PubMed

Related Articles NMR-based investigation of the Drosophila melanogaster metabolome under the influence of daily cycles of light and temperature. Mol Biosyst. 2015 Sep 30; Authors: Gogna N, Singh VJ, Sheeba V, Dorai K Abstract We utilized an NMR-based metabolomic approach to profile the metabolites in Drosophila melanogaster that cycle with a daily rhythm. (1)H 1D and 2D NMR experiments were performed on whole-body extracts sampled from flies that experienced strong time cues in the form of both light and temperature cycles. Multivariate and univariate statistical analysis was used to identify those metabolites whose concentrations oscillate diurnally. We compared metabolite levels at two time points twelve hours apart, one close to the end of the day and the other close to the end of the night, and identified metabolites that differed significantly in their relative concentrations. We were able to identify 14 such metabolites whose concentrations differed significantly between the two time points. The concentrations of metabolites such as sterols, fatty acids, amino acids such as leucine, valine, isoleucine, alanine and lysine as well as other metabolites such as creatine, glucose, AMP and NAD were higher close to the end of the night, whereas the levels of lactic acid, and a few amino acids such as histidine and tryptophan were higher close to the end of the day. We compared signal intensities across 12 equally spaced time points for these 14 metabolites, in order to profile the changes in their levels across the day, since the NMR metabolite peak intensity is directly proportional to its molar concentration. Through this report we establish NMR-based metabolomics combined with multivariate statistical analysis as a useful method for future studies on the interactions between circadian clocks and metabolic processes. PMID: 26422411 [PubMed - as supplied by publisher]

Related Articles The metabolomics of asthma control: a promising link between genetics and disease. Immun Inflamm Dis. 2015 Sep;3(3):224-38 Authors: McGeachie MJ, Dahlin A, Qiu W, Croteau-Chonka DC, Savage J, Wu AC, Wan ES, Sordillo JE, Al-Garawi A, Martinez FD, Strunk RC, Lemanske RF, Liu AH, Raby BA, Weiss S, Clish CB, Lasky-Su JA Abstract Short-acting β agonists (e.g., albuterol) are the most commonly used medications for asthma, a disease that affects over 300 million people in the world. Metabolomic profiling of asthmatics taking β agonists presents a new and promising resource for identifying the molecular determinants of asthma control. The objective is to identify novel genetic and biochemical predictors of asthma control using an integrative "omics" approach. We generated lipidomic data by liquid chromatography tandem mass spectrometry (LC-MS), - using plasma samples from 20 individuals with asthma. The outcome of interest was a binary indicator of asthma control defined by the use of albuterol inhalers in the preceding week. We integrated metabolomic data with genome-wide genotype, gene expression, and methylation data of this cohort to identify genomic and molecular indicators of asthma control. A Conditional Gaussian Bayesian Network (CGBN) was generated using the strongest predictors from each of these analyses. Integrative and metabolic pathway over-representation analyses (ORA) identified enrichment of known biological pathways within the strongest molecular determinants. Of the 64 metabolites measured, 32 had known identities. The CGBN model based on four SNPs (rs9522789, rs7147228, rs2701423, rs759582) and two metabolites-monoHETE_0863 and sphingosine-1-phosphate (S1P) could predict asthma control with an AUC of 95%. Integrative ORA identified 17 significantly enriched pathways related to cellular immune response, interferon signaling, and cytokine-related signaling, for which arachidonic acid, PGE2 and S1P, in addition to six genes (CHN1, PRKCE, GNA12, OASL, OAS1, and IFIT3) appeared to drive the pathway results. Of these predictors, S1P, GNA12, and PRKCE were enriched in the results from integrative and metabolic ORAs. Through an integrative analysis of metabolomic, genomic, and methylation data from a small cohort of asthmatics, we implicate altered metabolic pathways, related to sphingolipid metabolism, in asthma control. These results provide insight into the pathophysiology of asthma control. PMID: 26421150 [PubMed]

