PubMed

Related Articles Discovery of pentangular polyphenols hexaricins A-C from marine Streptosporangium sp. CGMCC 4.7309 by genome mining. Appl Microbiol Biotechnol. 2016 May;100(9):4189-99 Authors: Tian J, Chen H, Guo Z, Liu N, Li J, Huang Y, Xiang W, Chen Y Abstract Many novel microbial nature products were discovered from Actinobacteria by genome mining methods. However, only a few number of genome mining works were carried out in rare actinomycetes. An important reason precluding the genome mining efforts in rare actinomycetes is that most of them are recalcitrant to genetic manipulation. Herein, we chose the rare marine actinomycete Streptosporangium sp. CGMCC 4.7309 to explore its secondary metabolite diversity by genome mining. The genetic manipulation method has never been established for Streptosporangium strains. At first, we set up the genetic system of Streptosporangium sp. CGMCC 4.7309 unprecedentedly. The draft genome sequencing of Streptosporangium sp. CGMCC 4.7309 revealed that it contains more than 20 cryptic secondary metabolite biosynthetic clusters. A type II polyketide synthases-containing cluster (the hex cluster) was predicted to encode compounds with a pentangular polyphenol scaffold by in silico analysis. The products of the hex cluster were uncovered by comparing the metabolic profile of Streptosporangium sp. CGMCC 4.7309 with that of the hex30 inactivated mutant, in which a key ketoreductase gene was disrupted. Finally, three pentangular polyphenols were isolated and named as hexaricins A (1), B (2), and C (3). The inconsistency of the stereochemistry of C-15 in hexaricins A, B, and C indicates a branch point in their biosynthesis. Finally, the biosynthetic pathway of the hexaricins was proposed based on bioinformatics analysis. PMID: 26754814 [PubMed - indexed for MEDLINE]

Related Articles Methionine Metabolism Alters Oxidative Stress Resistance via the Pentose Phosphate Pathway. Antioxid Redox Signal. 2016 Apr 01;24(10):543-7 Authors: Campbell K, Vowinckel J, Keller MA, Ralser M Abstract Nutrient uptake and metabolism have a significant impact on the way cells respond to stress. The amino acid methionine is, in particular, a key player in the oxidative stress response, and acting as a reactive oxygen species scavenger, methionine is implicated in caloric restriction phenotypes and aging. We here provide evidence that some effects of methionine in stress situations are indirect and caused by altered activity of the nicotinamide adenine dinucleotide phosphate (NADPH) producing oxidative part of the pentose phosphate pathway (PPP). In Saccharomyces cerevisiae, both methionine prototrophic (MET15) and auxotrophic (met15Δ) cells supplemented with methionine showed an increase in PPP metabolite concentrations downstream of the NADPH producing enzyme, 6-phosphogluconate dehydrogenase. Proteomics revealed this enzyme to also increase in expression compared to methionine self-synthesizing cells. Oxidant tolerance was increased in cells preincubated with methionine; however, this effect was abolished when flux through the oxidative PPP was prevented by deletion of its rate limiting enzyme, ZWF1. Stress resistance phenotypes that follow methionine supplementation hence involve the oxidative PPP. Effects of methionine on oxidative metabolism, stress signaling, and aging have thus to be seen in the context of an altered activity of this NADP reducing pathway. PMID: 26596469 [PubMed - indexed for MEDLINE]

Related Articles Lipidomic and transcriptomic analyses of Chlamydomonas reinhardtii under heat stress unveil a direct route for the conversion of membrane lipids into storage lipids. Plant Cell Environ. 2016 Apr;39(4):834-47 Authors: Légeret B, Schulz-Raffelt M, Nguyen HM, Auroy P, Beisson F, Peltier G, Blanc G, Li-Beisson Y Abstract Studying how photosynthetic cells modify membrane lipids in response to heat stress is important to understand how plants and microalgae adapt to daily fluctuations in temperature and to investigate new lipid pathways. Here, we investigate changes occurring in lipid molecular species and lipid metabolism genes during early response to heat stress in the model photosynthetic microorganism Chlamydomonas reinhardtii. Lipid molecular species analyses revealed that, after 60 min at 42 °C, a strong decrease in specific polyunsaturated membrane lipids was observed together with an increase in polyunsaturated triacylglycerols (TAGs) and diacylglycerols (DAGs). The fact that decrease in the major chloroplastic monogalactosyldiacylglycerol sn1-18:3/sn2-16:4 was mirrored by an accumulation of DAG sn1-18:3/sn2-16:4 and TAG sn1-18:3/sn2-16:4/sn3-18:3 indicated that newly accumulated TAGs were formed via direct conversion of monogalactosyldiacylglycerols to DAGs then TAGs. Lipidomic analyses showed that the third fatty acid of a TAG likely originated from a phosphatidylethanolamine or a diacylglyceryl-O-4'-(N,N,N,-trimethyl)-homoserine betaine lipid species. Candidate genes for this TAG synthesis pathway were provided through comparative transcriptomic analysis and included a phospholipase A2 homolog and the DAG acyltransferase DGTT1. This study gives insights into the molecular events underlying changes in membrane lipids during heat stress and reveals an alternative route for TAG synthesis. PMID: 26477535 [PubMed - indexed for MEDLINE]

