PubMed

Related Articles PathVisio 3: an extendable pathway analysis toolbox. PLoS Comput Biol. 2015 Feb;11(2):e1004085 Authors: Kutmon M, van Iersel MP, Bohler A, Kelder T, Nunes N, Pico AR, Evelo CT Abstract PathVisio is a commonly used pathway editor, visualization and analysis software. Biological pathways have been used by biologists for many years to describe the detailed steps in biological processes. Those powerful, visual representations help researchers to better understand, share and discuss knowledge. Since the first publication of PathVisio in 2008, the original paper was cited more than 170 times and PathVisio was used in many different biological studies. As an online editor PathVisio is also integrated in the community curated pathway database WikiPathways. Here we present the third version of PathVisio with the newest additions and improvements of the application. The core features of PathVisio are pathway drawing, advanced data visualization and pathway statistics. Additionally, PathVisio 3 introduces a new powerful extension systems that allows other developers to contribute additional functionality in form of plugins without changing the core application. PathVisio can be downloaded from http://www.pathvisio.org and in 2014 PathVisio 3 has been downloaded over 5,500 times. There are already more than 15 plugins available in the central plugin repository. PathVisio is a freely available, open-source tool published under the Apache 2.0 license (http://www.apache.org/licenses/LICENSE-2.0). It is implemented in Java and thus runs on all major operating systems. The code repository is available at http://svn.bigcat.unimaas.nl/pathvisio. The support mailing list for users is available on https://groups.google.com/forum/#!forum/wikipathways-discuss and for developers on https://groups.google.com/forum/#!forum/wikipathways-devel. PMID: 25706687 [PubMed - indexed for MEDLINE]

Related Articles Cancer and the gut microbiota: an unexpected link. Sci Transl Med. 2015 Jan 21;7(271):271ps1 Authors: Zitvogel L, Galluzzi L, Viaud S, Vétizou M, Daillère R, Merad M, Kroemer G Abstract Changes in the interactions among the gut microbiota, intestinal epithelium, and host immune system are associated with many diseases, including cancer. We discuss how environmental factors infuence this cross-talk during oncogenesis and tumor progression and how manipulations of the gut microbiota might improve the clinical activity of anticancer agents. PMID: 25609166 [PubMed - indexed for MEDLINE]

Related Articles A U-system approach for predicting metabolic behaviors and responses based on an alleged metabolic reaction network. BMC Syst Biol. 2014;8 Suppl 5:S4 Authors: Sriyudthsak K, Sawada Y, Chiba Y, Yamashita Y, Kanaya S, Onouchi H, Fujiwara T, Naito S, Voit EO, Shiraishi F, Hirai MY Abstract BACKGROUND: Progress in systems biology offers sophisticated approaches toward a comprehensive understanding of biological systems. Yet, computational analyses are held back due to difficulties in determining suitable model parameter values from experimental data which naturally are subject to biological fluctuations. The data may also be corrupted by experimental uncertainties and sometimes do not contain all information regarding variables that cannot be measured for technical reasons. RESULTS: We show here a streamlined approach for the construction of a coarse model that allows us to set up dynamic models with minimal input information. The approach uses a hybrid between a pure mass action system and a generalized mass action (GMA) system in the framework of biochemical systems theory (BST) with rate constants of 1, normal kinetic orders of 1, and -0.5 and 0.5 for inhibitory and activating effects, named Unity (U)-system. The U-system model does not necessarily fit all data well but is often sufficient for predicting metabolic behavior of metabolites which cannot be simultaneously measured, identifying inconsistencies between experimental data and the assumed underlying pathway structure, as well as predicting system responses to a modification of gene or enzyme. The U-system approach was validated with small, generic systems and implemented to model a large-scale metabolic reaction network of a higher plant, Arabidopsis. The dynamic behaviors obtained by predictive simulations agreed with actually available metabolomic time-series data, identified probable errors in the experimental datasets, and estimated probable behavior of unmeasurable metabolites in a qualitative manner. The model could also predict metabolic responses of Arabidopsis with altered network structures due to genetic modification. CONCLUSIONS: The U-system approach can effectively predict metabolic behaviors and responses based on structures of an alleged metabolic reaction network. Thus, it can be a useful first-line tool of data analysis, model diagnostics and aid the design of next-step experiments. PMID: 25559748 [PubMed - indexed for MEDLINE]

