17-2.11), and 1.52 (1.13-2.05), respectively]. CONCLUSIONS: Higher serum SELENOP levels were associated with an overall healthy metabolomics profile, which may provide further insights into potential mechanisms of SELENOP-associated metabolic disorders. PMID: 30448992 [PubMed - as supplied by publisher]

Related Articles Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice. Gut. 2018 Nov 17;: Authors: Hendrikx T, Duan Y, Wang Y, Oh JH, Alexander LM, Huang W, Stärkel P, Ho SB, Gao B, Fiehn O, Emond P, Sokol H, van Pijkeren JP, Schnabl B Abstract OBJECTIVE: Antimicrobial C-type lectin regenerating islet-derived 3 gamma (REG3G) is suppressed in the small intestine during chronic ethanol feeding. Our aim was to determine the mechanism that underlies REG3G suppression during experimental alcoholic liver disease. DESIGN: Interleukin 22 (IL-22) regulates expression of REG3G. Therefore, we investigated the role of IL-22 in mice subjected to chronic-binge ethanol feeding (NIAAA model). RESULTS: In a mouse model of alcoholic liver disease, we found that type 3 innate lymphoid cells produce lower levels of IL-22. Reduced IL-22 production was the result of ethanol-induced dysbiosis and lower intestinal levels of indole-3-acetic acid (IAA), a microbiota-derived ligand of the aryl hydrocarbon receptor (AHR), which regulates expression of IL-22. Importantly, faecal levels of IAA were also found to be lower in patients with alcoholic hepatitis compared with healthy controls. Supplementation to restore intestinal levels of IAA protected mice from ethanol-induced steatohepatitis by inducing intestinal expression of IL-22 and REG3G, which prevented translocation of bacteria to liver. We engineered Lactobacillus reuteri to produce IL-22 (L. reuteri/IL-22) and fed them to mice along with the ethanol diet; these mice had reduced liver damage, inflammation and bacterial translocation to the liver compared with mice fed an isogenic control strain and upregulated expression of REG3G in intestine. However, L. reuteri/IL-22 did not reduce ethanol-induced liver disease in Reg3g-/- mice. CONCLUSION: Ethanol-associated dysbiosis reduces levels of IAA and activation of the AHR to decrease expression of IL-22 in the intestine, leading to reduced expression of REG3G; this results in bacterial translocation to the liver and steatohepatitis. Bacteria engineered to produce IL-22 induce expression of REG3G to reduce ethanol-induced steatohepatitis. PMID: 30448775 [PubMed - as supplied by publisher]

Related Articles Isotope Tracing Untargeted Metabolomics Reveals Macrophage Polarization-State-Specific Metabolic Coordination across Intracellular Compartments. iScience. 2018 Nov 02;9:298-313 Authors: Puchalska P, Huang X, Martin SE, Han X, Patti GJ, Crawford PA Abstract We apply stable isotope tracing, mass-spectrometry-based untargeted metabolomics, to reveal the biochemical space labeled by 13C-substrates in bone-marrow-derived macrophages. At the pathway level, classically (lipopolysaccharide [LPS]-polarized, M1) and alternatively (interleukin [IL]-4-polarized, M2) polarized macrophages were 13C-labeled with surprising concordance. Total pools of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), an intermediate in the hexosamine biosynthetic pathway, were equally abundant in LPS- and IL-4-polarized macrophages. Informatic scrutiny of 13C-isotopologues revealed that LPS-polarized macrophages leverage the pentose phosphate pathway to generate UDP-GlcNAc, whereas IL-4-polarized macrophages rely on intact glucose and mitochondrial metabolism of glucose carbon. Labeling from [13C]glucose is competed by unlabeled fatty acids and acetoacetate, underscoring the broad roles for substrate metabolism beyond energy conversion. Finally, the LPS-polarized macrophage metabolite itaconate is imported into IL-4-polarized macrophages, in which it reprograms [13C]glucose metabolism. Thus, use of fully unsupervised isotope tracing metabolomics in macrophages reveals polarization-state-specific metabolic pathway connectivity, substrate competition, and metabolite allocation among cellular compartments. PMID: 30448730 [PubMed - as supplied by publisher]

