PubMed

In Vivo Studies in Rhodospirillum rubrum Indicate that Ribulose-1,5,bisphosphate carboxylase/oxygenase (Rubisco) Catalyzes Two Obligatorily Required and Physiologically Significant Reactions for Distinct Carbon and Sulfur Metabolic Pathways. J Biol Chem. 2015 Oct 28; Authors: Dey S, North JA, Sriram J, Evans BS, Tabita FR Abstract All organisms possess fundamental metabolic pathways to insure that needed carbon and sulfur compounds are provided to the cell in the proper chemical form and oxidation state. For most organisms capable of using CO2 as sole source of carbon, ribulose-1,5-bisphosphate (RuBP) carboxylase/oxy-genase (Rubisco) catalyzes primary carbon dioxide assimilation. In addition, sulfur salvage pathways are necessary to insure that key sulfur-containing compounds are both available and, where necessary, detoxified in the cell. Using knockout mutations and metabolomics in the bacterium Rhodospirillum rubrum, we show here that Rubisco concurrently catalyzes key and essential reactions for seemingly unrelated but physiologically essential central carbon and sulfur salvage metabolic pathways of the cell. In this study, complementation and mutagenesis studies indicated representatives of all extant known functional Rubisco forms found in nature are capable of simultaneously catalyzing reactions required for both CO2-dependent growth as well as growth using 5-methylthioadenosine (MTA) as sole sulfur source under anaerobic photosynthetic conditions. Moreover, specific inactivation of the CO2 fixation reaction did not affect the ability of Rubisco to support anaerobic MTA metabolism, suggesting that the active site of Rubisco has evolved to insure that this enzyme maintains both key functions. Thus, despite the coevolution of both functions, the active site of this protein may be differentially modified to affect only one of its key functions. PMID: 26511314 [PubMed - as supplied by publisher]

Quantitative profiling of oxylipins in plasma and atherosclerotic plaques of hypercholesterolemic rabbits. Anal Bioanal Chem. 2015 Oct 28; Authors: Bojic LA, McLaren DG, Harms AC, Hankemeier T, Dane A, Wang SP, Rosa R, Previs SF, Johns DG, Castro-Perez JM Abstract Oxylipins are oxidation products of polyunsaturated fatty acids (PUFAs) that affect a broad range of physiological processes, including cell proliferation, inflammation, inflammation resolution, and vascular function. Moreover, oxylipins are readily detectable in plasma, and certain subsets of oxylipins have been detected in human atherosclerotic lesions. Taken together, we set out to produce a detailed quantitative assessment of plasma and plaque oxylipins in a widely used model of atherosclerosis, to identify potential biomarkers of disease progression. We administered regular chow or regular chow supplemented with 0.5 % cholesterol (HC) to male New Zealand white rabbits for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our targeted lipidomic analyses of oxylipins on plaques isolated from rabbits fed the HC diet detected 34 oxylipins, 28 of which were in compliance with our previously established quality control acceptance criteria. The arachidonic acid (AA) metabolite derived from the COX pathway, 6-keto-PGF1α was the most abundant plaque oxylipin, followed by the linoleic acid (LA) metabolites 9-HODE, 13-HODE and 9,12,13-TriHOME and the arachidonic acid (AA)-derivatives 11-HETE and 12-HETE. We additionally found that the most abundant oxylipins in plasma were three of the five most abundant oxylipins in plaque, namely 11-HETE, 13-HODE, and 9-HODE. The studies reported here make the first step towards a comprehensive characterization of oxylipins as potentially translatable biomarkers of atherosclerosis. PMID: 26511226 [PubMed - as supplied by publisher]