Related Articles Guard cell-specific upregulation of sucrose synthase 3 reveals that the role of sucrose in stomatal function is primarily energetic. New Phytol. 2016 Mar;209(4):1470-83 Authors: Daloso DM, Williams TC, Antunes WC, Pinheiro DP, Müller C, Loureiro ME, Fernie AR Abstract Isoform 3 of sucrose synthase (SUS3) is highly expressed in guard cells; however, the precise function of SUS3 in this cell type remains to be elucidated. Here, we characterized transgenic Nicotiana tabacum plants overexpressing SUS3 under the control of the stomatal-specific KST1 promoter, and investigated the changes in guard cell metabolism during the dark to light transition. Guard cell-specific SUS3 overexpression led to increased SUS activity, stomatal aperture, stomatal conductance, transpiration rate, net photosynthetic rate and growth. Although only minor changes were observed in the metabolite profile in whole leaves, an increased fructose level and decreased organic acid levels and sucrose to fructose ratio were observed in guard cells of transgenic lines. Furthermore, guard cell sucrose content was lower during light-induced stomatal opening. In a complementary approach, we incubated guard cell-enriched epidermal fragments in (13) C-NaHCO3 and followed the redistribution of label during dark to light transitions; this revealed increased labeling in metabolites of, or associated with, the tricarboxylic acid cycle. The results suggest that sucrose breakdown is a mechanism to provide substrate for the provision of organic acids for respiration, and imply that manipulation of guard cell metabolism may represent an effective strategy for plant growth improvement. PMID: 26467445 [PubMed - indexed for MEDLINE]

Related Articles Analysis of Urine, Oral fluid and Fingerprints by Liquid Extraction Surface Analysis Coupled to High Resolution MS and MS/MS - Opportunities for Forensic and Biomedical Science. Anal Methods. 2016 Apr 28;2016(16):3373-3382 Authors: Bailey M, Randall EC, Costa C, Salter TL, Race AM, de Puit M, Koeberg M, Baumert M, Bunch J Abstract Liquid Extraction Surface Analysis (LESA) is a new, high throughput tool for ambient mass spectrometry. A solvent droplet is deposited from a pipette tip onto a surface and maintains contact with both the surface and the pipette tip for a few seconds before being re-aspirated. The technique is particularly suited to the analysis of trace materials on surfaces due to its high sensitivity and low volume of sample removal. In this work, we assess the suitability of LESA for obtaining detailed chemical profiles of fingerprints, oral fluid and urine, which may be used in future for rapid medical diagnostics or metabolomics studies. We further show how LESA can be used to detect illicit drugs and their metabolites in urine, oral fluid and fingerprints. This makes LESA a potentially useful tool in the growing field of fingerprint chemical analysis, which is relevant not only to forensics but also to medical diagnostics. Finally, we show how LESA can be used to detect the explosive material RDX in contaminated artificial fingermarks. PMID: 27990179 [PubMed - in process]

