PubMed

TREM2 Maintains Microglial Metabolic Fitness in Alzheimer's Disease. Cell. 2017 Aug 10;170(4):649-663.e13 Authors: Ulland TK, Song WM, Huang SC, Ulrich JD, Sergushichev A, Beatty WL, Loboda AA, Zhou Y, Cairns NJ, Kambal A, Loginicheva E, Gilfillan S, Cella M, Virgin HW, Unanue ER, Wang Y, Artyomov MN, Holtzman DM, Colonna M Abstract Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress. Combined metabolomics and RNA sequencing (RNA-seq) linked this anomalous autophagy to defective mammalian target of rapamycin (mTOR) signaling, which affects ATP levels and biosynthetic pathways. Metabolic derailment and autophagy were offset in vitro through Dectin-1, a receptor that elicits TREM2-like intracellular signals, and cyclocreatine, a creatine analog that can supply ATP. Dietary cyclocreatine tempered autophagy, restored microglial clustering around plaques, and decreased plaque-adjacent neuronal dystrophy in TREM2-deficient mice with amyloid-β pathology. Thus, TREM2 enables microglial responses during AD by sustaining cellular energetic and biosynthetic metabolism. PMID: 28802038 [PubMed - in process]

Related Articles Identification and Partial Structural Characterization of Mass Isolated Valsartan and Its Metabolite with Messenger Tagging Vibrational Spectroscopy. J Am Soc Mass Spectrom. 2017 Aug 11;: Authors: Gorlova O, Colvin SM, Brathwaite A, Menges FS, Craig SM, Miller SJ, Johnson MA Abstract Recent advances in the coupling of vibrational spectroscopy with mass spectrometry create new opportunities for the structural characterization of metabolites with great sensitivity. Previous studies have demonstrated this scheme on 300 K ions using very high power free electron lasers in the fingerprint region of the infrared. Here we extend the scope of this approach to a single investigator scale as well as extend the spectral range to include the OH stretching fundamentals. This is accomplished by detecting the IR absorptions in a linear action regime by photodissociation of weakly bound N2 molecules, which are attached to the target ions in a cryogenically cooled, rf ion trap. We consider the specific case of the widely used drug Valsartan and two isomeric forms of its metabolite. Advantages and challenges of the cold ion approach are discussed, including disentangling the role of conformers and the strategic choices involved in the selection of the charging mechanism that optimize spectral differentiation among candidate structural isomers. In this case, the Na(+) complexes are observed to yield sharp resonances in the high frequency NH and OH stretching regions, which can be used to easily differentiate between two isomers of the metabolite. Graphical Abstract ᅟ. PMID: 28801884 [PubMed - as supplied by publisher]

Related Articles Vitamin B6 is essential for serine de novo biosynthesis. J Inherit Metab Dis. 2017 Aug 11;: Authors: Ramos RJ, Pras-Raves ML, Gerrits J, van der Ham M, Willemsen M, Prinsen H, Burgering B, Jans JJ, Verhoeven-Duif NM Abstract Pyridoxal 5'-phosphate (PLP), the metabolically active form of vitamin B6, plays an essential role in brain metabolism as a cofactor in numerous enzyme reactions. PLP deficiency in brain, either genetic or acquired, results in severe drug-resistant seizures that respond to vitamin B6 supplementation. The pathogenesis of vitamin B6 deficiency is largely unknown. To shed more light on the metabolic consequences of vitamin B6 deficiency in brain, we performed untargeted metabolomics in vitamin B6-deprived Neuro-2a cells. Significant alterations were observed in a range of metabolites. The most surprising observation was a decrease of serine and glycine, two amino acids that are known to be elevated in the plasma of vitamin B6 deficient patients. To investigate the cause of the low concentrations of serine and glycine, a metabolic flux analysis on serine biosynthesis was performed. The metabolic flux results showed that the de novo synthesis of serine was significantly reduced in vitamin B6-deprived cells. In addition, formation of glycine and 5-methyltetrahydrofolate was decreased. Thus, vitamin B6 is essential for serine de novo biosynthesis in neuronal cells, and serine de novo synthesis is critical to maintain intracellular serine and glycine. These findings suggest that serine and glycine concentrations in brain may be deficient in patients with vitamin B6 responsive epilepsy. The low intracellular 5-mTHF concentrations observed in vitro may explain the favourable but so far unexplained response of some patients with pyridoxine-dependent epilepsy to folinic acid supplementation. PMID: 28801717 [PubMed - as supplied by publisher]