Metabolic profiles of male meat eaters, fish eaters, vegetarians, and vegans from the EPIC-Oxford cohort. Am J Clin Nutr. 2015 Oct 28; Authors: Schmidt JA, Rinaldi S, Ferrari P, Carayol M, Achaintre D, Scalbert A, Cross AJ, Gunter MJ, Fensom GK, Appleby PN, Key TJ, Travis RC Abstract BACKGROUND: Human metabolism is influenced by dietary factors and lifestyle, environmental, and genetic factors; thus, men who exclude some or all animal products from their diet might have different metabolic profiles than meat eaters. OBJECTIVE: We aimed to investigate differences in concentrations of 118 circulating metabolites, including acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, and sphingolipids related to lipid, protein, and carbohydrate metabolism between male meat eaters, fish eaters, vegetarians, and vegans from the Oxford arm of the European Prospective Investigation into Cancer and Nutrition. DESIGN: In this cross-sectional study, concentrations of metabolites were measured by mass spectrometry in plasma from 379 men categorized according to their diet group. Differences in mean metabolite concentrations across diet groups were tested by using ANOVA, and a false discovery rate-controlling procedure was used to account for multiple testing. Principal component analysis was used to investigate patterns in metabolic profiles. RESULTS: Concentrations of 79% of metabolites differed significantly by diet group. In the vast majority of these cases, vegans had the lowest concentration, whereas meat eaters most often had the highest concentrations of the acylcarnitines, glycerophospholipids, and sphingolipids, and fish eaters or vegetarians most often had the highest concentrations of the amino acids and a biogenic amine. A clear separation between patterns in the metabolic profiles of the 4 diet groups was seen, with vegans being noticeably different from the other groups because of lower concentrations of some glycerophospholipids and sphingolipids. CONCLUSIONS: Metabolic profiles in plasma could effectively differentiate between men from different habitual diet groups, especially vegan men compared with men who consume animal products. The difference in metabolic profiles was mainly explained by the lower concentrations of glycerophospholipids and sphingolipids in vegans. PMID: 26511225 [PubMed - as supplied by publisher]

Silibinin-mediated metabolic reprogramming attenuates pancreatic cancer-induced cachexia and tumor growth. Oncotarget. 2015 Oct 16; Authors: Shukla SK, Dasgupta A, Mehla K, Gunda V, Vernucci E, Souchek J, Goode G, King R, Mishra A, Rai I, Nagarajan S, Chaika NV, Yu F, Singh PK Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths in the US. Cancer-associated cachexia is present in up to 80% of PDAC patients and is associated with aggressive disease and poor prognosis. In the present studies we evaluated an anti-cancer natural product silibinin for its effectiveness in targeting pancreatic cancer aggressiveness and the cachectic properties of pancreatic cancer cells and tumors. Our results demonstrate that silibinin inhibits pancreatic cancer cell growth in a dose-dependent manner and reduces glycolytic activity of cancer cells. Our LC-MS/MS based metabolomics data demonstrates that silibinin treatment induces global metabolic reprogramming in pancreatic cancer cells. Silibinin treatment diminishes c-MYC expression, a key regulator of cancer metabolism. Furthermore, we observed reduced STAT3 signaling in silibinin-treated cancer cells. Overexpression of constitutively active STAT3 was sufficient to substantially revert the silibinin-induced downregulation of c-MYC and the metabolic phenotype. Our in vivo investigations demonstrate that silibinin reduces tumor growth and proliferation in an orthotopic mouse model of pancreatic cancer and prevents the loss of body weight and muscle. It also improves physical activity including grip strength and latency to fall in tumor-bearing mice. In conclusion, silibinin-induced metabolic reprogramming diminishes cell growth and cachectic properties of pancreatic cancer cells and animal models. PMID: 26510913 [PubMed - as supplied by publisher]