Related Articles Enhanced production of 2,3-butanediol by engineered Saccharomyces cerevisiae through fine-tuning of pyruvate decarboxylase and NADH oxidase activities. Biotechnol Biofuels. 2016;9:265 Authors: Kim JW, Kim J, Seo SO, Kim KH, Jin YS, Seo JH Abstract BACKGROUND: 2,3-Butanediol (2,3-BD) is a promising compound for various applications in chemical, cosmetic, and agricultural industries. Pyruvate decarboxylase (Pdc)-deficient Saccharomyces cerevisiae is an attractive host strain for producing 2,3-BD because a large amount of pyruvate could be shunted to 2,3-BD production instead of ethanol synthesis. However, 2,3-BD yield, productivity, and titer by engineered yeast were inferior to native bacterial producers because of the following metabolic limitations. First, the Pdc-deficient yeast showed growth defect due to a shortage of C2-compounds. Second, redox imbalance during the 2,3-BD production led to glycerol formation that lowered the yield. RESULTS: To overcome these problems, the expression levels of Pdc from a Crabtree-negative yeast were optimized in S. cerevisiae. Specifically, Candida tropicalis PDC1 (CtPDC1) was used to minimize the production of ethanol but maximize cell growth and 2,3-BD productivity. As a result, productivity of the BD5_G1CtPDC1 strain expressing an optimal level of Pdc was 2.3 folds higher than that of the control strain in flask cultivation. Through a fed-batch fermentation, 121.8 g/L 2,3-BD was produced in 80 h. NADH oxidase from Lactococcus lactis (noxE) was additionally expressed in the engineered yeast with an optimal activity of Pdc. The fed-batch fermentation with the optimized 2-stage aeration control led to production of 154.3 g/L 2,3-BD in 78 h. The overall yield of 2,3-BD was 0.404 g 2,3-BD/g glucose which corresponds to 80.7% of theoretical yield. CONCLUSIONS: A massive metabolic shift in the engineered S. cerevisiae (BD5_G1CtPDC1_nox) expressing NADH oxidase was observed, suggesting that redox imbalance was a major bottleneck for efficient production of 2,3-BD by engineered yeast. Maximum 2,3-BD titer in this study was close to the highest among the reported microbial production studies. The results demonstrate that resolving both C2-compound limitation and redox imbalance is critical to increase 2,3-BD production in the Pdc-deficient S. cerevisiae. Our strategy to express fine-tuned PDC and noxE could be applicable not only to 2,3-BD production, but also other chemical production systems using Pdc-deficient S. cerevisiae. PMID: 27990176 [PubMed - in process]

Related Articles Cysteinyl Leukotrienes Pathway Genes, Atopic Asthma and Drug Response: From Population Isolates to Large Genome-Wide Association Studies. Front Pharmacol. 2016;7:299 Authors: Thompson MD, Capra V, Clunes MT, Rovati GE, Stankova J, Maj MC, Duffy DL Abstract Genetic variants associated with asthma pathogenesis and altered response to drug therapy are discussed. Many studies implicate polymorphisms in genes encoding the enzymes responsible for leukotriene synthesis and intracellular signaling through activation of seven transmembrane domain receptors, such as the cysteinyl leukotriene 1 (CYSLTR1) and 2 (CYSLTR2) receptors. The leukotrienes are polyunsaturated lipoxygenated eicosatetraenoic acids that exhibit a wide range of pharmacological and physiological actions. Of the three enzymes involved in the formation of the leukotrienes, arachidonate 5 lipoxygenase 5 (ALOX5), leukotriene C4 synthase (LTC4S), and leukotriene hydrolase (LTA4H) are all polymorphic. These polymorphisms often result in variable production of the CysLTs (LTC4, LTD4, and LTE4) and LTB4. Variable number tandem repeat sequences located in the Sp1-binding motif within the promotor region of the ALOX5 gene are associated with leukotriene burden and bronchoconstriction independent of asthma risk. A 444A > C SNP polymorphism in the LTC4S gene, encoding an enzyme required for the formation of a glutathione adduct at the C-6 position of the arachidonic acid backbone, is associated with severe asthma and altered response to the CYSLTR1 receptor antagonist zafirlukast. Genetic variability in the CysLT pathway may contribute additively or synergistically to altered drug responses. The 601 A > G variant of the CYSLTR2 gene, encoding the Met201Val CYSLTR2 receptor variant, is associated with atopic asthma in the general European population, where it is present at a frequency of ∼2.6%. The variant was originally found in the founder population of Tristan da Cunha, a remote island in the South Atlantic, in which the prevalence of atopy is approximately 45% and the prevalence of asthma is 36%. In vitro work showed that the atopy-associated Met201Val variant was inactivating with respect to ligand binding, Ca(2+) flux and inositol phosphate generation. In addition, the CYSLTR1 gene, located at Xq13-21.1, has been associated with atopic asthma. The activating Gly300Ser CYSLTR1 variant is discussed. In addition to genetic loci, risk for asthma may be influenced by environmental factors such as smoking. The contribution of CysLT pathway gene sequence variants to atopic asthma is discussed in the context of other genes and environmental influences known to influence asthma. PMID: 27990118 [PubMed - in process]