Related Articles Calcium signaling and cell cycle: Progression or death. Cell Calcium. 2017 Jul 25;: Authors: Humeau J, Bravo-San Pedro JM, Vitale I, Nuñez L, Villalobos C, Kroemer G, Senovilla L Abstract Cytosolic Ca(2+) concentration levels fluctuate in an ordered manner along the cell cycle, in line with the fact that Ca(2+) is involved in the regulation of cell proliferation. Cell proliferation should be an error-free process, yet is endangered by mistakes. In fact, a complex network of proteins ensures that cell cycle does not progress until the previous phase has been successfully completed. Occasionally, errors occur during the cell cycle leading to cell cycle arrest. If the error is severe, and the cell cycle checkpoints work perfectly, this results into cellular demise by activation of apoptotic or non-apoptotic cell death programs. Cancer is characterized by deregulated proliferation and resistance against cell death. Ca(2+) is a central key to these phenomena as it modulates signaling pathways that control oncogenesis and cancer progression. Here, we discuss how Ca(2+) participates in the exogenous and endogenous signals controlling cell proliferation, as well as in the mechanisms by which cells die if irreparable cell cycle damage occurs. Moreover, we summarize how Ca(2+) homeostasis remodeling observed in cancer cells contributes to deregulated cell proliferation and resistance to cell death. Finally, we discuss the possibility to target specific components of Ca(2+) signal pathways to obtain cytostatic or cytotoxic effects. PMID: 28801101 [PubMed - as supplied by publisher]

Related Articles Immediate reduction of serum citrulline but no change of steroid profile after initiation of metformin in individuals with type 2 diabetes. J Steroid Biochem Mol Biol. 2017 Aug 08;: Authors: Breier M, Wahl S, Prehn C, Ferrari U, Sacco V, Weise M, Grallert H, Adamski J, Lechner A Abstract Metformin is the most important first-line treatment for type 2 diabetes mellitus (T2DM) but its exact mode of action remains unknown. In this study, we used targeted metabolomics to gain new insights into the metabolic effects of metformin in humans with T2DM. We also examined changes in the serum steroid hormone profile. We quantified 167 serum metabolites and 19 steroid hormones using liquid chromatography-tandem mass spectrometry at three time points in individuals with previously untreated T2DM: before the start of metformin therapy (time point A), after the first dose (B) and after short-term therapy for 4-6 weeks (C). For metabolite analysis, we split the study cohort into a discovery and a replication study of 88 and 45 subjects, respectively. The statistical analysis was done using linear mixed-effects models. Among the metabolites quantified, citrulline showed the most pronounced changes. Compared to its baseline serum concentration, citrulline was reduced by 17% after the first dose of metformin (p=1.34E-07) and by 24% after short-term therapy (p=2.84E-08) in the discovery study. These results were confirmed in the replication study. The only other metabolite significantly changed after correction for multiple testing was PC ae C36:4 between baseline and 4-6 weeks. The serum steroid hormone profile showed no significant changes after metformin intake. In summary, we observed an immediate and sustained reduction of serum citrulline by metformin in humans. This may be relevant for some of the wanted or unwanted effects of the drug. PMID: 28801099 [PubMed - as supplied by publisher]