Ancient Chinese Formula Qiong-Yu-Gao Protects Against Cisplatin-Induced Nephrotoxicity Without Reducing Anti-tumor Activity. Sci Rep. 2015;5:15592 Authors: Teng ZY, Cheng XL, Cai XT, Yang Y, Sun XY, Xu JD, Lu WG, Chen J, Hu CP, Zhou Q, Wang XN, Li SL, Cao P Abstract Cisplatin is a highly effective anti-cancer chemotherapeutic agent; however, its clinical use is severely limited by serious side effects, of which nephrotoxicity is the most important. In this study, we investigated whether Qiong-Yu-Gao (QYG), a popular traditional Chinese medicinal formula described 840 years ago, exhibits protective effects against cisplatin-induced renal toxicity. Using a mouse model of cisplatin-induced renal dysfunction, we observed that pretreatment with QYG attenuated cisplatin-induced elevations in blood urea nitrogen and creatinine levels, ameliorated renal tubular lesions, reduced apoptosis, and accelerated tubular cell regeneration. Cisplatin-mediated elevations in tumor necrosis factor alpha (TNF-α) mRNA, interleukin-1 beta (IL-1β) mRNA, and cyclooxygenase-2 (COX-2) protein in the kidney were also significantly suppressed by QYG treatment. Furthermore, QYG reduced platinum accumulation in the kidney by decreasing the expression of copper transporter 1 and organic cation transporter 2. An in vivo study using implanted Lewis lung cancer cells revealed that concurrent administration of QYG and cisplatin did not alter the anti-tumor activity of cisplatin. Our findings suggest that the traditional Chinese medicinal formula QYG inhibits cisplatin toxicity by several mechanisms that act simultaneously, without compromising its therapeutic efficacy. Therefore, QYG may be useful in the clinic as a protective agent to prevent cisplatin-induced nephrotoxicity. PMID: 26510880 [PubMed - in process]

Metabolomics to explore imidacloprid induced toxicity in the central nervous system of the freshwater snail Lymnaea stagnalis. Environ Sci Technol. 2015 Oct 28; Authors: Tufi S, Stel JM, De Boer J, Lamoree MH, Leonards PE Abstract Modern toxicology is seeking new testing methods to better understand toxicological effects. One of the most concerning chemicals is the neonicotinoid pesticide imidacloprid. Although imidacloprid is designed to target insects, recent studies have shown adverse effects on non-target species. Metabolomics was applied to investigate imidacloprid-induced sublethal toxicity in the CNS of the freshwater snail Lymnaea stagnalis. The snails (n=10 snails) were exposed for 10 days to increasing imidacloprid concentrations (0.1, 1, 10 and 100 µg/L). The comparison between control and exposure groups highlighted the involvement and perturbation of many biological pathways. The levels of several metabolites belonging to different metabolite classes were significantly changed by imidacloprid exposure. A change in the amino acids and nucleotide metabolites like tryptophan, proline, phenylalanine, uridine and guanosine was found. Many fatty acids were down-regulated and the levels of the polyamines, spermidine and putrescine, were found to be increased which is an indication of neuron cell injury. A turnover increase between choline and acetylcholine led us to hypothesize an increase in cholinergic gene expression to overcome imidacloprid binding to the nicotinic acetylcholine receptors. Metabolomics revealed imidacloprid induced metabolic changes at low and environmentally relevant concentration in a non-target species and generated a novel mechanistic hypothesis. PMID: 26509427 [PubMed - as supplied by publisher]

Endothelin-1 Overexpression Improves Renal Function in eNOS Knockout Mice. Cell Physiol Biochem. 2015 Oct 29;37(4):1474-1490 Authors: Tsuprykov O, Chaykovska L, Kretschmer A, Stasch JP, Pfab T, Krause-Relle K, Reichetzeder C, Kalk P, Adamski J, Hocher B Abstract BACKGROUND/AIMS: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. METHODS: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. RESULTS: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpine1, TIMP1, Col1a1, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. CONCLUSION: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in β-oxidation of fatty acids) and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels). PMID: 26509263 [PubMed - as supplied by publisher]

Metabolic profiling reveals potential metabolic markers associated with Hypoxia Inducible Factor-mediated signalling in hypoxic cancer cells. Sci Rep. 2015;5:15649 Authors: Armitage EG, Kotze HL, Allwood JW, Dunn WB, Goodacre R, Williams KJ Abstract Hypoxia inducible factors (HIFs) plays an important role in oxygen compromised environments and therefore in tumour survival. In this research, metabolomics has been applied to study HIFs metabolic function in two cell models: mouse hepatocellular carcinoma and human colon carcinoma, whereby the metabolism has been profiled for a range of oxygen potentials. Wild type cells have been compared to cells deficient in HIF signalling to reveal its effect on cellular metabolism under normal oxygen conditions as well as low oxygen, hypoxic and anoxic environments. Characteristic responses to hypoxia that were conserved across both cell models involved the anti-correlation between 2-hydroxyglutarate, 2-oxoglutarate, fructose, hexadecanoic acid, hypotaurine, pyruvate and octadecenoic acid with 4-hydroxyproline, aspartate, cysteine, glutamine, lysine, malate and pyroglutamate. Further to this, network-based correlation analysis revealed HIF specific pathway responses to each oxygen condition that were also conserved between cell models. From this, 4-hydroxyproline was revealed as a regulating hub in low oxygen survival of WT cells while fructose appeared to be in HIF deficient cells. Pathways surrounding these hubs were built from the direct connections of correlated metabolites that look beyond traditional pathways in order to understand the mechanism of HIF response to low oxygen environments. PMID: 26508589 [PubMed - in process]