Related Articles Engineering a functional 1-deoxy-D-xylulose 5-phosphate (DXP) pathway in Saccharomyces cerevisiae. Metab Eng. 2016 Oct 27;: Authors: Kirby J, Dietzel KL, Wichmann G, Chan R, Antipov E, Moss N, Baidoo EE, Jackson P, Gaucher SP, Gottlieb S, LaBarge J, Mahatdejkul T, Hawkins KM, Muley S, Newman JD, Liu P, Keasling JD, Zhao L Abstract Isoprenoids are used in many commercial applications and much work has gone into engineering microbial hosts for their production. Isoprenoids are produced either from acetyl-CoA via the mevalonate pathway or from pyruvate and glyceraldehyde 3-phosphate via the 1-deoxy-D-xylulose 5-phosphate (DXP) pathway. Saccharomyces cerevisiae exclusively utilizes the mevalonate pathway to synthesize native isoprenoids and in fact the alternative DXP pathway has never been found or successfully reconstructed in the eukaryotic cytosol. There are, however, several advantages to isoprenoid synthesis via the DXP pathway, such as a higher theoretical yield, and it has long been a goal to transplant the pathway into yeast. In this work, we investigate and address barriers to DXP pathway functionality in S. cerevisiae using a combination of synthetic biology, biochemistry and metabolomics. We report, for the first time, functional expression of the DXP pathway in S. cerevisiae. Under low aeration conditions, an engineered strain relying solely on the DXP pathway for isoprenoid biosynthesis achieved an endpoint biomass 80% of that of the same strain using the mevalonate pathway. PMID: 27989805 [PubMed - as supplied by publisher]

Related Articles A serum metabolomics-based profile in low bone mineral density postmenopausal women. Bone. 2016 Oct 29;: Authors: Miyamoto T, Hirayama A, Sato Y, Koboyashi T, Katsuyama E, Kanagawa H, Miyamoto H, Mori T, Yoshida S, Fujie A, Morita M, Watanabe R, Tando T, Miyamoto K, Tsuji T, Funayama A, Nakamura M, Matsumoto M, Soga T, Tomita M, Toyama Y Abstract Osteoporosis is characterized as a metabolic disorder of bone tissue, and various metabolic markers are now available to support its diagnosis and evaluate treatment effects. Substances produced as end products of metabolomic activities are the correlated factors to the biological or metabolic status, and thus, metabolites are considered highly sensitive markers of particular pathological states, including osteoporosis. Here we undertook comprehensive serum metabolomics analysis in postmenopausal women with or without low bone mineral density (low BMD vs controls) for the first time using capillary electrophoresis/mass spectrometry. Among the metabolites tested, 57 were detected in sera. Levels of hydroxyproline, Gly-Gly and cystine, differed significantly between groups, with Gly-Gly and cystine significantly lower in the low BMD group and hydroxyproline, a reported marker of osteoporosis, significantly higher. Levels of TRACP5b, a bone resorption marker, were significantly higher in the low BMD group, supporting the study's validity. Taken together, our findings represent novel metabolomic profiling in low BMD in postmenopausal women. PMID: 27989648 [PubMed - as supplied by publisher]