Related Articles Solid-phase analytical derivatization for gas-chromatography-mass-spectrometry-based metabolomics. J Biosci Bioeng. 2017 Aug 08;: Authors: Takeo E, Sasano R, Shimma S, Bamba T, Fukusaki E Abstract A novel derivatization method for gas chromatography/mass spectrometry (GC/MS)-based metabolomics was developed, based on solid-phase analytical derivatization (SPAD) with methoximation followed by trimethylsilylation. This SPAD method realized derivatization on solid phases combining strong anion exchange with strong cation exchange. To omit a sample condensation process, GC/MS injection was performed using a large-volume injection mode. This mode uses a stomach-shaped insert, and enables a large quantity of sample to be vaporized and introduced into the GC/MS system. In the present study, several parameters were investigated for each SPAD step. The optimal derivatization conditions were determined to be 3-min-methoximation with 5 μL of >5% methoxyamine solution, and 10-min-trimethylsilylation with 25 μL of N-methyl-N-trimethylsilyl-trifluoroacetamide (MSTFA). Derivatized analytes were effectively eluted with 25 μL of n-hexane. The influences of coexisting substances were also investigated. Coexisting saccharides did not significantly affect the derivatization of analytes. Moreover, saccharides were efficiently washed out using 80% (v/v) acetonitrile in water. The influences of coexisting sodium chloride were negated by dilution of the sample solution with water. The developed method enables the derivatization of both anionic and cationic metabolites, and high-throughput sample preparation. The coverage of detectable metabolites for the developed method was similar to that of the conventional method. This is the first report of a SPAD-based human plasma metabolome analysis protocol. PMID: 28800906 [PubMed - as supplied by publisher]

Biomarker Research in Parkinson's Disease Using Metabolite Profiling. Metabolites. 2017 Aug 11;7(3): Authors: Havelund JF, Heegaard NHH, Færgeman NJK, Gramsbergen JB Abstract Biomarker research in Parkinson's disease (PD) has long been dominated by measuring dopamine metabolites or alpha-synuclein in cerebrospinal fluid. However, these markers do not allow early detection, precise prognosis or monitoring of disease progression. Moreover, PD is now considered a multifactorial disease, which requires a more precise diagnosis and personalized medication to obtain optimal outcome. In recent years, advanced metabolite profiling of body fluids like serum/plasma, CSF or urine, known as "metabolomics", has become a powerful and promising tool to identify novel biomarkers or "metabolic fingerprints" characteristic for PD at various stages of disease. In this review, we discuss metabolite profiling in clinical and experimental PD. We briefly review the use of different analytical platforms and methodologies and discuss the obtained results, the involved metabolic pathways, the potential as a biomarker and the significance of understanding the pathophysiology of PD. Many of the studies report alterations in alanine, branched-chain amino acids and fatty acid metabolism, all pointing to mitochondrial dysfunction in PD. Aromatic amino acids (phenylalanine, tyrosine, tryptophan) and purine metabolism (uric acid) are also altered in most metabolite profiling studies in PD. PMID: 28800113 [PubMed]

A Comprehensive Metabolomics Study to Assess Longitudinal Biochemical Changes and Potential Early Biomarkers in NOD Mice that Progress to Diabetes. J Proteome Res. 2017 Aug 11;: Authors: Buchwald P, Tamayo-Garcia A, Ramamoorthy S, Garcia-Contreras M, Mendez AJ, Ricordi C Abstract A global non-targeted longitudinal metabolomics study was carried out in male and female NOD mice to characterize the time-profile of the changes in the metabolic signature caused by onset of type 1 diabetes (T1D) and identify possible early biomarkers in T1D progressors. Metabolomics profiling of samples collected at five different time-points identified 676 and 706 biochemicals in blood and feces, respectively. Several metabolites were expressed at significantly different levels in progressors at all time-points, and their proportion increased strongly following onset of hyperglycemia. At the last time-point, when all progressors were diabetic, a large percentage of metabolites had significantly different levels: 57.8% in blood and 27.8% in feces. Metabolic pathways most strongly affected included the carbohydrate, lipid, branched-chain amino acid, and oxidative ones. Several biochemicals showed considerable (>4×) change. Maltose, 3-hydroxybutyric acid, and kojibiose increased, while 1,5-anhydroglucitol decreased more than 10-fold. At the earliest time-point (6-week), differences between the metabolic signatures of progressors and non-progressors were relatively modest. Nevertheless, several compounds had significantly different levels and show promise as possible early T1D biomarkers. They include fatty acid phosphocholine derivatives from the phosphatidylcholine sub-pathway (elevated in both blood and feces) as well as serotonin, ribose, and arabinose (increased) in blood plus 13-HODE, tocopherol (increased), diaminopimelate, valerate, hydroxymethylpyrimidine, and dulcitol (decreased) in feces. A combined metabolic signature based on these compounds might serve as an early predictor of T1D-progressors. PMID: 28799767 [PubMed - as supplied by publisher]