Related Articles Metabolomics in childhood diabetes. Pediatr Diabetes. 2015 Sep 30; Authors: Frohnert BI, Rewers MJ Abstract Recent increases in the incidence of both type 1 (T1D) and type 2 diabetes (T2D) in children and adolescents point to the importance of environmental factors in the development of these diseases. Metabolomic analysis explores the integrated response of the organism to environmental changes. Metabolic profiling can identify biomarkers that are predictive of disease incidence and development, potentially providing insight into disease pathogenesis. This review provides an overview of the role of metabolomic analysis in diabetes research and summarizes recent research relating to the development of T1D and T2D in children. PMID: 26420304 [PubMed - as supplied by publisher]

Related Articles Metabolome analysis reveals the effect of carbon catabolite control on the poly(γ-glutamic acid) biosynthesis of Bacillus licheniformis ATCC 9945. J Biosci Bioeng. 2015 Sep 23; Authors: Mitsunaga H, Meissner L, Palmen T, Bamba T, Büchs J, Fukusaki E Abstract Poly(γ-glutamic acid) (PGA) is a polymer composed of l- and/or d-glutamic acids that is produced by Bacillus sp. Because the polymer has various features as water soluble, edible, non-toxic and so on, it has attracted attention as a candidate for many applications such as foods, cosmetics and so on. However, although it is well known that the intracellular metabolism of Bacillus sp. is mainly regulated by catabolite control, the effect of the catabolite control on the PGA producing Bacillus sp. is largely unknown. This study is the first report of metabolome analysis on the PGA producing Bacillus sp. that reveals the effect of carbon catabolite control on the metabolism of PGA producing Bacillus licheniformis ATCC 9945. Results showed that the cells cultivated in glycerol-containing medium showed higher PGA production than the cells in glucose-containing medium. Furthermore, metabolome analysis revealed that the activators of CcpA and CodY, global regulatory proteins of the intracellular metabolism, accumulated in the cells cultivated in glycerol-containing and glucose-containing medium, respectively, with CodY apparently inhibiting PGA production. Moreover, the cells seemed to produce glutamate from citrate and ammonium using glutamine synthetase/glutamate synthase. Pulsed addition of di-ammonium hydrogen citrate, as suggested by the metabolome result, was able to achieve the highest value so far for PGA production in B. licheniformis. PMID: 26419706 [PubMed - as supplied by publisher]

Related Articles Metabolomic charactetization of yeast cells after dehydration stress. Int Microbiol. 2014 Sep;17(3):131-9 Authors: López-Martínez G, Borrull A, Poblet M, Roy NR, Cordero-Otero R Abstract In this study, we analyzed the metabolite features of the yeasts Saccharomyces cerevisiae, Naumovia castellii, and Saccharomyces mikatae. The three species are closely related genetically but differ in their tolerance of desiccation stress. Specifically, we determined whether certain metabolites correlated with cell viability after stress imposition. The metabolomics profiles of these strains were compared before cell desiccation and after cell rehydration. In S. mikatae, the presence of lysine or glutamine during rehydration led to a 20% increase in survival whereas during dehydration the levels of both amino acids in this yeast were drastically reduced. [Int Microbiol 2014; 17(3):131-139]. PMID: 26419452 [PubMed - in process]

Related Articles Metabolic changes in rat urine after acute paraquat poisoning and discriminated by support vector machine. Biomed Chromatogr. 2015 Sep 29; Authors: Wen C, Wang Z, Zhang M, Wang S, Geng P, Sun F, Chen M, Lin G, Hu L, Ma J, Wang X Abstract Paraquat is quick-acting and non-selective, killing green plant tissue on contact, it is also toxic to human beings and animals. In this study, we developed a urine metabonomic method by gas chromatography-mass spectrometry to evaluate the effect of acute paraquat poisoning on rats. Pattern recognition analysis, including both partial least squares-discriminate analysis and principal component analysis revealed that acute paraquat poisoning induced metabolic perturbations. Compared to the control group, the level of benzeneacetic acid and hexadecanoic acid of the acute paraquat poisoning group (intragastric administration 36 mg/kg) increased, while the level of butanedioic acid, pentanedioic acid, altronic acid decreased. Based on these urinary metabolomics data, support vector machine was applied to discriminate the metabolomic change of paraquat groups from control group which achieved 100% classification accuracy. In conclusion, metabonomic method combined with support vector machine can be used as a useful diagnostic tool in paraquat poisoned rats. This article is protected by copyright. All rights reserved. PMID: 26419410 [PubMed - as supplied by publisher]