Related Articles Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy. Am J Hum Genet. 2016 Dec 10;: Authors: Ait-El-Mkadem S, Dayem-Quere M, Gusic M, Chaussenot A, Bannwarth S, François B, Genin EC, Fragaki K, Volker-Touw CL, Vasnier C, Serre V, van Gassen KL, Lespinasse F, Richter S, Eisenhofer G, Rouzier C, Mochel F, De Saint-Martin A, Abi Warde MT, de Sain-van der Velde MG, Jans JJ, Amiel J, Avsec Z, Mertes C, Haack TB, Strom T, Meitinger T, Bonnen PE, Taylor RW, Gagneur J, van Hasselt PM, Rötig A, Delahodde A, Prokisch H, Fuchs SA, Paquis-Flucklinger V Abstract MDH2 encodes mitochondrial malate dehydrogenase (MDH), which is essential for the conversion of malate to oxaloacetate as part of the proper functioning of the Krebs cycle. We report bi-allelic pathogenic mutations in MDH2 in three unrelated subjects presenting with early-onset generalized hypotonia, psychomotor delay, refractory epilepsy, and elevated lactate in the blood and cerebrospinal fluid. Functional studies in fibroblasts from affected subjects showed both an apparently complete loss of MDH2 levels and MDH2 enzymatic activity close to null. Metabolomics analyses demonstrated a significant concomitant accumulation of the MDH substrate, malate, and fumarate, its immediate precursor in the Krebs cycle, in affected subjects' fibroblasts. Lentiviral complementation with wild-type MDH2 cDNA restored MDH2 levels and mitochondrial MDH activity. Additionally, introduction of the three missense mutations from the affected subjects into Saccharomyces cerevisiae provided functional evidence to support their pathogenicity. Disruption of the Krebs cycle is a hallmark of cancer, and MDH2 has been recently identified as a novel pheochromocytoma and paraganglioma susceptibility gene. We show that loss-of-function mutations in MDH2 are also associated with severe neurological clinical presentations in children. PMID: 27989324 [PubMed - as supplied by publisher]

Related Articles Genome-wide Association Study Identifies 27 Loci Influencing Concentrations of Circulating Cytokines and Growth Factors. Am J Hum Genet. 2016 Dec 13;: Authors: Ahola-Olli AV, Würtz P, Havulinna AS, Aalto K, Pitkänen N, Lehtimäki T, Kähönen M, Lyytikäinen LP, Raitoharju E, Seppälä I, Sarin AP, Ripatti S, Palotie A, Perola M, Viikari JS, Jalkanen S, Maksimow M, Salomaa V, Salmi M, Kettunen J, Raitakari OT Abstract Circulating cytokines and growth factors are regulators of inflammation and have been implicated in autoimmune and metabolic diseases. In this genome-wide association study (GWAS) of up to 8,293 Finns we identified 27 genome-widely significant loci (p < 1.2 × 10(-9)) for one or more cytokines. Fifteen of the associated variants had expression quantitative trait loci in whole blood. We provide genetic instruments to clarify the causal roles of cytokine signaling and upstream inflammation in immune-related and other chronic diseases. We further link inflammatory markers with variants previously associated with autoimmune diseases such as Crohn disease, multiple sclerosis, and ulcerative colitis and hereby elucidate the molecular mechanisms underpinning these diseases and suggest potential drug targets. PMID: 27989323 [PubMed - as supplied by publisher]

Related Articles Comparative metabolomics reveals the mechanism of avermectin production enhancement by S-adenosylmethionine. J Ind Microbiol Biotechnol. 2016 Dec 17; Authors: Tian P, Cao P, Hu D, Wang D, Zhang J, Wang L, Zhu Y, Gao Q Abstract It was found that S-adenosylmethionine (SAM) could effectively improve avermectin titer with 30-60 μg/mL addition to FH medium. To clearly elucidate the mechanism of SAM on intracellular metabolites of Streptomyces avermitilis, a GC-MS-based comparative metabolomics approach was carried out. First, 230 intracellular metabolites were identified and 14 of them remarkably influenced avermectin biosynthesis were discriminative biomarkers between non-SAM groups and SAM-treated groups by principal components analysis (PCA) and partial least squares (PLS). Based on further key metabolic pathway analyses, these biomarkers, such as glucose, oxaloacetic acid, fatty acids (in soybean oil), threonine, valine, and leucine, were identified as potentially beneficial precursors and added in medium. Compared with single-precursor feeding, the combined feeding of the precursors and SAM markedly increased the avermectin titer. The co-feeding approach not only directly verified our hypothesis on the mechanism of SAM by comparative metabolomics, but also provided a novel strategy to increase avermectin production. PMID: 27988821 [PubMed - as supplied by publisher]