Related Articles Transgenic American chestnuts show enhanced blight resistance and transmit the trait to T1 progeny. Plant Sci. 2014 Nov;228:88-97 Authors: Newhouse AE, Polin-McGuigan LD, Baier KA, Valletta KE, Rottmann WH, Tschaplinski TJ, Maynard CA, Powell WA Abstract American chestnut (Castanea dentata) is a classic example of a native keystone species that was nearly eradicated by an introduced fungal pathogen. This report describes progress made toward producing a fully American chestnut tree with enhanced resistance to the blight fungus (Cryphonectria parasitica). The transgenic American chestnut 'Darling4,' produced through an Agrobacterium co-transformation procedure to express a wheat oxalate oxidase gene driven by the VspB vascular promoter, shows enhanced blight resistance at a level intermediate between susceptible American chestnut and resistant Chinese chestnut (Castanea mollissima). Enhanced resistance was identified first with a leaf-inoculation assay using young chestnuts grown indoors, and confirmed with traditional stem inoculations on 3- and 4-year-old field-grown trees. Pollen from 'Darling4' and other events was used to produce transgenic T1 seedlings, which also expressed the enhanced resistance trait in leaf assays. Outcrossed transgenic seedlings have several advantages over tissue-cultured plantlets, including increased genetic diversity and faster initial growth. This represents a major step toward the restoration of the majestic American chestnut. PMID: 25438789 [PubMed - indexed for MEDLINE]

Related Articles The ability of bilirubin in identifying smokers with higher risk of lung cancer: a large cohort study in conjunction with global metabolomic profiling. Clin Cancer Res. 2015 Jan 1;21(1):193-200 Authors: Wen CP, Zhang F, Liang D, Wen C, Gu J, Skinner H, Chow WH, Ye Y, Pu X, Hildebrandt MA, Huang M, Chen CH, Hsiung CA, Tsai MK, Tsao CK, Lippman SM, Wu X Abstract PURPOSE: We aimed to identify serum metabolites as potential valuable biomarkers for lung cancer and to improve risk stratification in smokers. EXPERIMENTAL DESIGN: We performed global metabolomic profiling followed by targeted validation of individual metabolites in a case-control design of 386 lung cancer cases and 193 matched controls. We then validated bilirubin, which consistently showed significant differential levels in cases and controls, as a risk marker for lung cancer incidence and mortality in a large prospective cohort composed of 425,660 participants. RESULTS: Through global metabolomic profiling and following targeted validation, bilirubin levels consistently showed a statistically significant difference among healthy controls and lung cancer cases. In the prospective cohort, the inverse association was only seen in male smokers, regardless of smoking pack-years and intensity. Compared with male smokers in the highest bilirubin group (>1 mg/dL), those in the lowest bilirubin group (<0.75 mg/dL) had 55% and 66% increase in risks of lung cancer incidence and mortality, respectively. For every 0.1 mg/dL decrease of bilirubin, the risks for lung cancer incidence and mortality increased by 5% and 6% in male smokers, respectively (both P < 0.001). There was a significant interaction between low serum bilirubin level and smoking on lung cancer risk (Pinteraction = 0.001). CONCLUSION: Low levels of serum bilirubin are associated with higher risks of lung cancer incidence and mortality in male smokers and can be used to identify higher risk smokers for lung cancer. PMID: 25336700 [PubMed - indexed for MEDLINE]