Related Articles Spatial H2O2 signaling specificity: H2O2 from chloroplasts and peroxisomes modulates the plant transcriptome differentially. Mol Plant. 2014 Jul;7(7):1191-210 Authors: Sewelam N, Jaspert N, Van Der Kelen K, Tognetti VB, Schmitz J, Frerigmann H, Stahl E, Zeier J, Van Breusegem F, Maurino VG Abstract Hydrogen peroxide (H2O2) operates as a signaling molecule in eukaryotes, but the specificity of its signaling capacities remains largely unrevealed. Here, we analyzed whether a moderate production of H2O2 from two different plant cellular compartments has divergent effects on the plant transcriptome. Arabidopsis thaliana overexpressing glycolate oxidase in the chloroplast (Fahnenstich et al., 2008; Balazadeh et al., 2012) and plants deficient in peroxisomal catalase (Queval et al., 2007; Inzé et al., 2012) were grown under non-photorespiratory conditions and then transferred to photorespiratory conditions to foster the production of H2O2 in both organelles. We show that H2O2 originating in a specific organelle induces two types of responses: one that integrates signals independently from the subcellular site of H2O2 production and another that is dependent on the H2O2 production site. H2O2 produced in peroxisomes induces transcripts involved in protein repair responses, while H2O2 produced in chloroplasts induces early signaling responses, including transcription factors and biosynthetic genes involved in production of secondary signaling messengers. There is a significant bias towards the induction of genes involved in responses to wounding and pathogen attack by chloroplastic-produced H2O2, including indolic glucosinolates-, camalexin-, and stigmasterol-biosynthetic genes. These transcriptional responses were accompanied by the accumulation of 4-methoxy-indol-3-ylmethyl glucosinolate and stigmasterol. PMID: 24908268 [PubMed - indexed for MEDLINE]

Biomarkers in Transplantation- Proteomics and Metabolomics. Ther Drug Monit. 2015 Aug 28; Authors: U C, Klawitter J, Klawitter J Abstract Modern multi-analyte "omics" technologies allow for the identification of molecular signatures that confer significantly more information than measurement of a single parameter as typically used in current medical diagnostics. Proteomics and metabolomics bioanalytical assays capture a large set of proteins and metabolites in body fluids, cells or tissues and, complementing genomics, assess the phenome. Proteomics and metabolomics contribute to the development of novel predictive clinical biomarkers in transplantation in two ways: They can be used to generate a diagnostic fingerprint or they can be used to discover individual proteins and metabolites of diagnostic potential.Much fewer metabolomics than proteomics biomarker studies in transplant patients have been reported and, in contrast to proteomics discovery studies, new lead metabolite markers have yet to emerge.Most clinical proteomics studies have been discovery studies. Several of these studies have assessed diagnostic sensitivity and specificity. Nevertheless, none of these newly discovered protein biomarkers has yet been implemented in clinical decision making in transplantation. The currently most advanced markers discovered in proteomics studies in transplant patients are the chemokines CXCL-9 and CXCL-10, which have successfully been validated in larger multi-center trials in kidney transplant patients. These chemokines can be measured using standard immunoassay platforms, which should facilitate clinical implementation. Based on the published evidence, it is reasonable to expect that these chemokine markers can help guiding and individualizing immunosuppressive regimens, may be able to predict acute and chronic T cell and anti-body mediated rejection and may be useful tools for risk stratification of kidney transplant patients. PMID: 26418702 [PubMed - as supplied by publisher]