Related Articles Energy metabolism and metabolomics response of Pacific white shrimp Litopenaeus vannamei to sulfide toxicity. Aquat Toxicol. 2016 Dec 12;183:28-37 Authors: Li T, Li E, Suo Y, Xu Z, Jia Y, Qin JG, Chen L, Gu Z Abstract The toxicity and poisoning mechanisms of sulfide were studied in Litopenaeus vannamei from the perspective of energy metabolism and metabolomics. The lethal concentrations of sulfide in L. vannamei (LC50) at 24h, 48h, 72h, and 96h were determined. Sulfide at a concentration of 0, 1/10 (425.5μg/L), and 1/5 (851μg/L) of the LC50 at 96h was used to test the metabolic responses of L. vannamei for 21days. The chronic exposure of shrimp to a higher sulfide concentration of 851μg/L decreased shrimp survival but did not affect weight gain or the hepatopancreas index. The glycogen content in the hepatopancreas and muscle and the activity of hepatopancreas cytochrome C oxidase of the shrimp exposed to all sulfide concentrations were significantly lower, and the serum glucose and lactic acid levels and lactic acid dehydrogenase activity were significantly lower than those in the control. Metabolomics assays showed that shrimp exposed to sulfide had lower amounts of serum pyruvic acid, succinic acid, glycine, alanine, and proline in the 425.5μg/L group and phosphate, succinic acid, beta-alanine, serine, and l-histidine in the 851μg/L group than in the control. Chronic sulfide exposure could disturb protein synthesis in shrimp but enhance gluconeogenesis and substrate absorption for ATP synthesis and tricarboxylic acid cycles to provide extra energy to cope with sulfide stress. Chronic sulfide exposure could adversely affect the health status of L. vannamei, as indicated by the high amounts of serum n-ethylmaleamic acid, pyroglutamic acid, aspartic acid and phenylalanine relative to the control. This study indicates that chronic exposure of shrimp to sulfide can decrease health and lower survival through functional changes in gluconeogenesis, protein synthesis and energy metabolism. PMID: 27988416 [PubMed - as supplied by publisher]

Related Articles Unsaturated plasma phospholipids are consistently lower in the patients diagnosed with gestational diabetes mellitus throughout pregnancy: A longitudinal metabolomics study of Chinese pregnant women part 1. Clin Chim Acta. 2016 Dec 14;: Authors: Law KP, Mao X, Han TL, Zhang H Abstract BACKGROUND: Gestational diabetes mellitus (GDM) is a milder degree of hyperglycaemia diagnosed during pregnancy that can lead to serious, long-term consequences for both mother and foetus. The pathophysiology of GDM is not fully understood. The number of pregnant women diagnosed with GDM has been steadily increasing, but effective screening tools for early risk stratification are still missing. The emerging field of metabolomics has the potential to provide new insights and as a result is increasingly being used in studies of GDM. However, no study to date has investigated the longitudinal changes associated with GDM as pregnancy progresses. We investigated maternal plasma of a longitudinal cohort of normal pregnancies and pregnancies complicated by GDM. METHODS: Based on ultra-performance hydrophilic interaction liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry, an untargeted metabolomics study was performed to explore the changes in the plasma metabolome of GDM cases and healthy controls. Innovative sample preparation and multilevel statistical methods were employed to enhance our ability to analyse the longitudinal plasma samples by LC-MS. RESULTS: A number of polyunsaturated or chemically modified phospholipids were significantly lower in the plasma of pregnant women that developed GDM when compared to healthy controls, while no difference was observed for the saturated phospholipids. The reduction of these lipid species in the participants that developed GDM could be detected as early in the first trimester and the changes were independent of the stage of gestation and the steroid hormones in the plasma. CONCLUSIONS: These differences observed in our study were detected well before the onset of GDM, and might provide further insights into the etiology or pathophysiology of GDM. PMID: 27988319 [PubMed - as supplied by publisher]

Related Articles Urinary metabolomics revealed arsenic exposure related to metabolic alterations in general Chinese pregnant women. J Chromatogr A. 2016 Dec 10;: Authors: Li H, Wang M, Liang Q, Jin S, Sun X, Jiang Y, Pan X, Zhou Y, Peng Y, Zhang B, Zhou A, Zhang Y, Chen Z, Cao J, Zhang H, Xia W, Zheng T, Cai Z, Li Y, Xu S Abstract Arsenic exposure is considered a major environmental threat to human health. It is already known that high-level arsenic exposure has adverse effects on human health. Since the pregnant women are known to be more susceptible to some chemical exposures than ordinary people, the understanding regarding the health effects of low-level arsenic exposure on pregnant women is critical and remains unclear. The aim of this study is to investigate the urinary metabolic changes of pregnant women exposed to low-dose arsenic, and to identify biomarkers from metabolomics analysis. Urine samples of 246 pregnant women were collected in the first trimester of pregnancy and were divided into three groups based on the tertile distribution of urinary arsenic concentrations which were determined using inductively coupled plasma mass spectrometry (ICP-MS). Changes in the metabolite profile were measured using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS). Arsenic- related metabolic biomarkers were investigated by comparing the samples of the first and third tertiles of arsenic exposure classifications using a partial least-squares discriminant model (PLS-DA). Nine urine potential biomarkers were putatively identified, including LysoPC (14:0), glutathione, 18-carboxy-dinor-LTE4, 20-COOH-LTE4, cystathionine ketimin, 1-(beta-d-ribofuranosyl)-1,4-dihydronicotinamide, thiocysteine, p-cresol glucuronide and vanillactic acid. The obtained results showed that environmental arsenic exposure, even at low levels, could cause metabolite alterations in pregnant women which might be associated with adverse health outcomes. This is the first report on metabolic changes in pregnant women for arsenic exposure. The findings may be valuable for the arsenic risk assessment for pregnant women. PMID: 27988079 [PubMed - as supplied by publisher]

