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A review of the pharmaceutical exposome in aquatic fauna.
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A review of the pharmaceutical exposome in aquatic fauna.
Environ Pollut. 2018 Apr 10;239:129-146
Authors: Miller TH, Bury NR, Owen SF, MacRae JI, Barron LP
Abstract
Pharmaceuticals have been considered 'contaminants of emerging concern' for more than 20 years. In that time, many laboratory studies have sought to identify hazard and assess risk in the aquatic environment, whilst field studies have searched for targeted candidates and occurrence trends using advanced analytical techniques. However, a lack of a systematic approach to the detection and quantification of pharmaceuticals has provided a fragmented literature of serendipitous approaches. Evaluation of the extent of the risk for the plethora of human and veterinary pharmaceuticals available requires the reliable measurement of trace levels of contaminants across different environmental compartments (water, sediment, biota - of which biota has been largely neglected). The focus on pharmaceutical concentrations in surface waters and other exposure media have therefore limited both the characterisation of the exposome in aquatic wildlife and the understanding of cause and effect relationships. Here, we compile the current analytical approaches and available occurrence and accumulation data in biota to review the current state of research in the field. Our analysis provides evidence in support of the 'Matthew Effect' and raises critical questions about the use of targeted analyte lists for biomonitoring. We provide six recommendations to stimulate and improve future research avenues.
PMID: 29653304 [PubMed - as supplied by publisher]
Effects of glaucocalyxin A on human liver cancer cells as revealed by GC/MS- and LC/MS-based metabolic profiling.
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Effects of glaucocalyxin A on human liver cancer cells as revealed by GC/MS- and LC/MS-based metabolic profiling.
Anal Bioanal Chem. 2018 Apr 13;:
Authors: Liu Y, Lu S, Zhao L, Dong X, Zhu Z, Jin Y, Chen H, Lu F, Hong Z, Chai Y
Abstract
Studies have documented the potential antitumor activities of glaucocalyxin A (GLA), an ent-kaurene diterpenoid isolated from Rabdosia japonica. However, the metabolic mechanism underlying the antitumor activity of GLA remains largely unknown. The effects of GLA on the metabolome of human liver cancer cells using GC/MS- and LC/MS-based metabolic profiling have been investigated. An untargeted metabolomics approach in conjunction with orthogonal projection to latent structures-discriminant analysis (OPLS-DA) has been developed to characterize the metabolic modifications induced by GLA treatment in human hepatoma cell line SMMC7721. Results demonstrated that cells cultured in the presence or absence of GLA displayed different metabolic profiles: the treatment induced an increased purine metabolism, pyrimidine metabolism, and sphingolipid metabolism and a decreased amino acid metabolism. At the same time, GLA treatment induced cell apoptosis and cell cycle arrested at G2/M phase in a dose-dependent manner. In addition, two representative apoptosis-inducing cytotoxic agents were selected as positive control drugs to validate the reasonableness and accuracy of our metabolomic investigation on GLA. The study displayed a systemic metabolic alteration induced by GLA treatment, showing the impaired physiological activity of SMMC7721 cells, which also indicated anti-proliferative and apoptotic effects of GLA. In the meantime, GC/MS- and LC/MS-based metabolomics applied to cell culture enhanced our current understanding of the metabolic response to GLA treatment and its mechanism; such an approach could be transferred to study the mechanism of other anticancer drugs. Graphical abstract A systemic metabolic alteration induced by glaucocalyxin A (GLA) treatment of SMMC-7721 cells.
PMID: 29651531 [PubMed - as supplied by publisher]
Antiseptic Activity of Ethnomedicinal Xuebijing Revealed by the Metabolomics Analysis Using UHPLC-Q-Orbitrap HRMS.
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Antiseptic Activity of Ethnomedicinal Xuebijing Revealed by the Metabolomics Analysis Using UHPLC-Q-Orbitrap HRMS.