Related Articles Analysis of Urine Composition in Type II Diabetic Mice after Intervention Therapy Using Holothurian Polypeptides. Front Chem. 2017;5:54 Authors: Li Y, Xu J, Su X Abstract Hydrolysates and peptide fractions (PF) obtained from sea cucumber with commercial enzyme were studied on the hyperglycemic and renal protective effects on db/db rats using urine metabolomics. Compared with the control group the polypeptides from the two species could significantly reduce the urine glucose and urea. We also tried to address the compositions of highly expressed urinary proteins using a proteomics approach. They were serum albumins, AMBP proteins, negative trypsin, elastase, and urinary protein, GAPDH, a receptor of urokinase-type plasminogen activator (uPAR), and Ig kappa chain C region. We used the electronic nose to quickly detect changes in the volatile substances in mice urine after holothurian polypeptides (HPP) fed, and the results show it can identify the difference between treatment groups with the control group without overlapping. The protein express mechanism of HPP treating diabetes was discussed, and we suggested these two peptides with the hypoglycemic and renal protective activity might be utilized as nutraceuticals. PMID: 28798909 [PubMed]

Related Articles High Resolution UHPLC-MS Metabolomics and Sedative-Anxiolytic Effects of Latua pubiflora: A Mystic Plant used by Mapuche Amerindians. Front Pharmacol. 2017;8:494 Authors: Sánchez-Montoya EL, Reyes MA, Pardo J, Nuñez-Alarcón J, Ortiz JG, Jorge JC, Bórquez J, Mocan A, Simirgiotis MJ Abstract Latua pubiflora (Griseb) Phil. Is a native shrub of the Solanaceae family that grows freely in southern Chile and is employed among Mapuche aboriginals to induce sedative effects and hallucinations in religious or medicine rituals since prehispanic times. In this work, the pentobarbital-induced sleeping test and the elevated plus maze test were employed to test the behavioral effects of extracts of this plant in mice. The psychopharmacological evaluation of L. pubiflora extracts in mice determined that both alkaloid-enriched as well as the non-alkaloid extracts produced an increase of sleeping time and alteration of motor activity in mice at 150 mg/Kg. The alkaloid extract exhibited anxiolytic effects in the elevated plus maze test, which was counteracted by flumazenil. In addition, the alkaloid extract from L. pubiflora decreased [(3)H]-flunitrazepam binding on rat cortical membranes. In this study we have identified 18 tropane alkaloids (peaks 1-4, 8-13, 15-18, 21, 23, 24, and 28), 8 phenolic acids and related compounds (peaks 5-7, 14, 19, 20, 22, and 29) and 7 flavonoids (peaks 25-27 and 30-33) in extracts of L. pubiflora by UHPLC-PDA-MS which are responsible for the biological activity. This study assessed for the first time the sedative-anxiolytic effects of L. pubiflora in rats besides the high resolution metabolomics analysis including the finding of pharmacologically important tropane alkaloids and glycosylated flavonoids. PMID: 28798689 [PubMed]