Related Articles The impact of chronic environmental metal and benzene exposure on human urinary metabolome among Chinese children and the elderly population. Ecotoxicol Environ Saf. 2018 Nov 15;169:232-239 Authors: Wang Z, Xu X, He B, Guo J, Zhao B, Zhang Y, Zhou Z, Zhou X, Zhang R, Abliz Z Abstract The health effects of metals and benzene exposure have been extensively investigated; however, information on the impact of chronic environmental metal and benzene exposure on human urinary metabolome is limited. In this study, a total of 566 participants, including 352 elderly and 214 children, were split into the "exposed" and "control" groups. The urine samples of all the participants were collected and stored at - 80 °C until analysis. The urinary levels of 17 metals and S-phenylmercapturic acid (S-PMA) were determined by the ICP-MS and LC-MS/MS methods to comprehensively assess the personal metal and benzene exposure levels, respectively. Then, the individual levels of metal and benzene exposure were correlated to the metabolic consequences of ambient pollutant exposure, which were previously observed in our metabolomics study. As a result, multiple metals, including Cd, Co, Cr, Cu, Fe, Hg, Li, Mo, Ni, Pb, Se, and Zn, exhibited a significant linear dose-dependent association with one or more urinary metabolites, including two amino acids (pyroglutamic acid and 3-methylhistidine), three organic acids (azelaic acid, decenedioic acid, and hydroxytetradecanedioic acid), ten medium-chainacylcarnitines (heptenedioylcarnitine, octenedioylcarnitine, nonenedioylcarnitine, decenedioylglucuronide, 3-hydroxydecanoylcarnitine, dodecanedioylcarnitine, nonanoylcarnitine, decadienylcarnitine, hydroxydodecenoylcarnitine, dodecadienylcarnitine, and dodecenoylcarnitine), and one glucuronide conjugate (decenedioylglucuronide). These observations indicate that the increased environmental metal exposure has caused various oxidative stress-related effects, including the depletion of antioxidants, accelerated muscle proteolysis, elevated activity of UGTs, increased lipid peroxidation, and the disorder of mitochondrial lipid metabolism among exposed children and the elderly. The current study provides new insights into the biological effects induced by metal exposure in the environment. PMID: 30448706 [PubMed - as supplied by publisher]

Related Articles Non-targeted metabolomic analysis on multidrug resistance hepatocellular carcinoma cell and reversal effect of annonaceous acetogenins. J Pharm Biomed Anal. 2018 Oct 25;164:489-495 Authors: Ma C, Yan X, Yin G, Wang Y, Hu S, Xia W, Chen Y, Liu X, Chen J, Li X Abstract Multidrug-resistance (MDR) has been shown to play a critical role in the development of many diseases. In this study, we used metabolomic method to evaluate the MDR in hepatocellular carcinoma, and investigate regulatory of annonaceous acetogenins on MDR of hepatocellular carcinoma. Multivariate statistical analysis revealed that the MDR of SMMC 7721 together with changes in glutathione metabolism, arginine and proline metabolism, sphingolipid metabolism. Annonaceous acetogenins impact these metabolism pathways. Metabolic pathway analysis coupled with stoichiometry analysis can be an effective tool to understand MDR mechanism and to potentially find new MDR reversal agents. PMID: 30448539 [PubMed - as supplied by publisher]