Biomarkers in amyotrophic lateral sclerosis: combining metabolomic and clinical parameters to define disease progression. Eur J Neurol. 2015 Oct 28; Authors: Blasco H, Nadal-Desbarats L, Pradat PF, Gordon PH, Madji Hounoum B, Patin F, Veyrat-Durebex C, Mavel S, Beltran S, Emond P, Andres CR, Corcia P Abstract BACKGROUND AND PURPOSE: The objectives of this study were to define the metabolomic profile of cerebrospinal fluid in amyotrophic lateral sclerosis (ALS) patients, to model outcome through combined clinical and metabolomic parameters and independently to validate predictive models. METHODS: In all, 74 consecutive newly diagnosed patients were enrolled into training (Tr, n = 49) and test (Te, n = 25) cohorts. Investigators recorded clinical data and the metabalomic profile of cerebrospinal fluid at baseline was analyzed with (1) H nuclear magnetic resonance spectroscopy. Markers of disease progression, collected in 1-year prospective follow-up, included change in ALS Functional Rating Scale (var_ALSFRS), change in weight (var_weight) and survival time. Stepwise multiple regression selected from metabolomic and clinical parameters to model rate of progression in the Tr cohort. Best fit models were validated independently in the Te cohort. RESULTS: The best-fit statistical models, using both metabolomic and clinical covariates, predicted outcome with 70.8% (var_weight), 72% (var_ALSFRS) and 76% (survival) accuracy in the Te cohort. Models that used metabolomics or clinical data alone predicted outcome less well. Highlighted metabolites are involved in pathophysiological pathways previously described in ALS. CONCLUSION: Cerebrospinal fluid metabolomics can aid in predicting the clinical course of ALS and tap into pathophysiological processes. The precision of predictive models, independently reproduced in this study, is enhanced through inclusion of both metabolomic and clinical parameters. The findings bring the field closer to a clinically meaningful disease marker. PMID: 26508442 [PubMed - as supplied by publisher]

HPLC 2015. Bioanalysis. 2015 Oct 28; Authors: Vries R, Koppen V Abstract The HPLC 2015 Conference was held from 21 to 25 June at the International Conference Center in Geneva, Switzerland. The emphasis of the meeting was around fundamental aspects of separations, sample preparation, novel developments and applications and hyphenation with MS. In this conference report, a selection of highlights of the Conference is given, based on the sessions attended by the authors, and focusing on subjects with possible relevance in the field of drug metabolism and bioanalysis. Selected papers from HPLC 2015 will be published in a virtual special issue of the Journal of Chromatography. PMID: 26508210 [PubMed - as supplied by publisher]

Biomarker-based drug safety assessment in the age of systems pharmacology: from foundational to regulatory science. Biomark Med. 2015 Oct 28; Authors: Zhang C, Hong H, Mendrick DL, Tang Y, Cheng F Abstract Improved biomarker-based assessment of drug safety is needed in drug discovery and development as well as regulatory evaluation. However, identifying drug safety-related biomarkers such as genes, proteins, miRNA and single-nucleotide polymorphisms remains a big challenge. The advances of 'omics' and computational technologies such as genomics, transcriptomics, metabolomics, proteomics, systems biology, network biology and systems pharmacology enable us to explore drug actions at the organ and organismal levels. Computational and experimental systems pharmacology approaches could be utilized to facilitate biomarker-based drug safety assessment for drug discovery and development and to inform better regulatory decisions. In this article, we review the current status and advances of systems pharmacology approaches for the development of predictive models to identify biomarkers for drug safety assessment. PMID: 26506997 [PubMed - as supplied by publisher]