Front Pharmacol. 2018;9:300
Authors: Zuo L, Zhou L, Xu T, Li Z, Liu L, Shi Y, Kang J, Gao G, Du S, Sun Z, Zhang X
Abstract
Xuebijing (XBJ) injection is an ethnomedicinal formula that has been widely used in the therapy of sepsis in China. However, the underlying theraputic mechanisms remain uninvestigated. In this research, a metabolomic method based on UHPLC-Q-Orbitrap HRMS was applied to make a holistic evaluation of XBJ on septic rats which were induced by the classical cecal ligation and puncture (CLP) operation. The plasma metabolic changes were profiled and evaluated by multivariate analytical (MVA) methods. In the results, a total of 41 differential metabolites were identified between CLP-operated group and sham-operated group, which were mainly involved in amino acid metabolism and lipid metabolism. After pathway analysis, it was finally discovered that the majority of the influenced metabolic pathways caused by sepsis mainly involved in energy metabolism, oxidative stress, and inflammation metabolism. When intervened by XBJ injection, 32 of the 41 disordered metabolites had been adjusted in reverse, which suggested that XBJ could mediate the abnormal metabolic pathways synergistically. In conclusion, the present study systematically investigated the efficacy and its underlying therapeutic mechanisms of XBJ on sepsis, while offering a new insight for the subsequent relevant exploration of other Chinese medicine at the same time.
PMID: 29651245 [PubMed]
Psychrotolerant Sphingobacterium kitahiroshimense LT-2 Isolated from Dhundi Glacier, Himachal Pradesh: Origin Prediction and Future Application.
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Psychrotolerant Sphingobacterium kitahiroshimense LT-2 Isolated from Dhundi Glacier, Himachal Pradesh: Origin Prediction and Future Application.
Indian J Microbiol. 2018 Jun;58(2):234-238
Authors: Sharma S, Chatterjee S
Abstract
A psychrotolerant bacterium, isolated from Dhundi Glacier, Himachal Pradesh (India) was identified as Sphingobacterium kitahiroshimense LT-2 on the basis of biochemical, molecular and phylogenetic analysis. Sphingobacterium kitahiroshimense was first reported from Japan and was isolated from the city of Kitahiroshima, Hokkaido, Japan. In this report we have discussed about the origin of our strain and predicted that air masses and dust associated microbial cells transportation phenomena may be applicable for the origin of this species in this region. Enzymes and secondary metabolites secreted by the genus Sphingobacterium have enormous potentiality regarding their biotechnological application. Preliminary study of our strain based on metabolic profiling through HPLC showed many new metabolites were secreted by the bacterium when grown in presence of different sugar medium at 28 °C. As far as our knowledge this is the first report about Sphingobacterium species isolated from this region. This preliminary finding will help to draw an idea about the bacterial population in this Himalayan Glaciers (in HP) as well as biotechnological application of this strain can be explored further.
PMID: 29651184 [PubMed]
Percutaneous Closure of Left Atrial Appendage significantly affects Lipidome Metabolism.
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Percutaneous Closure of Left Atrial Appendage significantly affects Lipidome Metabolism.
Sci Rep. 2018 Apr 12;8(1):5894
Authors: Yücel G, Behnes M, Barth C, Wenke A, Sartorius B, Mashayekhi K, Yazdani B, Bertsch T, Rusnak J, Saleh A, Hoffmann U, Fastner C, Lang S, Zhou X, Sattler K, Borggrefe M, Akin I
Abstract
Patients with non-valvular atrial fibrillation (AF) and a high risk for oral anticoagulation can be treated by percutaneous implantation of left atrial appendage occlusion devices (LAAC) to reduce the risk of cardio-embolic stroke. This study evaluates whether LAAC may influence lipid metabolism, which has never been investigated before. Patients with successful LAAC were included consecutively. Venous peripheral blood samples of patients were collected immediately before (T0, baseline) and 6 months after (T1, mid-term) LAAC. A targeted metabolomics approach based on electrospray ionization liquid chromatography-mass spectrometry (ESI-LC-MS/MS) and MS/MS measurements was performed. A total of 34 lipids revealed a significant change from baseline to mid-term follow-up after successful LAAC. Subgroup analysis revealed confounding influence by gender, age, diabetes mellitus type II, body mass index, left ventricular ejection fraction, creatinine and NT-proBNP. After multivariable adjustment within logistic regression models, these 34 lipids were still significantly altered after LAAC. Successful percutaneous LAAC may affect lipid metabolism and thereby may potentially affect pro-atherogenic and cardio-toxic effects.
PMID: 29650978 [PubMed - in process]
Branched-Chain Amino Acids: The Metabolic Link Between Type 2 Diabetes Mellitus and Cardiovascular Disease?
Related Articles
Branched-Chain Amino Acids: The Metabolic Link Between Type 2 Diabetes Mellitus and Cardiovascular Disease?