Related Articles Discovering significantly different metabolites between Han and Uygur two racial groups using urinary metabolomics in Xinjiang, China. J Pharm Biomed Anal. 2018 Nov 11;164:481-488 Authors: Shi H, Yuan J, Zhang Y, Feng S, Wang J Abstract The main object of the study was to discover the associated significantly different metabolites between Han and Uygur, two main racial groups in Xinjiang, China with urinary metabolomics. Urine samples from 96 Han and 96 Uygur were analyzed using gas chromatography coupled to mass spectrometry (GCMS). Multivariate analysis was used to investigate the effect of race, age and gender on the urinary metabolomic profiles. Totally eight metabolites are identified contributed to the discrimination between Han and Uygur, including phenylacetylglutamine, myoinositol, d-galactose, ribonolactone, octadecanoic acid, galactitol, threonic acid and succinic acid. The metabolic pathways of them are mainly involved in carbohydrate, TCA cycle, fatty acid and mammalian gut microbial-related metabolism. Importantly, three metabolites, being used as biomarkers in clinic, are also differentially expressed in urine samples of two races. It suggests that the race effect should be critically considered prior to make diagnostic result in multi-race coexisted areas to decrease the false positive rate caused by above biomarkers. Moreover, the results show that the age-period and the gender also affect the urinary metabolomics profiles, but with different levels compared to race. We hope that the work can provide some help for developing novel diagnostic tests, understanding the mechanism of disease, designing clinical trials and refining precision medicine in multi-race coexisted areas. PMID: 30448538 [PubMed - as supplied by publisher]

31 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 2018/11/18PubMed 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.

Development, characterization and comparisons of targeted and non-targeted metabolomics methods. PLoS One. 2018;13(11):e0207082 Authors: Ribbenstedt A, Ziarrusta H, Benskin JP Abstract The potential of a metabolomics method to detect statistically significant perturbations in the metabolome of an organism is enhanced by excellent analytical precision, unequivocal identification, and broad metabolomic coverage. While the former two metrics are usually associated with targeted metabolomics and the latter with non-targeted metabolomics, a systematic comparison of the performance of both approaches has not yet been carried out. The present work reports on the development and performance evaluation of separate targeted and non-targeted metabolomics methods. The targeted approach facilitated determination of 181 metabolites (quantitative analysis of 18 amino acids, 11 biogenic amines, 5 neurotransmitters, 5 nucleobases and semi-quantitative analysis of 50 carnitines, 83 phosphatidylcholines, and 9 sphingomyelins) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and flow injection-tandem mass spectrometry (FI-MS/MS). Method accuracy and/or precision were assessed using replicate samples of NIST SRM1950 as well as fish liver and brain tissue from Gilthead Bream (Sparus aurata). The non-target approach involved UPLC-high resolution (Orbitrap) mass spectrometry (UPLC-HRMS). Testing of ionization mode and stationary phase revealed that a combination of positive electrospray ionization and HILIC chromatography produced the largest number of chromatographic features during non-target analysis. Furthermore, an evaluation of 4 different sequence drift correction algorithms, and combinations thereof, revealed that batchCorr produced the best precision in almost every test. However, even following correction of non-target data for signal drift, the precision of targeted data was better, confirming our existing assumptions about the strengths of targeted metabolomics. Finally, the accuracy of the online MS2-library mzCloud was evaluated using reference standards for 38 different metabolites. This is among the few studies that have systematically evaluated the performance of targeted and non-targeted metabolomics and provides new insight into the advantages and disadvantages of each approach. PMID: 30439966 [PubMed - in process]

Role of Trichoderma arundinaceum tri10 in regulation of terpene biosynthetic genes and in control of metabolic flux. Fungal Genet Biol. 2018 Nov 12;: Authors: Lindo L, McCormick SP, Cardoza RE, Kim HS, Brown DW, Alexander NJ, Proctor RH, Gutiérrez S Abstract Production of trichothecene toxins occurs in phylogenetically diverse fungi with different lifestyles. In these fungi, most homologs of the trichothecene biosynthetic gene cluster include the transcription factor genes tri6 and tri10. Analyses of phytopathogenic species of Fusarium indicate that the TRI6 and TRI10 proteins positively regulate genes required for synthesis of trichothecenes as well as farnesyl diphosphate (FPP), a precursor of the trichothecene and other terpenoids (e.g., ergosterol). However, the apparent absence of tri6 and tri10 in some trichothecene-producing fungi, and the presence of multiple paralogs of the genes in others suggest considerable variability in genetic regulation of trichothecene synthesis. To begin to investigate this variability, we functionally characterized tri10 in the saprotrophic fungus Trichoderma arundinaceum. We found that TRI10 is required for wild-type expression of tri genes and trichothecene production during the first 12 h of growth of T. arundinaceum. Comparison of the effect of tri10 deletion in T. arundinaceum and Fusarium species has provided evidence for similarities in the genetic regulation of trichothecene biosynthesis in these two fungi with different lifestyles. In contrast to trichothecenes, tri10 deletion increased production of ergosterol and the polyketide-derived metabolites aspinolides, which is more likely caused by an increase in the intracellular pool of FPP resulting from loss of trichothecene production. Furthermore, although it is unclear how TRI10 effects polyketide production, one possibility is that it does so by rechanneling terpene precursors. PMID: 30439446 [PubMed - as supplied by publisher]