Transcription factor StWRKY1 regulates phenylpropanoid metabolites conferring late blight resistance in potato. J Exp Bot. 2015 Sep 28; Authors: Yogendra KN, Kumar A, Sarkar K, Li Y, Pushpa D, Mosa KA, Duggavathi R, Kushalappa AC Abstract Quantitative resistance is polygenically controlled and durable, but the underlying molecular and biochemical mechanisms are poorly understood. Secondary cell wall thickening is a critical process in quantitative resistance, regulated by transcriptional networks. This paper provides compelling evidence on the functionality of StWRKY1 transcription factor, in a compatible interaction of potato-Phytophthora infestans, to extend our knowledge on the regulation of the metabolic pathway genes leading to strengthening the secondary cell wall. A metabolomics approach was used to identify resistance-related metabolites belonging to the phenylpropanoid pathway and their biosynthetic genes regulated by StWRKY1. The StWRKY1 gene in resistant potato was silenced to decipher its role in the regulation of phenylpropanoid pathway genes to strengthen the secondary cell wall. Sequencing of the promoter region of StWRKY1 in susceptible genotypes revealed the absence of heat shock elements (HSEs). Simultaneous induction of both the heat shock protein (sHSP17.8) and StWRKY1 following pathogen invasion enables functioning of the latter to interact with the HSE present in the resistant StWRKY1 promoter region. EMSA and luciferase transient expression assays further revealed direct binding of StWRKY1 to promoters of hydroxycinnamic acid amide (HCAA) biosynthetic genes encoding 4-coumarate:CoA ligase and tyramine hydroxycinnamoyl transferase. Silencing of the StWRKY1 gene was associated with signs of reduced late blight resistance by significantly increasing the pathogen biomass and decreasing the abundance of HCAAs. This study provides convincing evidence on the role of StWRKY1 in the regulation of downstream genes to biosynthesize HCAAs, which are deposited to reinforce secondary cell walls. PMID: 26417019 [PubMed - as supplied by publisher]

Deletion of glycerol channel aquaporin-9 (Aqp9) impairs long-term blood glucose control in C57BL/6 leptin receptor-deficient (db/db) obese mice. Physiol Rep. 2015 Sep;3(9) Authors: Spegel P, Chawade A, Nielsen S, Kjellbom P, Rützler M Abstract Deletion of the glycerol channel aquaporin-9 (Aqp9) reduces postprandial blood glucose levels in leptin receptor-deficient (db/db) obese mice on a C57BL/6 × C57BLKS mixed genetic background. Furthermore, shRNA-mediated reduction of Aqp9 expression reduces liver triacylglycerol (TAG) accumulation in a diet-induced rat model of obesity. The aim of this study was to investigate metabolic effects of Aqp9 deletion in coisogenic db/db mice of the C57BL/6 background. Aqp9(wt) db/db and Aqp9(-/-) db/db mice did not differ in body weight and liver TAG contents. On the C57BL/6 genetic background, we observed elevated plasma glucose in Aqp9(-/-) db/db mice (+1.1 mmol/L, life-time average), while plasma insulin concentration was reduced at the time of death. Glucose levels changed similarly in pentobarbital anesthetized, glucagon challenged Aqp9(wt) db/db and Aqp9(-/-) db/db mice. Liver transcriptional profiling did not detect differential gene expression between genotypes. Metabolite profiling revealed a sex independent increase in plasma glycerol (+55%) and glucose (+24%), and reduction in threonate (all at q < 0.1) in Aqp9(-/-) db/db mice compared to controls. Metabolite profiling thus confirms a role of AQP9 in glycerol metabolism of obese C57BL/6 db/db mice. In this animal model of obesity Aqp9 gene deletion elevates plasma glucose and does not alleviate hepatosteatosis. PMID: 26416971 [PubMed]

Detection of metabolites discriminating subtypes of thyroid cancer: molecular profiling of FFPE samples using the GC/MS approach. Mol Cell Endocrinol. 2015 Sep 25; Authors: Wojakowska A, Chekan M, Marczak Ł, Polanski K, Lange D, Pietrowska M, Widlak P Abstract One of the critical issues in thyroid cancer diagnostic is differentiation between follicular adenoma, follicular carcinoma and the follicular variant of papillary carcinoma, which in some cases is not possible based on histopathological features only. In this paper we performed molecular profiling of thyroid tissue aiming to identify metabolites characteristic for different types of thyroid cancer. FFPE tissue specimens were analysed from 5 different types of thyroid malignancies (follicular, papillary/classical variant, papillary/follicular variant, medullary and anaplastic cancers), benign follicular adenoma and normal thyroid. Extracted metabolites were identified and semi-quantified using the GC/MS approach. There were 28 metabolites identified, whose abundances were significantly different among different types of thyroid tumours, including lipids, carboxylic acids, and saccharides. We concluded, that multi-component metabolome signature could be used for classification of different subtypes of follicular thyroid lesions. Moreover, potential applicability of the GC/MS-based analysis of FFPE tissue samples in diagnostics of thyroid cancer has been proved. PMID: 26415588 [PubMed - as supplied by publisher]