Related Articles A metabolomic, geographic, and seasonal analysis of the contribution of pollen-derived adenosine to allergic sensitization. Metabolomics. 2016 Dec;12(12): Authors: Mueller GA, Thompson PM, DeRose EF, O'Connell TM, London RE Abstract BACKGROUND: Studies on ragweed and birch pollen extracts suggested that the adenosine content is an important factor in allergic sensitization. However, exposure levels from other pollens and considerations of geographic and seasonal factors have not been evaluated. OBJECTIVE: This study compared the metabolite profile of pollen species important for allergic disease, specifically measured the adenosine content, and evaluated exposure to pollen-derived adenosine. METHODS: An NMR metabolomics approach was used to measure metabolite concentrations in twenty-six pollen extracts. Pollen count data was analyzed from five cities to model exposure. RESULTS: A principal component analysis of the various metabolites identified by NMR showed that pollen extracts could be differentiated primarily by sugar content: glucose, fructose, sucrose, and myo-inositol. In extracts of 10 mg of pollen/ml, the adenosine was highest for grasses (45 μM) followed by trees (23 μM) and weeds (19 μM). Pollen count data showed that tree pollen was typically 5-10 times the amount of other pollens. At the daily peaks of tree, grass, and weed season the pollen-derived adenosine exposure per day is likely to only be 1.1, 0.11, and 0.12 μg, respectively. Seasonal models of pollen exposure and respiration suggest that it would be a rare event limited to tree pollen season for concentrations of pollen-derived adenosine to approach physiological levels. CONCLUSIONS: Sugar content and other metabolites may be useful in classifying pollens. Unless other factors create localized exposures that are very different from these models, pollen-derived adenosine is unlikely to be a major factor in allergic sensitization. PMID: 28798556 [PubMed]

Related Articles Working Up a Good Sweat - The Challenges of Standardising Sweat Collection for Metabolomics Analysis. Clin Biochem Rev. 2017 Feb;38(1):13-34 Authors: Hussain JN, Mantri N, Cohen MM Abstract INTRODUCTION: Human sweat is a complex biofluid of interest to diverse scientific fields. Metabolomics analysis of sweat promises to improve screening, diagnosis and self-monitoring of numerous conditions through new applications and greater personalisation of medical interventions. Before these applications can be fully developed, existing methods for the collection, handling, processing and storage of human sweat need to be revised. This review presents a cross-disciplinary overview of the origins, composition, physical characteristics and functional roles of human sweat, and explores the factors involved in standardising sweat collection for metabolomics analysis. METHODS: A literature review of human sweat analysis over the past 10 years (2006-2016) was performed to identify studies with metabolomics or similarly applicable 'omics' analysis. These studies were reviewed with attention to sweat induction and sampling techniques, timing of sweat collection, sweat storage conditions, laboratory derivation, processing and analytical platforms. RESULTS: Comparative analysis of 20 studies revealed numerous factors that can significantly impact the validity, reliability and reproducibility of sweat analysis including: anatomical site of sweat sampling, skin integrity and preparation; temperature and humidity at the sweat collection sites; timing and nature of sweat collection; metabolic quenching; transport and storage; qualitative and quantitative measurements of the skin microbiota at sweat collection sites; and individual variables such as diet, emotional state, metabolic conditions, pharmaceutical, recreational drug and supplement use. CONCLUSION: Further development of standard operating protocols for human sweat collection can open the way for sweat metabolomics to significantly add to our understanding of human physiology in health and disease. PMID: 28798503 [PubMed]