Related Articles Sulfate-reducing bacteria mediate thionation of diphenylarsinic acid under anaerobic conditions. Biodegradation. 2015 Feb;26(1):29-38 Authors: Guan L, Shiiya A, Hisatomi S, Fujii K, Nonaka M, Harada N Abstract Diphenylarsinic acid (DPAA) is often found as a toxic intermediate metabolite of diphenylchloroarsine or diphenylcyanoarsine that were produced as chemical warfare agents and were buried in soil after the World Wars. In our previous study Guan et al. (J Hazard Mater 241-242:355-362, 2012), after application of sulfate and carbon sources, anaerobic transformation of DPAA in soil was enhanced with the production of diphenylthioarsinic acid (DPTAA) as a main metabolite. This study aimed to isolate and characterize anaerobic soil microorganisms responsible for the metabolism of DPAA. First, we obtained four microbial consortia capable of transforming DPAA to DPTAA at a high transformation rate of more than 80% after 4 weeks of incubation. Sequencing for the bacterial 16S rRNA gene clone libraries constructed from the consortia revealed that all the positive consortia contained Desulfotomaculum acetoxidans species. In contrast, the absence of dissimilatory sulfite reductase gene (dsrAB) which is unique to sulfate-reducing bacteria was confirmed in the negative consortia showing no DPAA reduction. Finally, strain DEA14 showing transformation of DPAA to DPTAA was isolated from one of the positive consortia. The isolate was assigned to D. acetoxidans based on the partial 16S rDNA sequence analysis. Thionation of DPAA was also carried out in a pure culture of a known sulfate-reducing bacterial strain, Desulfovibrio aerotolerans JCM 12613(T). These facts indicate that sulfate-reducing bacteria are microorganisms responsible for the transformation of DPAA to DPTAA under anaerobic conditions. PMID: 25228086 [PubMed - indexed for MEDLINE]

Related Articles Negative prognostic value of high levels of intracellular poly (ADP-ribose) in non-small cell lung cancer. Ann Oncol. 2015 Sep 19; Authors: Michels J, Adam J, Goubar A, Obrist F, Damotte D, Robin A, Alifano M, Vitale I, Olaussen KA, Girard P, Cremer I, Castedo M, Soria JC, Kroemer G Abstract BACKGROUND: Cisplatin-resistant non-small cell lung cancer (NSCLC) cells are often characterized by alterations in vitamin B-related metabolic processes, including the overexpression and hyperactivation of poly(ADP-ribose) polymerase 1 (PARP1) and the down-regulation of pyridoxal kinase (PDXK), correlating with elevated apoptosis resistance. Low PDXK expression is an established negative prognostic factor in NSCLC. PATIENTS AND METHODS: We determined by immunohistochemistry the expression of PARP1 and the level of its product, poly(ADP-ribose) (PAR) in two independent cohorts of patients with resected NSCLC. RESULTS: Intratumoral high levels (above median) of PAR (but not PARP1 protein levels) had a negative prognostic impact in both the training (92 stage I subjects) and validation (133 stage I and II subjects) cohorts, as determined by univariate and multivariate analyses. The simultaneous assessment of PAR and PDXK protein levels improved risk stratification. CONCLUSION: NSCLC patients with high intratumoral PARP1 activity (i.e., elevated PAR levels above median) and low PDXK expression (below median) had, a dismal prognosis, while patients with low PARP1 activity and high PDXK expression had a favourable outcome. Altogether, these results underscore the clinical potential and possible therapeutic relevance of these biomarkers. PMID: 26387143 [PubMed - as supplied by publisher]

Systematic analysis of rice (Oryza sativa) metabolic responses to herbivory. Plant Cell Environ. 2015 Sep 19; Authors: Alamgir KM, Hojo Y, Christeller JT, Fukumoto K, Isshiki R, Shinya T, Baldwin IT, Galis I Abstract Plants defend against attack from herbivores by direct and indirect defense mechanisms mediated by the accumulation of phytoalexins and release of volatile signals, respectively. While the defensive arsenals of some plants, such as tobacco and Arabidopsis are well known, most of rice's (Oryza sativa) defense metabolites and their effectiveness against herbivores remain uncharacterized. Here, we used a non-biased metabolomics approach to identify many novel herbivory-regulated metabolic signatures in rice. Most were up-regulated by herbivore attack while only a few were suppressed. Two of the most prominent up-regulated signatures were characterized as phenolamides (PAs), p-coumaroylputrescine and feruloylputrescine. PAs accumulated in response to attack by both chewing insects, i.e. feeding of the lawn armyworm (Spodoptera mauritia) and the rice skipper (Parnara guttata) larvae, and the attack of the sucking insect, the brown planthopper (Nilaparvata lugens, BPH). In bioassays, BPH insects feeding on 15% sugar solution containing p-coumaroylputrescine or feruloylputrescine, at concentrations similar to those elicited by heavy BPH attack in rice, had a higher mortality compared to those feeding on sugar diet alone. Our results highlight PAs as a rapidly expanding new group of plant defense metabolites that are elicited by herbivore attack, and deter herbivores in rice and other plants. PMID: 26386366 [PubMed - as supplied by publisher]