Related Articles Intervention effects of puerarin on blood stasis in rats revealed by a (1)H NMR-based metabonomic approach. Phytomedicine. 2015 Mar 15;22(3):333-43 Authors: Zou ZJ, Liu ZH, Gong MJ, Han B, Wang SM, Liang SW Abstract Puerarin possesses a wide spectrum of biological activities including ameliorating effects on blood stasis, but the definite mechanism of this effect is still not known. In this study, a (1)H NMR-based plasma and urinary metabonomic approach was applied to comprehensively and holistically investigate the therapeutic effects of puerarin on blood stasis and its underlying mechanisms. Puerarin was injected intraperitoneally once daily for consecutive 7 days. The blood stasis rat model was established by placing the rats in ice-cold water during the time interval between two injections of adrenaline. With pattern recognition analysis, a clear separation of blood stasis model group and healthy control group was achieved and puerarin pretreatment group was located much closer to the control group than the model group, which was consistent with results of hemorheology studies. 15 and 10 potential biomarkers associated with blood stasis in plasma and urine, respectively, which were mainly involved in energy metabolism, lipid and membrane metabolisms, amino acid metabolism and gut microbiota metabolism, were identified. Puerarin could prevent blood stasis through partially regulating the disturbed metabolic pathways. This work highlights that metabonomics is a valuable tool for studying the essence of blood stasis as well as evaluating the efficacy of the corresponding drug treatment. PMID: 25837270 [PubMed - indexed for MEDLINE]

Related Articles The survival mechanisms of thermophiles at high temperatures: an angle of omics. Physiology (Bethesda). 2015 Mar;30(2):97-106 Authors: Wang Q, Cen Z, Zhao J Abstract Thermophiles are referred to as microorganisms with optimal growth temperatures of >60 °C. Over the past few years, a number of studies have been conducted regarding thermophiles, especially using the omics strategies. This review provides a systematic view of the survival physiology of thermophiles from an "omics" perspective, which suggests that the adaptive ability of thermophiles is based on a cooperative mode with multi-dimensional regulations integrating genomics, transcriptomics, and proteomics. PMID: 25729055 [PubMed - indexed for MEDLINE]

Related Articles [Metabonomic analysis of the serum from rat model with abnormal balgam syndrome of Uyghur medicine]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2015 Jan;40(1):18-24 Authors: Mosha G, Nurmaimaiti A, Zhang J, Abudula M, Huang J, Yunusi K Abstract OBJECTIVE: To investigate correlation between the change in metabolic components of serum and the abnormal balgam syndrome by using a rat model of abnormal balgam syndrome. METHODS: Male Wistar rats were randomly divided into a control group and a test group. According to Uyghur medicine theory, the test group of rats were given wet cold diet (seeds of spinach and parsley, 24 hours) in a cold (6 °C) and humid (85%-95%, 10 hours) environment for 40 days to establish the rat model of abnormal balgam syndrome. 1H MR based metabonomic analysis of serum was performed. Data was analyzed using Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) software. RESULTS: Compared with the control group, the serum components including glutamate, phenylalanine, tyrosine, citric acid, β-hydrocxy butyrate, acetoacetate, pyruvic acid and creatine were decreased, while the glucose, lactic acid, low density lipoprotein and very low density lipoprotein were increased in the test group (P<0.05). CONCLUSION: The low energy production and consumption in the rat model of abnormal balgam syndrome suggests that the dysfunctional metabolisms of three major nutrients might be the molecular basis for the abnormal balgam syndrome. PMID: 25652368 [PubMed - indexed for MEDLINE]