Combined evaluation of LC3B puncta and HMGB1 expression predicts residual risk of relapse after adjuvant chemotherapy in breast cancer. Autophagy. 2015 Oct 3;11(10):1878-90 Authors: Ladoire S, Penault-Llorca F, Senovilla L, Dalban C, Enot D, Locher C, Prada N, Poirier-Colame V, Chaba K, Arnould L, Ghiringhelli F, Fumoleau P, Spielmann M, Delaloge S, Poillot ML, Arveux P, Goubar A, Andre F, Zitvogel L, Kroemer G Abstract In spite of adjuvant chemotherapy, a significant fraction of patients with localized breast cancer (BC) relapse after optimal treatment. We determined the occurrence of cytoplasmic MAP1LC3B/LC3B (microtubule-associated protein 1 light chain 3B)-positive puncta, as well as the presence of nuclear HMGB1 (high mobility group box 1) in cancer cells within surgical BC specimens by immunohistochemistry, first in a test cohort (152 patients) and then in a validation cohort of localized BC patients who all received adjuvant anthracycline-based chemotherapy (1646 patients). Cytoplasmic LC3B(+) puncta inversely correlated with the intensity of SQSTM1 staining, suggesting that a high percentage cells of LC3B(+) puncta reflects increased autophagic flux. After setting optimal thresholds in the test cohort, cytoplasmic LC3B(+) puncta and nuclear HMGB1 were scored as positive in 27.2% and 28.6% of the tumors, respectively, in the validation cohort, while 8.7% were considered as double positive. LC3B(+) puncta or HMGB1 expression alone did not constitute independent prognostic factors for metastasis-free survival (MFS) in multivariate analyses. However, the combined positivity for LC3B(+) puncta and nuclear HMGB1 constituted an independent prognostic factor significantly associated with prolonged MFS (hazard ratio: 0.49 95% confidence interval [0.26-0.89]; P = 0.02), and improved breast cancer specific survival (hazard ratio: 0.21 95% confidence interval [0.05-0.85]; P = 0.029). Subgroup analyses revealed that within patients with poor-prognosis BC, HMGB1(+) LC3B(+) double-positive tumors had a better prognosis than BC that lacked one or both of these markers. Altogether, these results suggest that the combined positivity for LC3B(+) puncta and nuclear HMGB1 is a positive predictor for longer BC survival. PMID: 26506894 [PubMed - in process]

Related Articles Context-specific metabolic network reconstruction of a naphthalene-degrading bacterial community guided by metaproteomic data. Bioinformatics. 2015 Jun 1;31(11):1771-9 Authors: Tobalina L, Bargiela R, Pey J, Herbst FA, Lores I, Rojo D, Barbas C, Peláez AI, Sánchez J, von Bergen M, Seifert J, Ferrer M, Planes FJ Abstract MOTIVATION: With the advent of meta-'omics' data, the use of metabolic networks for the functional analysis of microbial communities became possible. However, while network-based methods are widely developed for single organisms, their application to bacterial communities is currently limited. RESULTS: Herein, we provide a novel, context-specific reconstruction procedure based on metaproteomic and taxonomic data. Without previous knowledge of a high-quality, genome-scale metabolic networks for each different member in a bacterial community, we propose a meta-network approach, where the expression levels and taxonomic assignments of proteins are used as the most relevant clues for inferring an active set of reactions. Our approach was applied to draft the context-specific metabolic networks of two different naphthalene-enriched communities derived from an anthropogenically influenced, polyaromatic hydrocarbon contaminated soil, with (CN2) or without (CN1) bio-stimulation. We were able to capture the overall functional differences between the two conditions at the metabolic level and predict an important activity for the fluorobenzoate degradation pathway in CN1 and for geraniol metabolism in CN2. Experimental validation was conducted, and good agreement with our computational predictions was observed. We also hypothesize different pathway organizations at the organismal level, which is relevant to disentangle the role of each member in the communities. The approach presented here can be easily transferred to the analysis of genomic, transcriptomic and metabolomic data. PMID: 25618865 [PubMed - indexed for MEDLINE]