Development of a Pseudomonas syringae - Arabidopsis suspension cell infection system for investigating host metabolite-dependent regulation of type III secretion and pattern-triggered immunity. Mol Plant Microbe Interact. 2018 Nov 15;: Authors: Yan Q, Rogan C, Anderson JC Abstract The importance of Pattern-Triggered Immunity (PTI) in plant defense has been clearly established through genetic studies of mutants lacking functional pattern recognition receptors (PRRs) and signaling components downstream of PRR activation. Despite extensive knowledge of PRR-mediated signaling responses to Pathogen-Associated Molecular Patterns (PAMPs), little is known about which of these responses, if any, are directly responsible for limiting bacterial growth. In this work we established a protocol for co-culturing the bacterial pathogen Pseudomonas syringae pv tomato DC3000 and Arabidopsis suspensions cells. The system closely mirrors infection processes that occur in leaves, with bacteria relying on the type III secretion system (T3SS) for maximal growth and PAMP-induced plant defenses effectively limiting bacterial growth. To demonstrate the utility of this system, we investigated the molecular basis of PAMP-induced growth inhibition and discovered that T3SS-associated genes are inhibited when DC3000 is co-cultured with PAMP-treated plant suspension cells. To determine the underlying mechanism of decreased T3SS gene expression, we performed metabolomics and biochemical analyses of suspension cell exudates and identified fourteen metabolites that significantly increased or decreased following PAMP treatment. Citric acid, a known inducer of T3SS gene expression in DC3000, was among several organic acids decreased in exudates from PAMP-treated plant cells. Exogenous addition of citric acid increased T3SS gene expression and partially recovered growth of DC3000 in the presence of PAMP-treated cells, indicating that a portion of PAMP-induced defense in this system is decreased extracellular release of this metabolite. We envision that the well-defined infection conditions of this co-culture system will be valuable for quantitative studies of type III effector delivery by P. syringae. Furthermore, this system provides a unique "top-down" approach to unravel the molecular basis of PTI against P. syringae. PMID: 30431399 [PubMed - as supplied by publisher]

GLUT6 is a lysosomal transporter that is regulated by inflammatory stimuli and modulates glycolysis in macrophages. FEBS Lett. 2018 Nov 15;: Authors: Maedera S, Mizuno T, Ishiguro H, Ito T, Soga T, Kusuhara H Abstract The solute carrier family is an important protein class governing compound transport across membranes. However, some of its members remain functionally unidentified. We analyzed ChIP-seq data for the NF-κB family transcription factor RelA and identified GLUT6 as a functionally uncharacterized transporter that putatively works in inflammatory responses. Inflammatory stimuli increase GLUT6 expression level, although GLUT6-knockout mice exhibit a subtle phenotype to lipopolysaccharide administration. Metabolomics and in vitro analyses show that GLUT6 functions as a glycolysis modulator in inflammatory macrophages. GLUT6 does not mediate glucose uptake and is localized on lysosomal membranes. We conclude that GLUT6 is a lysosomal transporter that is regulated by inflammatory stimuli and modulates inflammatory responses by affecting the metabolic shift in macrophages. This article is protected by copyright. All rights reserved. PMID: 30431159 [PubMed - as supplied by publisher]