Related Articles Adipose tissue, metabolic and inflammatory responses to stroke are altered in obese mice. Dis Model Mech. 2017 Aug 10;: Authors: Haley MJ, Mullard G, Hollywood KA, Cooper GJ, Dunn WB, Lawrence CB Abstract Obesity is an independent risk factor for stroke, though several clinical studies have reported that obesity improves stroke outcome. Obesity is hypothesised to aid recovery by protecting against post-stroke catabolism. We therefore assessed whether obese mice had an altered metabolic and inflammatory response to stroke. Obese ob/ob mice underwent 20 min middle cerebral artery occlusion and 24 h reperfusion. Lipid metabolism and expression of inflammatory cytokines were assessed in the plasma, liver and adipose tissue. The obese-specific metabolic response to stroke was assessed in plasma using non-targeted UPLC-MS metabolomics coupled with univariate and multivariate analysis. Obesity had no effect on the extent of weight loss 24 h after stroke but affected the metabolic and inflammatory responses to stroke, predominantly affecting lipid metabolism. Specifically, obese mice had increases in plasma free fatty acids and expression of adipose lipolytic enzymes. Metabolomics identified several classes of metabolites affected by stroke in obese mice, including fatty acids and membrane lipids (glycerophospholipids, lysophospholipids and sphingolipids). Obesity also featured increases in inflammatory cytokines in the plasma and adipose tissue. Overall these results demonstrate that obesity affected the acute metabolic and inflammatory response to stroke and suggest a potential role for adipose tissue in this effect. These findings could have implications for longer-term recovery and also further highlight the importance of considering comorbidities in preclinical stroke research, especially when identifying biomarkers for stroke. However, further work is required to assess whether these changes translate into long-term effects on recovery. PMID: 28798136 [PubMed - as supplied by publisher]

Related Articles Venlafaxine exerts antidepressant effects possibly by activating MAPK-ERK1/2 and P13K-AKT pathways in the hippocampus. Behav Brain Res. 2017 Aug 07;: Authors: Shen P, Hu Q, Dong M, Bai S, Liang Z, Chen Z, Li P, Hu Z, Zhong X, Zhu D, Wang H, Xie P Abstract Serotonin noradrenaline reuptake inhibitors are effective antidepressant drugs, which include venlafaxine and duloxetine. Venlafaxine is commonly used in a clinical context, but the molecular biological mechanisms behind its effects have not been fully determined. Here, we explored the potential biological effects of venlafaxine on mouse hippocampus. Mice were randomly divided into two groups and injected daily with 0.9% NaCl solution or venlafaxine. A GC-MS-based metabolomic approach was used to identify possible metabolic differences between these groups, and the key proteins involved in the relevant pathways were validated by western blotting. In our experiments, 27 hippocampal metabolites that distinguished the venlafaxine group from the control group were identified. These differential metabolites were subjected to Ingenuity Pathway Analysis, which revealed that they were strongly related to two metabolic pathways (MAPK-ERK1/2 and P13K-AKT signaling pathways). Six key proteins, BDNF, p-c-Raf, p-MAPK, p-MEK, p-AKT, and CREB, were verified by western blotting and the results were consistent with the differential metabolites identified by GC-MS. This study sheds light on the biological mechanisms underlying the effects of venlafaxine. PMID: 28797602 [PubMed - as supplied by publisher]