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2015/10/28PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2015/10/27PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Analysis of Chemical Properties of Edible and Medicinal Ginger by Metabolomics Approach. Biomed Res Int. 2015;2015:671058 Authors: Tanaka K, Arita M, Sakurai H, Ono N, Tezuka Y Abstract In traditional herbal medicine, comprehensive understanding of bioactive constituent is important in order to analyze its true medicinal function. We investigated the chemical properties of medicinal and edible ginger cultivars using a liquid-chromatography mass spectrometry (LC-MS) approach. Our PCA results indicate the importance of acetylated derivatives of gingerol, not gingerol or shogaol, as the medicinal indicator. A newly developed ginger cultivar, Z. officinale cv. Ogawa Umare or "Ogawa Umare" (OG), contains more active ingredients, showing properties as a new resource for the production of herbal medicines derived from ginger in terms of its chemical constituents and rhizome yield. PMID: 26495311 [PubMed - as supplied by publisher]

Related Articles In vitro and in vivo metabolism of N-adamantyl substituted urea-based soluble epoxide hydrolase inhibitors. Biochem Pharmacol. 2015 Oct 19; Authors: Liu JY, Tsai HJ, Morisseau C, Lango J, Hwang SH, Watanabe T, Kim IH, Hammock BD Abstract N,N'-Disubstituted urea-based soluble epoxide hydrolase (sEH) inhibitors are promising therapeutics for hypertension, inflammation, and pain in multiple animal models. The drug absorption and pharmacological efficacy of these inhibitors have been reported extensively. However, the drug metabolism of these inhibitors is not well described. Here we reported the metabolic profile and associated biochemical studies of an N-adamantyl urea-based sEH inhibitor 1-adamantan-1-yl-3-(5-(2-(2-ethoxyethoxy)ethoxy)pentyl)urea (AEPU) in vitro and in vivo. The metabolites of AEPU were identified by interpretation of liquid chromatography-mass chromatography (LC-MS), liquid chromatography-tandem mass spectrometry (LC-MS/MS) and/or NMR. In vitro, AEPU had three major positions for phase I metabolism including oxidations on the adamantyl moiety, urea nitrogen atoms, and cleavage of the polyethylene glycol chain. In a rodent model, the metabolites from the hydroxylation on the adamantyl group and nitrogen atom were existed in blood while the metabolites from cleavage of polyethylene glycol chain were not found in urine. The major metabolite found in rodent urine was 3-(3-adamantyl-ureido)-propanoic acid, a presumably from cleavage and oxidation of the polyethylene glycol moiety. All the metabolites found were active but less potent than AEPU at inhibiting human sEH. Furthermore, cytochrome P450 (CYP) 3A4 was found to be a major enzyme mediating AEPU metabolism. In conclusion, the metabolism of AEPU resulted from oxidation by CYP could be shared with other N-adamantyl-urea-based compounds. These findings suggest possible therapeutic roles for AEPU and new strategies for drug design in this series of possible drugs. PMID: 26494425 [PubMed - as supplied by publisher]

Related Articles Proteomic and metabolomic profiles demonstrate variation among free-living and symbiotic vibrio fischeri biofilms. BMC Microbiol. 2015;15(1):226 Authors: Chavez-Dozal A, Gorman C, Nishiguchi MK Abstract BACKGROUND: A number of bacterial species are capable of growing in various life history modes that enable their survival and persistence in both planktonic free-living stages as well as in biofilm communities. Mechanisms contributing to either planktonic cell or biofilm persistence and survival can be carefully delineated using multiple differential techniques (e.g., genomics and transcriptomics). In this study, we present both proteomic and metabolomic analyses of Vibrio fischeri biofilms, demonstrating the potential for combined differential studies for elucidating life-history switches important for establishing the mutualism through biofilm formation and host colonization. METHODS: The study used a metabolomics/proteomics or "meta-proteomics" approach, referring to the combined protein and metabolic data analysis that bridges the gap between phenotypic changes (planktonic cell to biofilm formation) with genotypic changes (reflected in protein/metabolic profiles). Our methods used protein shotgun construction, followed by liquid chromatography coupled with mass spectrometry (LC-MS) detection and quantification for both free-living and biofilm forming V. fischeri. RESULTS: We present a time-resolved picture of approximately 100 proteins (2D-PAGE and shotgun proteomics) and 200 metabolites that are present during the transition from planktonic growth to community biofilm formation. Proteins involved in stress response, DNA repair damage, and transport appeared to be highly expressed during the biofilm state. In addition, metabolites detected in biofilms correspond to components of the exopolysaccharide (EPS) matrix (sugars and glycerol-derived). Alterations in metabolic enzymes were paralleled by more pronounced changes in concentration of intermediates from the glycolysis pathway as well as several amino acids. CONCLUSIONS: This combined analysis of both types of information (proteins, metabolites) has provided a more complete picture of the biochemical processes of biofilm formation and what determines the switch between the two life history strategies. The reported findings have broad implications for Vibrio biofilm ecology, and mechanisms for successful survival in the host and environment. PMID: 26494154 [PubMed - as supplied by publisher]