UPLC/Q‑TOF‑MS based plasma metabolomics and clinical characteristics of polycystic ovarian syndrome. Mol Med Rep. 2018 Nov 12;: Authors: Fan X, Jiang J, Huang Z, Gong J, Wang Y, Xue W, Deng Y, Wang Y, Zheng T, Sun A, Luo G Abstract The present study aimed to develop novel diagnostic methods for polycystic ovarian syndrome (PCOS) by screening and identifying specific PCOS‑associated metabolic markers using plasma metabolomics. Ultra‑performance liquid chromatography/quadrapole‑time of flight‑mass spectrometry was adopted to establish the plasma metabolic fingerprint of 49 patients and 50 normal controls, in order to screen the potential metabolic markers. In addition, these markers were integrated with the clinical indexes, followed by focused analysis to obtain diagnostic markers. The present results demonstrated that not only was the concentration of palmitoyl sphingomyelin in plasma of patients with PCOS significantly increased; however, a statistically significant difference between the two PCOS subgroups was additionally demonstrated. At the same time, the concentrations of cyclic guanosine monophosphate (cGMP) and dehydroepiandrosterone sulphate in the plasma of patients of the subgroup 1 were significantly elevated. These markers were additionally integrated with the clinical index number of follicles in the left ovary and high‑density lipoprotein (HDL‑C), followed by receiver operating characteristic curve analysis, which demonstrated a diagnostic accuracy of ~90% in the control and the two subgroups. The integrated marker system consisting of palmitoyl sphingomyelin, cGMP and androsterone sulfate, as well as the number of left follicles and HDL‑C may be used for the accurate diagnosis and classification of PCOS. These results confirmed that the abnormalities in hormone metabolism and lipid metabolism disorder were primarily involved in the onset of PCOS. PMID: 30431132 [PubMed - as supplied by publisher]

Application of metabolomics part II: Focus on fatty acids and their metabolites in healthy adults. Int J Mol Med. 2018 Nov 14;: Authors: Tsoukalas D, Alegakis AK, Fragkiadaki P, Papakonstantinou E, Tsilimidos G, Geraci F, Sarandi E, Nikitovic D, Spandidos DA, Tsatsakis A Abstract Fatty acids (FAs) play critical roles in health and disease. The detection of FA imbalances through metabolomics can provide an overview of an individual's health status, particularly as regards chronic inflammatory disorders. In this study, we aimed to establish sensitive reference value ranges for targeted plasma FAs in a well‑defined population of healthy adults. Plasma samples were collected from 159 participants admitted as outpatients. A total of 24 FAs were analyzed using gas chromatography‑mass spectrometry, and physiological values and 95% reference intervals were calculated using an approximate method of analysis. The differences among the age groups for the relative levels of stearic acid (P=0.005), the omega‑6/omega‑3 ratio (P=0.027), the arachidonic acid/eicosapentaenoic acid ratio (P<0.001) and the linoleic acid‑produced dihomo‑gamma‑linolenic acid (P=0.046) were statistically significant. The majority of relative FA levels were higher in males than in females. The levels of myristic acid (P=0.0170) and docosahexaenoic acid (P=0.033) were significantly different between the sexes. The reference values for the FAs examined in this study represent a baseline for further studies examining the reproducibility of this methodology and sensitivities for nutrient deficiency detection and investigating the biochemical background of pathological conditions. The application of these values to clinical practice will allow for the discrimination between health and disease and contribute to early prevention and treatment. PMID: 30431095 [PubMed - as supplied by publisher]

Related Articles The challenge and potential of photosynthesis: unique considerations for metabolic flux measurements in photosynthetic microorganisms. Biotechnol Lett. 2018 Nov 14;: Authors: Sake CL, Metcalf AJ, Boyle NR Abstract Photosynthetic microorganisms have the potential for sustainable production of chemical feedstocks and products but have had limited success due to a lack of tools and deeper understanding of metabolic pathway regulation. The application of instationary metabolic flux analysis (INST-MFA) to photosynthetic microorganisms has allowed researchers to quantify fluxes and identify bottlenecks and metabolic inefficiencies to improve strain performance or gain insight into cellular physiology. Additionally, flux measurements can also highlight deviations between measured and predicted fluxes, revealing weaknesses in metabolic models and highlighting areas where a lack of understanding still exists. In this review, we outline the experimental steps necessary to successfully perform photosynthetic flux experiments and analysis. We also discuss the challenges unique to photosynthetic microorganisms and how to account for them, including: light supply, quenching, concentration, extraction, analysis, and flux calculation. We hope that this will enable a larger number of researchers to successfully apply isotope assisted metabolic flux analysis (13C-MFA) to their favorite photosynthetic organism. PMID: 30430405 [PubMed - as supplied by publisher]