Related Articles Glycosylation of KEAP1 links nutrient sensing to redox stress signaling. EMBO J. 2017 Aug 01;36(15):2233-2250 Authors: Chen PH, Smith TJ, Wu J, Siesser PF, Bisnett BJ, Khan F, Hogue M, Soderblom E, Tang F, Marks JR, Major MB, Swarts BM, Boyce M, Chi JT Abstract O-GlcNAcylation is an essential, nutrient-sensitive post-translational modification, but its biochemical and phenotypic effects remain incompletely understood. To address this question, we investigated the global transcriptional response to perturbations in O-GlcNAcylation. Unexpectedly, many transcriptional effects of O-GlcNAc transferase (OGT) inhibition were due to the activation of NRF2, the master regulator of redox stress tolerance. Moreover, we found that a signature of low OGT activity strongly correlates with NRF2 activation in multiple tumor expression datasets. Guided by this information, we identified KEAP1 (also known as KLHL19), the primary negative regulator of NRF2, as a direct substrate of OGT We show that O-GlcNAcylation of KEAP1 at serine 104 is required for the efficient ubiquitination and degradation of NRF2. Interestingly, O-GlcNAc levels and NRF2 activation co-vary in response to glucose fluctuations, indicating that KEAP1 O-GlcNAcylation links nutrient sensing to downstream stress resistance. Our results reveal a novel regulatory connection between nutrient-sensitive glycosylation and NRF2 signaling and provide a blueprint for future approaches to discover functionally important O-GlcNAcylation events on other KLHL family proteins in various experimental and disease contexts. PMID: 28663241 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling of apples from different production systems before and after controlled atmosphere (CA) storage studied by (1)H high resolution-magic angle spinning (HR-MAS) NMR. Food Chem. 2017 Oct 15;233:391-400 Authors: Vermathen M, Marzorati M, Diserens G, Baumgartner D, Good C, Gasser F, Vermathen P Abstract Determination of metabolic alterations in apples induced by such processes as different crop protection strategies or storage, are of interest to assess correlations with fruit quality or fruit disorders. Preliminary results proposed the metabolic discrimination of apples from organic (BIO), integrated (IP) and low-input (LI) production. To determine contributions of temporal metabolic developments and to define the type of metabolic changes during storage, (1)H high resolution-magic angle spinning (HR-MAS) NMR spectroscopy of apple pulp was performed before and after two time points of controlled atmosphere storage. Statistical analysis revealed similar metabolic changes over time for IP-, LI- and BIO-samples, mainly decreasing lipid and sucrose, and increasing fructose, glucose and acetaldehyde levels, which are potential contributors to fruit aroma. Across the production systems, BIO apples had consistently higher levels of fructose and monomeric phenolic compounds but lower levels of condensed polyphenols than LI and IP apples, while the remaining metabolites assimilated. PMID: 28530590 [PubMed - indexed for MEDLINE]

Related Articles A systems biology approach reveals major metabolic changes in the thermoacidophilic archaeon Sulfolobus solfataricus in response to the carbon source L-fucose versus D-glucose. Mol Microbiol. 2016 Dec;102(5):882-908 Authors: Wolf J, Stark H, Fafenrot K, Albersmeier A, Pham TK, Müller KB, Meyer BH, Hoffmann L, Shen L, Albaum SP, Kouril T, Schmidt-Hohagen K, Neumann-Schaal M, Bräsen C, Kalinowski J, Wright PC, Albers SV, Schomburg D, Siebers B Abstract Archaea are characterised by a complex metabolism with many unique enzymes that differ from their bacterial and eukaryotic counterparts. The thermoacidophilic archaeon Sulfolobus solfataricus is known for its metabolic versatility and is able to utilize a great variety of different carbon sources. However, the underlying degradation pathways and their regulation are often unknown. In this work, the growth on different carbon sources was analysed, using an integrated systems biology approach. The comparison of growth on L-fucose and D-glucose allows first insights into the genome-wide changes in response to the two carbon sources and revealed a new pathway for L-fucose degradation in S. solfataricus. During growth on L-fucose major changes in the central carbon metabolic network, as well as an increased activity of the glyoxylate bypass and the 3-hydroxypropionate/4-hydroxybutyrate cycle were observed. Within the newly discovered pathway for L-fucose degradation the following key reactions were identified: (i) L-fucose oxidation to L-fuconate via a dehydrogenase, (ii) dehydration to 2-keto-3-deoxy-L-fuconate via dehydratase, (iii) 2-keto-3-deoxy-L-fuconate cleavage to pyruvate and L-lactaldehyde via aldolase and (iv) L-lactaldehyde conversion to L-lactate via aldehyde dehydrogenase. This pathway as well as L-fucose transport shows interesting overlaps to the D-arabinose pathway, representing another example for pathway promiscuity in Sulfolobus species. PMID: 27611014 [PubMed - indexed for MEDLINE]