Related Articles Chemical imaging of latent fingerprints by mass spectrometry based on laser activated electron tunneling. Anal Chem. 2015 Mar 3;87(5):2693-701 Authors: Tang X, Huang L, Zhang W, Zhong H Abstract Identification of endogenous and exogenous chemicals contained in latent fingerprints is important for forensic science in order to acquire evidence of criminal identities and contacts with specific chemicals. Mass spectrometry has emerged as a powerful technique for such applications without any derivatization or fluorescent tags. Among these techniques, MALDI (Matrix Assisted Laser Desorption Ionization) provides small beam size but has interferences with MALDI matrix materials, which cause ion suppressions as well as limited spatial resolution resulting from uneven distribution of MALDI matrix crystals with different sizes. LAET (Laser Activated Electron Tunneling) described in this work offers capabilities for chemical imaging through electron-directed soft ionization. A special film of semiconductors has been designed for collection of fingerprints. Nanoparticles of bismuth cobalt zinc oxide were compressed on a conductive metal substrate (Al or Cu sticky tape) under 10 MPa pressure. Resultant uniform thin films provide tight and shining surfaces on which fingers are impressed. Irradiation of ultraviolet laser pulses (355 nm) on the thin film instantly generates photoelectrons that can be captured by adsorbed organic molecules and subsequently cause electron-directed ionization and fragmentation. Imaging of latent fingerprints is achieved by visualization of the spatial distribution of these molecular ions and structural information-rich fragment ions. Atomic electron emission together with finely tuned laser beam size improve spatial resolution. With the LAET technique, imaging analysis not only can identify physical shapes but also reveal endogenous metabolites present in females and males, detect contacts with prohibited substances, and resolve overlapped latent fingerprints. PMID: 25647159 [PubMed - indexed for MEDLINE]

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Related Articles Impact of kinetic isotope effects in isotopic studies of metabolic systems. BMC Syst Biol. 2015;9(1):64 Authors: Millard P, Portais JC, Mendes P Abstract BACKGROUND: Isotope labeling experiments (ILEs) are increasingly used to investigate the functioning of metabolic systems. Some enzymes are subject to kinetic isotope effects (KIEs) which modulate reaction rates depending on the isotopic composition of their substrate(s). KIEs may therefore affect both the propagation of isotopes through metabolic networks and their operation, and ultimately jeopardize the biological value of ILEs. However, the actual impact of KIEs on metabolism has never been investigated at the system level. RESULTS: First, we developed a framework which integrates KIEs into kinetic and isotopic models of metabolism, thereby accounting for their system-wide effects on metabolite concentrations, metabolic fluxes, and isotopic patterns. Then, we applied this framework to assess the impact of KIEs on the central carbon metabolism of Escherichia coli in the context of (13)C-ILEs, under different situations commonly encountered in laboratories. Results showed that the impact of KIEs strongly depends on the label input and on the variable considered but is significantly lower than expected intuitively from measurements on isolated enzymes. The global robustness of both the metabolic operation and isotopic patterns largely emerge from intrinsic properties of metabolic networks, such as the distribution of control across the network and bidirectional isotope exchange. CONCLUSIONS: These results demonstrate the necessity of investigating the impact of KIEs at the level of the entire system, contradict previous hypotheses that KIEs would have a strong effect on isotopic distributions and on flux determination, and strengthen the biological value of (13)C-ILEs. The proposed modeling framework is generic and can be used to investigate the impact of all the isotopic tracers ((2)H, (13)C, (15)N, (18)O, etc.) on different isotopic datasets and metabolic systems. By allowing the integration of isotopic and metabolomics data collected under stationary and/or non-stationary conditions, it may also assist interpretations of ILEs and facilitate the development of more accurate kinetic models with improved explicative and predictive capabilities. PMID: 26410690 [PubMed - as supplied by publisher]