RhizoFlowCell system reveals early effects of micropollutants on aquatic plant rhizosphere. Environ Pollut. 2015 Sep 16;207:205-210 Authors: Mynampati KC, Lee YJ, Wijdeveld A, Reuben S, Samavedham L, Kjelleberg S, Swarup S Abstract In aquatic systems, one of the non-destructive ways to quantify toxicity of contaminants to plants is to monitor changes in root exudation patterns. In aquatic conditions, monitoring and quantifying such changes are currently challenging because of dilution of root exudates in water phase and lack of suitable instrumentation to measure them. Exposure to pollutants would not only change the plant exudation, but also affect the microbial communities that surround the root zone, thereby changing the metabolic profiles of the rhizosphere. This study aims at developing a device, the RhizoFlowCell, which can quantify metabolic response of plants, as well as changes in the microbial communities, to give an estimate of the stress to which the rhizosphere is exposed. The usefulness of RhizoFlowCell is demonstrated using naphthalene as a test pollutant. Results show that RhizoFlowCell system is useful in quantifying the dynamic metabolic response of aquatic rhizosphere to determine ecosystem health. PMID: 26386206 [PubMed - as supplied by publisher]

Metabolic responses to Lactobacillus plantarum contamination or bacteriophage treatment in Saccharomyces cerevisiae using a GC-MS-based metabolomics approach. World J Microbiol Biotechnol. 2015 Sep 18; Authors: Cui FX, Zhang RM, Liu HQ, Wang YF, Li H Abstract Bacteriophage can be used as a potential alternative agent for controlling Lactobacillus plantarum contamination during bioethanol production. However, how Saccharomyces cerevisiae respond against contaminative L. plantarum or added bacteriophage remains to be fully understood. In this study, gas chromatography-mass spectrometry and a multivariate analysis were employed to investigate the intracellular biochemical changes in S. cerevisiae cells that were elicited by L. plantarum contamination or bacteriophage treatment. The intracellular metabolite profiles originating from different groups were unique and could be distinguished with the aid of principal component analysis. Moreover, partial least-squares-discriminant analysis revealed a group classification and pairwise discrimination, and 13 differential metabolites with variable importance in the projection value greater than 1 were identified. The metabolic relevance of these compounds in the response of S. cerevisiae to L. plantarum contamination or bacteriophage treatment was discussed. Besides generating lactic acid and competing for nutrients or living space, L. plantarum contamination might also inhibit the growth of S. cerevisiae through regulating the glycolysis in S. cerevisiae. Moreover, increased concentrations of monounsaturated fatty acids secondary to bacteriophage treatment might lead to more membrane fluidity and promote the cell viability of S. cerevisiae. PMID: 26385547 [PubMed - as supplied by publisher]

Vaginal microbiome and metabolome highlight specific signatures of bacterial vaginosis. Eur J Clin Microbiol Infect Dis. 2015 Sep 18; Authors: Vitali B, Cruciani F, Picone G, Parolin C, Donders G, Laghi L Abstract In this study, we sought to find novel bacterial and metabolic hallmarks for bacterial vaginosis (BV). We studied the vaginal microbiome and metabolome of vaginal fluids from BV-affected patients (n = 43) and healthy controls (n = 37) by means of an integrated approach based on quantitative polymerase chain reaction (qPCR) and proton nuclear magnetic resonance ((1)H-NMR). The correlations between the clinical condition and vaginal bacterial communities were investigated by principal component analysis (PCA). To define the metabolomics signatures of BV, 100 discriminant analysis by projection on latent structure (PLS-DA) models were calculated. Bacterial signatures distinguishing the health condition and BV were identified by qPCR. Lactobacillus crispatus strongly featured the healthy vagina, while increased concentrations of Prevotella, Atopobium and Mycoplasma hominis specifically marked the infection. (1)H-NMR analysis has led to the identification and quantification of 17 previously unreported molecules. BV was associated with changes in the concentration of metabolites belonging to the families of amines, organic acids, short chain fatty acids, amino acids, nitrogenous bases and monosaccharides. In particular, maltose, kynurenine and NAD(+) primarily characterised the healthy status, while nicotinate, malonate and acetate were the best metabolic hallmarks of BV. This study helps to better understand the role of the vaginal microbiota and metabolome in the development of BV infection. We propose a molecular approach for the diagnosis of BV based on quantitative detection in the vaginal fluids of Atopobium, Prevotella and M. hominis, and nicotinate, malonate and acetate by combining qPCR and (1)H-NMR. PMID: 26385347 [PubMed - as supplied by publisher]