Related Articles Inflammation Thread Runs across Medical Laboratory Specialities. Mediators Inflamm. 2016;2016:4121837 Authors: Nydegger U, Lung T, Risch L, Risch M, Medina Escobar P, Bodmer T Abstract We work on the assumption that four major specialities or sectors of medical laboratory assays, comprising clinical chemistry, haematology, immunology, and microbiology, embraced by genome sequencing techniques, are routinely in use. Medical laboratory markers for inflammation serve as model: they are allotted to most fields of medical lab assays including genomics. Incessant coding of assays aligns each of them in the long lists of big data. As exemplified with the complement gene family, containing C2, C3, C8A, C8B, CFH, CFI, and ITGB2, heritability patterns/risk factors associated with diseases with genetic glitch of complement components are unfolding. The C4 component serum levels depend on sufficient vitamin D whilst low vitamin D is inversely related to IgG1, IgA, and C3 linking vitamin sufficiency to innate immunity. Whole genome sequencing of microbial organisms may distinguish virulent from nonvirulent and antibiotic resistant from nonresistant varieties of the same species and thus can be listed in personal big data banks including microbiological pathology; the big data warehouse continues to grow. PMID: 27493451 [PubMed - indexed for MEDLINE]

Related Articles Seminal plasma metabolomics approach for the diagnosis of unexplained male infertility. PLoS One. 2017;12(8):e0181115 Authors: Qiao S, Wu W, Chen M, Tang Q, Xia Y, Jia W, Wang X Abstract We used a gas chromatography-mass spectrometry (GC-MS) based metabolomics approach to obtain the metabolic profiling of unexplained male infertility (UMI), and identified seminal plasma biomarkers associated with UMI by a two-stage population study. A robust OPLS-DA model based on these identified metabolites was able to distinguish 82% of the UMI patients from health controls with a specificity of 92%. In this model, 44 metabolites were found differentially expressed in UMI subjects compared with health controls. By pathway enrichment analysis, we identified several major changed metabolic pathways related to UMI. Our findings provide new perspective for the diagnosis of UMI. PMID: 28797078 [PubMed - in process]

Related Articles Systems and synthetic biology perspective of the versatile plant-pathogenic and polysaccharide-producing bacterium Xanthomonas campestris. Microbiology. 2017 Aug 10;: Authors: Schatschneider S, Schneider J, Blom J, Létisse F, Niehaus K, Goesmann A, Vorhölter FJ Abstract Bacteria of the genus Xanthomonas are a major group of plant pathogens. They are hazardous to important crops and closely related to human pathogens. Being collectively a major focus of molecular phytopathology, an increasing number of diverse and intricate mechanisms are emerging by which they communicate, interfere with host signalling and keep competition at bay. Interestingly, they are also biotechnologically relevant polysaccharide producers. Systems biotechnology techniques have revealed their central metabolism and a growing number of remarkable features. Traditional analyses of Xanthomonas metabolism missed the Embden-Meyerhof-Parnas pathway (glycolysis) as being a route by which energy and molecular building blocks are derived from glucose. As a consequence of the emerging full picture of their metabolism process, xanthomonads were discovered to have three alternative catabolic pathways and they use an unusual and reversible phosphofructokinase as a key enzyme. In this review, we summarize the synthetic and systems biology methods and the bioinformatics tools applied to reconstruct their metabolic network and reveal the dynamic fluxes within their complex carbohydrate metabolism. This is based on insights from omics disciplines; in particular, genomics, transcriptomics, proteomics and metabolomics. Analysis of high-throughput omics data facilitates the reconstruction of organism-specific large- and genome-scale metabolic networks. Reconstructed metabolic networks are fundamental to the formulation of metabolic models that facilitate the simulation of actual metabolic activities under specific environmental conditions. PMID: 28795660 [PubMed - as supplied by publisher]