Related Articles Metabolome Analyses in Exposome Studies: Profiling Methods for a Vast Chemical Space. Arch Biochem Biophys. 2015 Oct 19; Authors: Athersuch T Abstract Metabolic profiling (metabonomics/metabolomics) is now used routinely as a tool to provide information-rich datasets for biomarker discovery, prompting and augmenting detailed mechanistic studies. The experimental design and focus of any individual study will be reflected in the types of biomarkers that can be detected; toxicological studies will likely focus on markers of response to insult, whereas clinical case-control studies may yield diagnostic markers of disease. Population studies can make use of omics analyses, including metabonomics, to provide mechanistically-relevant markers that link environmental exposures to chronic disease endpoints. In this article, examples of how metabolic profiling has played a key role in molecular epidemiological analyses of chronic disease are presented, and how these reflect different aspects of the causal pathway. A commentary on the nature of metabolome analysis as a complex mixture analysis problem as opposed to a coded, sequence or template problem is provided, alongside an overview of current and future analytical platforms that are being applied to meet this analytical challenge. Epidemiological studies are an important nexus for integrating various measures of the human exposome, and the ubiquity, diversity and functions of small molecule metabolites, represent an important way to link individual exposures, genetics and phenotype. PMID: 26494045 [PubMed - as supplied by publisher]

Related Articles Tubulin cytoskeleton during microsporogenesis in the male-sterile genotype of Allium sativum and fertile Allium ampeloprasum L. Plant Reprod. 2015 Oct 22; Authors: Tchórzewska D, Deryło K, Błaszczyk L, Winiarczyk K Abstract KEY MESSAGE: Microsporogenesis in garlic. The male-sterile Allium sativum (garlic) reproduces exclusively in the vegetative mode, and anthropogenic factors seem to be the cause of the loss of sexual reproduction capability. There are many different hypotheses concerning the causes of male sterility in A. sativum; however, the mechanisms underlying this phenomenon have not been comprehensively elucidated. Numerous attempts have been undertaken to understand the causes of male sterility, but the tubulin cytoskeleton in meiotically dividing cells during microsporogenesis has never been investigated in this species. Using sterile A. sativum genotype L13 and its fertile close relative A. ampeloprasum (leek), we have analysed the distribution of the tubulin cytoskeleton during microsporogenesis. We observed that during karyokinesis and cytokinesis, in both meiotic divisions I and II, the microtubular cytoskeleton in garlic L13 formed configurations that resembled tubulin arrangement typical of monocots. However, the tubulin cytoskeleton in garlic was distinctly poorer (composed of a few MT filaments) compared with that found in meiotically dividing cells in A. ampeloprasum. These differences did not affect the course of karyogenesis, chondriokinesis, and cytokinesis, which contributed to completion of microsporogenesis, but there was no further development of the male gametophyte. At the very beginning of the successive stage of development of fertile pollen grains, i.e. gametogenesis, there were disorders involving the absence of a normal cortical cytoskeleton and dramatically progressive degeneration of the cytoplasm in garlic. Therefore, we suggest that, due to disturbances in cortical cytoskeleton formation at the very beginning of gametogenesis, the intracellular transport governed by the cytoskeleton might be perturbed, leading to microspore decay in the male-sterile garlic genotype. PMID: 26493316 [PubMed - as supplied by publisher]