Dietary taurine supplementation ameliorates the lethal effect of phenanthrene but not the bioaccumulation in a marine teleost, red sea bream, Pagrus major. Ecotoxicol Environ Saf. 2016 Dec 14;137:272-280 Authors: Hano T, Ito M, Ito K, Kono K, Ohkubo N Abstract The present study was performed to evaluate the effect of dietary taurine on the hepatic metabolic profiles of red sea bream (Pagrus major) and on phenanthrene (a polyaromatic hydrocarbon) toxicity and bioaccumulation. The fish were fed a diet supplemented with 0% (TAU0%), 0.5% (TAU0.5%), or 5% (TAU5%) taurine for 40-55d and subjected to phenanthrene acute toxicity and bioaccumulation tests. Taurine deficiency in feed severely affected the hepatic metabolic profiles of fish, which indicated a complementary physiological response to taurine deficiency. For the acute toxicity test, fish were fed the test diets for 55d and were then exposed to 0-893µg/L phenanthrene for 96h. Tolerance to phenanthrene was significantly improved by 0.5% of taurine inclusion in feed relative to TAU0%, but not by 5.0% inclusion. Reduced glutathione in the liver, which acts as an oxygen-free radical scavenger, was associated with a reduction in the toxicity of phenanthrene. For the bioaccumulation test, fish were fed the test diets for 40d and were thereafter chronically exposed to 20µg/L phenanthrene for 13d followed by depuration for 3d. The activity of hepatic biomarker, ethoxyresorufin-O-deethylase, was increased by phenanthrene exposure in the taurine inclusion groups. However, phenanthrene concentrations in the liver and muscle of fish fed TAU5.0% tended to be higher than those of fish fed TAU0% and TAU0.5% during the exposure period. These results indicate that 0.5% of taurine inclusion in feed plays an important role in the alleviation of phenanthrene toxicity but not bioaccumulation. Furthermore, larger amount of taurine inclusion (TAU5%) did not show marked beneficial effects against phenanthrene exposure. This study provides insight about a major concern of environmental contaminants into aquatic environment and can be effectively used for improvement of aquaculture. PMID: 27987481 [PubMed - as supplied by publisher]

Urinary metabolic profiling of cisplatin nephrotoxicity and nephroprotective effects of Orthosiphon stamineus leaves elucidated by (1)H NMR spectroscopy. J Pharm Biomed Anal. 2016 Dec 08;135:20-30 Authors: Pariyani R, Ismail IS, Azam A, Khatib A, Abas F, Shaari K, Hamza H Abstract Orthosiphon stamineus (OS) is a popular medicinal herb used in traditional Chinese medicine as a diuretic agent and for renal system disorders. This study employed (1)H NMR based metabolomics approach to investigate the possible protective activity of OS in cisplatin induced nephrotoxicity owing to its diuretic and antioxidant activities. Aqueous (OSAE) and 50% aqueous ethanolic (OSFE) extracts of OS leaves were orally administered at 400mg/kg BW doses to rats which were then intraperitoneally injected with cisplatin at 5mg/kg BW dose. The (1)H NMR profile of the urine samples collected on day 5 after cisplatin administration were analyzed by multivariate pattern recognition techniques, whereby 19 marker metabolites suggestive in the involvement of TCA cycle, disturbed energy metabolism, altered gut microflora and BCAA metabolism pathways were identified. It was observed that OSFE caused significant changes (p<0.05) in the levels of 8 markers namely leucine, acetate, hippurate, lysine, valine, 2-oxoglutarate, 3-HBT and acetoacetate resulting in a moderate ameliorative effect, however, it did not completely protect from nephrotoxicity. OSAE did not demonstrate significant down regulatory effects on any markers, albeit, it potentiated the cisplatin nephrotoxicity by inducing significant increase in glucose, glycine, creatinine, citrate, TMAO, acetate and creatine levels. A Principal Component Analysis (PCA) of the (1)H NMR spectra of OS extracts identified that OSFE had higher concentrations of the secondary metabolites such as caffeic acid, chlorogenic acid, protocatechuic acid and orthosiphol, among others. Whereas, OSAE was characterized by higher concentrations of acetate, lactate, succinic acid, valine and phosphatidylcholine. This research denotes the first comprehensive analysis to identify the effects of OS extracts on cisplatin nephrotoxicity. PMID: 27987392 [PubMed - as supplied by publisher]