Related Articles High-throughput approaches to unravel hepatitis C virus-host interactions. Virus Res. 2015 Sep 24; Authors: Colpitts CC, El-Saghire H, Pochet N, Schuster C, Baumert TF Abstract Hepatitis C virus (HCV) remains a major global health burden, with more than 130 million individuals chronically infected and at risk for the development of hepatocellular carcinoma (HCC). The recent clinical licensing of direct-acting antivirals enables viral cure. However, limited access to therapy and treatment failure in patient subgroups warrants a continuing effort to develop complementary antiviral strategies. Furthermore, once fibrosis is established, curing HCV infection does not eliminate the risk for HCC. High-throughput approaches and screens have enabled the investigation of virus-host interactions on a genome-wide scale. Gain- and loss-of-function screens have identified essential host-dependency factors in the HCV viral life cycle, such as host cell entry factors or regulatory factors for viral replication and assembly. Network analyses of systems-scale data sets provided a comprehensive view of the cellular state following HCV infection, thus improving our understanding of the virus-induced responses of the target cell. Interactome, metabolomics and gene expression studies identified dysregulated cellular processes potentially contributing to HCV pathogenesis and HCC. Drug screens using chemical libraries led to the discovery of novel antivirals. Here, we review the contribution of high-throughput approaches for the investigation of virus-host interactions, viral pathogenesis and drug discovery. PMID: 26410623 [PubMed - as supplied by publisher]

Related Articles Vitamin D metabolite profiling using liquid chromatography-tandem mass spectrometry (LC-MS/MS). J Steroid Biochem Mol Biol. 2015 Sep 24; Authors: Jones G, Kaufmann M Abstract Liquid chromatography tandem mass spectrometry (LC-MS/MS) has emerged as the latest technology to be used to assay the metabolites of vitamin D. The method uses molecular mass as a detection technique after straightforward extraction and chromatography steps. LC-MS/MS assay provides a level of accuracy and reproducibility not seen before with other methods and is beginning to rival antibody-based methods in terms of sensitivity and convenience. Methods for detection of underivatized and DMEQ-TAD derivatized vitamin D metabolites are evaluated. Sensitivity is improved by 10-100 fold with derivatization and allows for the simultaneous assay of multiple vitamin D metabolites, a process termed vitamin D metabolite profiling. Clinical and research applications of vitamin D metabolite profiling are discussed. PMID: 26409684 [PubMed - as supplied by publisher]

Metabolic switch during adipogenesis: From branched chain amino acid catabolism to lipid synthesis. Arch Biochem Biophys. 2015 Sep 23; Authors: Halama A, Horsch M, Kastenmüller G, Möller G, Kumar P, Prehn C, Laumen H, Hauner H, Hrabĕ de Angelis M, Beckers J, Suhre K, Adamski J Abstract Fat cell metabolism has an impact on body homeostasis and its proper function. Nevertheless, the knowledge about simultaneous metabolic processes, which occur during adipogenesis and in mature adipocytes, is limited. Identification of key metabolic events associated with fat cell metabolism could be beneficial in the field of novel drug development, drug repurposing, as well as for the discovery of patterns predicting obesity risk. The main objective of our work was to provide comprehensive characterization of metabolic processes occurring during adipogenesis and in mature adipocytes. In order to globally determine crucial metabolic pathways involved in fat cell metabolism, metabolomics and transcriptomics approaches were applied. We observed significantly regulated metabolites correlating with significantly regulated genes at different stages of adipogenesis. We identified the synthesis of phosphatidylcholines, the metabolism of even and odd chain fatty acids, as well as the catabolism of branched chain amino acids (BCAA; leucine, isoleucine and valine) as key regulated pathways. Our further analysis led to identification of an enzymatic switch comprising the enzymes Hmgcs2 (3-hydroxy-3-methylglutaryl-CoA synthase) and Auh (AU RNA binding protein/enoyl-CoA hydratase) which connects leucine degradation with cholesterol synthesis and which is strongly regulated during adipogenesis. In addition, propionyl-CoA, a product of isoleucine degradation, was identified as a putative substrate for odd chain fatty acid synthesis. The uncovered crosstalk's between BCAA and lipid metabolism during adipogenesis might contribute to the understanding of molecular mechanisms of obesity and have potential implications in obesity prediction. PMID: 26408941 [PubMed - as supplied by publisher]