Related Articles Combined transcriptomics-metabolomics profiling of the heat shock response in the hyperthermophilic archaeon Pyrococcus furiosus. Extremophiles. 2018 Nov 14;: Authors: Esteves AM, Graça G, Peyriga L, Torcato IM, Borges N, Portais JC, Santos H Abstract Pyrococcus furiosus is a remarkable archaeon able to grow at temperatures around 100 °C. To gain insight into how this model hyperthermophile copes with heat stress, we compared transcriptomic and metabolomic data of cells subjected to a temperature shift from 90 °C to 97 °C. In this study, we used RNA-sequencing to characterize the global variation in gene expression levels, while nuclear magnetic resonance (NMR) and targeted ion exchange liquid chromatography-mass spectrometry (LC-MS) were used to determine changes in metabolite levels. Of the 552 differentially expressed genes in response to heat shock conditions, 257 were upregulated and 295 were downregulated. In particular, there was a significant downregulation of genes for synthesis and transport of amino acids. At the metabolite level, 37 compounds were quantified. The level of di-myo-inositol phosphate, a canonical heat stress solute among marine hyperthermophiles, increased considerably (5.4-fold) at elevated temperature. Also, the levels of mannosylglycerate, UDP-N-acetylglucosamine (UDPGlcNac) and UDP-N-acetylgalactosamine were enhanced. The increase in the pool of UDPGlcNac was concurrent with an increase in the transcript levels of the respective biosynthetic genes. This work provides the first metabolomic analysis of the heat shock response of a hyperthermophile. PMID: 30430272 [PubMed - as supplied by publisher]

Related Articles PGE2 Augments Inflammasome Activation and M1 Polarization in Macrophages Infected With Salmonella Typhimurium and Yersinia enterocolitica. Front Microbiol. 2018;9:2447 Authors: Sheppe AEF, Kummari E, Walker A, Richards A, Hui WW, Lee JH, Mangum L, Borazjani A, Ross MK, Edelmann MJ Abstract Eicosanoids are cellular metabolites, which shape the immune response, including inflammatory processes in macrophages. The effects of these lipid mediators on inflammation and bacterial pathogenesis are not clearly understood. Certain eicosanoids are suspected to act as molecular sensors for the recruitment of neutrophils, while others regulate bacterial uptake. In this study, gene expression analyses indicated that genes involved in eicosanoid biosynthesis including COX-1, COX-2, DAGL, and PLA-2 are differentially regulated in THP-1 human macrophages infected with Salmonella enterica Typhimurium or Yersinia enterocolitica. By using targeted metabolomics approach, we found that the eicosanoid precursor, arachidonic acid (AA) as well as its derivatives, including prostaglandins (PGs) PGF2α or PGE2/PGD2, and thromboxane TxB2, are rapidly secreted from macrophages infected with these Gram-negative pathogenic bacteria. The magnitude of eicosanoid biosynthesis in infected host cells depends on the presence of virulence factors of Y. enterocolitica and S. Typhimurium strains, albeit in an opposite way in Y. enterocolitica compared to S. Typhimurium infection. Trials with combinations of EP2/EP4 PGE2 receptor agonists and antagonists suggest that PGE2 signaling in these infection models works primarily through the EP4 receptor. Downstream of EP4 activation, PGE2 enhances inflammasome activation and represses M2 macrophage polarization while inducing key M1-type markers. PGE2 also led to a decreased numbers of Y. enterocolitica within macrophages. To summarize, PGE2 is a potent autocrine/paracrine activator of inflammation during infection in Gram-negative bacteria, and it affects macrophage polarization, likely controlling bacterial clearance by macrophages. PMID: 30429830 [PubMed]