Metabolic responses of the isopod Porcellionides pruinosus to nickel exposure assessed by (1)H NMR metabolomics. J Proteomics. 2015 Sep 15; Authors: Ferreira NG, Saborano R, Morgado R, Cardoso DN, Rocha CM, Soares AM, Loureiro S, Duarte IF PMID: 26385004 [PubMed - as supplied by publisher]

Physiological changes due to mild cooling in healthy lean males of white Caucasian and South Asian descent: a metabolomics study. Arch Biochem Biophys. 2015 Sep 15; Authors: Nahon KJ, Boon MR, Bakker LE, Prehn C, Adamski J, Jazet IM, van Dijk KW, Rensen PC, Mook-Kanamori DO Abstract During mild cold exposure, non-shivering thermogenesis increases to maintain core body temperature by increasing utilization of substrates, especially fatty acids (FA), ultimately affecting lipid-associated metabolites. We aimed to investigate whether mild cooling induces changes in other metabolites and whether this response differs between white Caucasians and South Asians, who have a disadvantageous metabolic phenotype. 12 lean male Dutch white Caucasians and 12 matched Dutch South Asians were exposed to mild cold. Before and after 100 minutes exposure, serum samples were collected for analysis of 163 metabolites and 27 derived parameters using high throughput metabolomics. The overall response to mild cooling between both ethnicities was not different, therefore the data were pooled. After Bonferroni correction, mild cooling significantly changed 44 of 190 (23%) metabolic parameters. Specifically, cooling increased 19 phosphatidylcholine (PC) species, only those containing very long chain FAs, and increased the total class of PC containing mono-unsaturated FAs (+12.5%). Furthermore, cooling increased 10 sphingomyelin species as well as the amino acids glutamine (+18.7%), glycine (+11.6%) and histidine (+10.6%), and decreased short-chain (C3 and C4) acylcarnitines (-17.1% and -19.4%, respectively). In conclusion, mild cooling elicits substantial effects on serum metabolites in healthy males, irrespective of white Caucasian or South Asian ethnicity. PMID: 26384768 [PubMed - as supplied by publisher]

Related Articles Exploring the Process of Energy Generation in Pathophysiology by Targeted Metabolomics: Performance of a Simple and Quantitative Method. J Am Soc Mass Spectrom. 2015 Sep 17; Authors: Riera-Borrull M, Rodríguez-Gallego E, Hernández-Aguilera A, Luciano F, Ras R, Cuyàs E, Camps J, Segura-Carretero A, Menendez JA, Joven J, Fernández-Arroyo S Abstract Abnormalities in mitochondrial metabolism and regulation of energy balance contribute to human diseases. The consequences of high fat and other nutrient intake, and the resulting acquired mitochondrial dysfunction, are essential to fully understand common disorders, including obesity, cancer, and atherosclerosis. To simultaneously and noninvasively measure and quantify indirect markers of mitochondrial function, we have developed a method based on gas chromatography coupled to quadrupole-time of flight mass spectrometry and an electron ionization interface, and validated the system using plasma from patients with peripheral artery disease, human cancer cells, and mouse tissues. This approach was used to increase sensibility in the measurement of a wide dynamic range and chemical diversity of multiple intermediate metabolites used in energy metabolism. We demonstrate that our targeted metabolomics method allows for quick and accurate identification and quantification of molecules, including the measurement of small yet significant biological changes in experimental samples. The apparently low process variability required for its performance in plasma, cell lysates, and tissues allowed a rapid identification of correlations between interconnected pathways. Our results suggest that delineating the process of energy generation by targeted metabolomics can be a valid surrogate for predicting mitochondrial dysfunction in biological samples. Importantly, when used in plasma, targeted metabolomics should be viewed as a robust and noninvasive source of biomarkers in specific pathophysiological scenarios. Graphical Abstract ᅟ. PMID: 26383735 [PubMed - as supplied by publisher]