Related Articles The Evolution of Soybean Knowledge Base (SoyKB). Methods Mol Biol. 2017;1533:149-159 Authors: Joshi T, Wang J, Zhang H, Chen S, Zeng S, Xu B, Xu D Abstract Soybean Knowledge Base (SoyKB) is a comprehensive all-inclusive web resource for bridging the gap between soybean translational genomics and molecular breeding. It provides information for six entities including genes/proteins, microRNAs (miRNAs)/small interfering RNAs (sRNA), metabolites, single nucleotide polymorphisms (SNPs), and plant introduction lines and traits. It has a user-friendly web interface publicly available at http://soykb.org , which integrates and presents data in an intuitive manner to the soybean researchers, breeders, and consumers. It incorporates several informatics and analytical tools for integrating and merging various multi-omics datasets. PMID: 27987168 [PubMed - in process]

Related Articles The FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2. Cell Rep. 2016 Dec 09;: Authors: Swuec P, Renault L, Borg A, Shah F, Murphy VJ, van Twest S, Snijders B, Deans AJ, Costa A Abstract Activation of the main DNA interstrand crosslink repair pathway in higher eukaryotes requires mono-ubiquitination of FANCI and FANCD2 by FANCL, the E3 ligase subunit of the Fanconi anemia core complex. FANCI and FANCD2 form a stable complex; however, the molecular basis of their ubiquitination is ill defined. FANCD2 mono-ubiquitination by FANCL is stimulated by the presence of the FANCB and FAAP100 core complex components, through an unknown mechanism. How FANCI mono-ubiquitination is achieved remains unclear. Here, we use structural electron microscopy, combined with crosslink-coupled mass spectrometry, to find that FANCB, FANCL, and FAAP100 form a dimer of trimers, containing two FANCL molecules that are ideally poised to target both FANCI and FANCD2 for mono-ubiquitination. The FANCC-FANCE-FANCF subunits bridge between FANCB-FANCL-FAAP100 and the FANCI-FANCD2 substrate. A transient interaction with FANCC-FANCE-FANCF alters the FANCI-FANCD2 configuration, stabilizing the dimerization interface. Our data provide a model to explain how equivalent mono-ubiquitination of FANCI and FANCD2 occurs. PMID: 27986592 [PubMed - as supplied by publisher]

Related Articles Butia spp. (Arecaceae) LC-MS-based metabolomics for species and geographical origin discrimination. J Agric Food Chem. 2016 Dec 16; Authors: Hoffmann JF, Carvalho IR, Barbieri RL, Rombaldi CV, Chaves FC Abstract The metabolic variability of fruit from Butia spp. (Arecaceae) genotypes from different geographical locations was characterized using untargeted metabolomics by liquid chromatography-mass spectrometry (LC-MS) followed by multivariate data analyses. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) from LC-MS data sets showed a clear distinction among B. catarinensis, B. odorata, B. paraguayensis, and B. yatay. The major metabolites that contributed to species discrimination were primary metabolites including sugars and organic acids, and specialized metabolites such as tetrahydroxy-trans-stilbene and rutin. B. odorata fruit from Tapes, RS showed a high content of organic acids and flavonoids, while B. odorata fruits from Capão do Leão, RS showed a high sugar content. The results demonstrate that LC-ESI-qToF-MS-based metabolic profiling coupled with chemometric analysis can be used to discriminate among Butia species and between geographical origins of Butia odorata, and to identify primary and specialized metabolites responsible for the discrimination. PMID: 27984853 [PubMed - as supplied by publisher]