Related Articles Changes in Brain Metallome/Metabolome Pattern due to a Single i.v. Injection of Manganese in Rats. PLoS One. 2015;10(9):e0138270 Authors: Neth K, Lucio M, Walker A, Zorn J, Schmitt-Kopplin P, Michalke B Abstract Exposure to high concentrations of Manganese (Mn) is known to potentially induce an accumulation in the brain, leading to a Parkinson related disease, called manganism. Versatile mechanisms of Mn-induced brain injury are discussed, with inactivation of mitochondrial defense against oxidative stress being a major one. So far, studies indicate that the main Mn-species entering the brain are low molecular mass (LMM) compounds such as Mn-citrate. Applying a single low dose MnCl2 injection in rats, we observed alterations in Mn-species pattern within the brain by analysis of aqueous brain extracts by size-exclusion chromatography-inductively coupled plasma mass spectrometry (SEC-ICP-MS). Additionally, electrospray ionization-ion cyclotron resonance-Fourier transform-mass spectrometry (ESI-ICR/FT-MS) measurement of methanolic brain extracts revealed a comprehensive analysis of changes in brain metabolisms after the single MnCl2 injection. Major alterations were observed for amino acid, fatty acid, glutathione, glucose and purine/pyrimidine metabolism. The power of this metabolomic approach is the broad and detailed overview of affected brain metabolisms. We also correlated results from the metallomic investigations (Mn concentrations and Mn-species in brain) with the findings from metabolomics. This strategy might help to unravel the role of different Mn-species during Mn-induced alterations in brain metabolism. PMID: 26383269 [PubMed - as supplied by publisher]

Related Articles Integrated isotope-assisted metabolomics and (13)C metabolic flux analysis reveals metabolic flux redistribution for high glucoamylase production by Aspergillus niger. Microb Cell Fact. 2015;14(1):147 Authors: Lu H, Liu X, Huang M, Xia J, Chu J, Zhuang Y, Zhang S, Noorman H Abstract BACKGROUND: Aspergillus niger is widely used for enzyme production and achievement of high enzyme production depends on the comprehensive understanding of cell's metabolic regulation mechanisms. RESULTS: In this paper, we investigate the metabolic differences and regulation mechanisms between a high glucoamylase-producing strain A. niger DS03043 and its wild-type parent strain A. niger CBS513.88 via an integrated isotope-assisted metabolomics and (13)C metabolic flux analysis approach. We found that A. niger DS03043 had higher cell growth, glucose uptake, and glucoamylase production rates but lower oxalic acid and citric acid secretion rates. In response to above phenotype changes, A. niger DS03043 was characterized by an increased carbon flux directed to the oxidative pentose phosphate pathway in contrast to reduced flux through TCA cycle, which were confirmed by consistent changes in pool sizes of metabolites. A higher ratio of ATP over AMP in the high producing strain might contribute to the increase in the PP pathway flux as glucosephosphate isomerase was inhibited at higher ATP concentrations. A. niger CBS513.88, however, was in a higher redox state due to the imbalance of NADH regeneration and consumption, resulting in the secretion of oxalic acid and citric acid, as well as the accumulation of intracellular OAA and PEP, which may in turn result in the decrease in the glucose uptake rate. CONCLUSIONS: The application of integrated metabolomics and (13)C metabolic flux analysis highlights the regulation mechanisms of energy and redox metabolism on flux redistribution in A. niger. Graphical abstract An integrated isotope-assisted metabolomics and (13)C metabolic flux analysis was was firstly systematically performed in A. niger. In response to enzyme production, the metabolic flux in A. niger DS03043 (high-producing) was redistributed, characterized by an increased carbon flux directed to the oxidative pentose phosphate pathway as well as an increased pool size of pentose. The consistency in (13)C metabolic flux analysis and metabolites quantification indicated that an imbalance of NADH formation and consumption led to the accumulation and secretion of organic acids in A. niger CBS513.88 (wild-type). PMID: 26383080 [PubMed - as supplied by publisher]

Related Articles Learning from other diseases: protection and pathology in chronic fungal infections. Semin Immunopathol. 2015 Sep 17; Authors: Zelante T, Pieraccini G, Scaringi L, Aversa F, Romani L Abstract Fungal commensals coexist in a complex milieu of bacteria within the human body. An increased understanding of the importance of microbiota in shaping the host's immune and metabolic activities has rendered fungal interactions with their hosts more complex than previously appreciated. Metagenomics has revealed the complex interactions between fungal and bacterial commensals that, either directly or through the participation of the host immune system, impact on immune homeostasis at mucosal surfaces that, in turn, lead to secondary fungal infections. Metabolomics has captured the dialogue between the mammalian host and its microbiota. It appears that the host tryptophan catabolic enzyme, indoleamine 2,3-dioxygenase 1 (IDO1) plays a dominant role in the interplay between tryptophan catabolism by microbial communities, the host's own pathway of metabolite production, and the activation of the aryl hydrocarbon receptor (AhR)/IL-22 axis, eventually impacting on mucosal immune homeostasis and host/fungal symbiosis. Thus, the regulatory loop involving AhR and IDO1 may be exploited for the development of multi-pronged host- and microbiota-directed therapeutic approaches for mucosal and systemic fungal diseases. PMID: 26382631 [PubMed - as supplied by publisher]

Related Articles A robust and efficient method for estimating enzyme complex abundance and metabolic flux from expression data. Comput Biol Chem. 2015 Sep 1; Authors: Barker BE, Sadagopan N, Wang Y, Smallbone K, Myers CR, Xi H, Locasale JW, Gu Z Abstract A major theme in constraint-based modeling is unifying experimental data, such as biochemical information about the reactions that can occur in a system or the composition and localization of enzyme complexes, with high-throughput data including expression data, metabolomics, or DNA sequencing. The desired result is to increase predictive capability and improve our understanding of metabolism. The approach typically employed when only gene (or protein) intensities are available is the creation of tissue-specific models, which reduces the available reactions in an organism model, and does not provide an objective function for the estimation of fluxes. We develop a method, flux assignment with LAD (least absolute deviation) convex objectives and normalization (FALCON), that employs metabolic network reconstructions along with expression data to estimate fluxes. In order to use such a method, accurate measures of enzyme complex abundance are needed, so we first present an algorithm that addresses quantification of complex abundance. Our extensions to prior techniques include the capability to work with large models and significantly improved run-time performance even for smaller models, an improved analysis of enzyme complex formation, the ability to handle large enzyme complex rules that may incorporate multiple isoforms, and either maintained or significantly improved correlation with experimentally measured fluxes. FALCON has been implemented in MATLAB and ATS, and can be downloaded from: https://github.com/bbarker/FALCON. ATS is not required to compile the software, as intermediate C source code is available. FALCON requires use of the COBRA Toolbox, also implemented in MATLAB. PMID: 26381164 [PubMed - as supplied by publisher]

Related Articles Metabolic youth in middle age - predicting ageing in Caenorhabditis elegans using metabolomics. J Proteome Res. 2015 Sep 18; Authors: Davies SK, Bundy JG, Leroi AM Abstract Many mutations and allelic variants are known that influence the rate at which animals age. But when in life do such variants diverge from normal patterns of ageing? And is this divergence visible in their physiologies? To investigate these questions we have used 1H NMR spectroscopy to study how the metabolome of the nematode Caenorhabditis elegans changes as it grows older. We identify a series of metabolic changes that, collectively, predict the age of wild-type worms. We then show that long-lived mutant daf-2(m41) worms are metabolically youthful compared to wild-type worms - but that this relative youth only appears in middle age. Finally, we show that metabolic age predicts the timing and magnitude of differences in age-specific mortality between these strains. Thus the future mortality of these two genotypes can be predicted long before most of the worms die. PMID: 26381038 [PubMed - as supplied by publisher]

Related Articles Non-invasive assessment of in-vitro embryo quality to improve transfer success. Reprod Biomed Online. 2015 Aug 12; Authors: Rødgaard T, Heegaard PM, Callesen H Abstract Although IVF has been performed routinely for many years to help couples with fertility problems and in relation to modern breeding of farm animals, pregnancy rates after transfer to a recipient have not improved during the last decade. Early prediction of the viability of in-vitro developed embryos before the transfer to a recipient still remains challenging. Presently, the predominant non-invasive technique for selecting viable embryos is based on morphology, where parameters such as rates of cleavage and blastocyst formation as well as developmental kinetics are evaluated mostly subjectively. The simple morphological approach is, however, inadequate for the prediction of embryo quality, and several studies have focused on developing new non-invasive methods using molecular approaches based particularly on proteomics, metabolomics and most recently small non-coding RNA, including microRNA. This review outlines the potential of several non-invasive in-vitro methods based on analysis of spent embryo culture medium. PMID: 26380864 [PubMed - as supplied by publisher]