Circ Genom Precis Med. 2018 Apr;11(4):e002182
Authors: Tuteja S
PMID: 29650772 [PubMed - in process]
A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites.
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A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites.
Nature. 2017 11 30;551(7682):648-652
Authors: Dodd D, Spitzer MH, Van Treuren W, Merrill BD, Hryckowian AJ, Higginbottom SK, Le A, Cowan TM, Nolan GP, Fischbach MA, Sonnenburg JL
Abstract
The human gut microbiota produces dozens of metabolites that accumulate in the bloodstream, where they can have systemic effects on the host. Although these small molecules commonly reach concentrations similar to those achieved by pharmaceutical agents, remarkably little is known about the microbial metabolic pathways that produce them. Here we use a combination of genetics and metabolic profiling to characterize a pathway from the gut symbiont Clostridium sporogenes that generates aromatic amino acid metabolites. Our results reveal that this pathway produces twelve compounds, nine of which are known to accumulate in host serum. All three aromatic amino acids (tryptophan, phenylalanine and tyrosine) serve as substrates for the pathway, and it involves branching and alternative reductases for specific intermediates. By genetically manipulating C. sporogenes, we modulate serum levels of these metabolites in gnotobiotic mice, and show that in turn this affects intestinal permeability and systemic immunity. This work has the potential to provide the basis of a systematic effort to engineer the molecular output of the gut bacterial community.
PMID: 29168502 [PubMed - indexed for MEDLINE]
A metabolite-GWAS (mGWAS) approach to unveil chronic kidney disease progression.
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A metabolite-GWAS (mGWAS) approach to unveil chronic kidney disease progression.
Kidney Int. 2017 06;91(6):1274-1276
Authors: Zhang G, Saito R, Sharma K
Abstract
In this issue, McMahon et al. report that, by combining phenotypic, metabolomic, and genetic data, they could better detect chronic kidney disease at the early stages and provide insight into its pathobiology. The most significant findings of the study are that several urinary metabolites (e.g., glycine and histidine) were identified as early risk factors for chronic kidney disease, and metabolites with genomewide association study analysis identified associations of urinary metabolites (i.e., lysine and NG-monomethyl-l-arginine) with single-nucleotide polymorphisms of SLC7A9.
PMID: 28501300 [PubMed - indexed for MEDLINE]
Metabolomics-guided investigations of unintended effects of the expression of the hydroxycinnamoyl quinate hydroxycinnamoyltransferase (hqt1) gene from Cynara cardunculus var. scolymus in Nicotiana tabacum cell cultures.
Metabolomics-guided investigations of unintended effects of the expression of the hydroxycinnamoyl quinate hydroxycinnamoyltransferase (hqt1) gene from Cynara cardunculus var. scolymus in Nicotiana tabacum cell cultures.
Plant Physiol Biochem. 2018 Apr 05;127:287-298
Authors: Mudau SP, Steenkamp PA, Piater LA, De Palma M, Tucci M, Madala NE, Dubery IA
Abstract
Chlorogenic acids (CGAs) are phenolic compounds biosynthesized in the phenylpropanoid pathway, with hydroxycinnamoyl quinate hydroxycinnamoyltransferase (HQT) as the key enzyme. Variation of CGAs has been noted in different plants, with globe artichoke (Cynara cardunculus var. scolymus L.) producing high amounts and a diverse spectrum of CGAs in its leaves. In the current study, the effect of overexpression of the hqt1 transgene from globe artichoke in tobacco was evaluated at the metabolome level. Here, metabolomic approaches based on ultra-high performance liquid chromatography coupled to mass spectrometry, together with chemometric models such as principal component analysis and orthogonal partial least square discriminant analysis, were employed to evaluate altered metabolic changes due to hqt1 overexpression. CGA profiles (caffeoylquinic acids: 3-CQA, 4-CQA and 5-CQA; p-coumaroylquinic acids: 4-pCoQA and 5-pCoQA; and 4,5-di-caffeoylquinic acid) of transgenic tobacco cell cultures were detected at lower concentrations than in the wild type. Interestingly, the cells were found to rather accumulate, as an unintended effect, abscisic acid - and benzoic acid derivatives. The results suggest that insertion of hqt1 in tobacco, and overexpression in undifferentiated cells, led to rechannelling of the phenylpropanoid pathway to accumulate benzoic acids. These findings proved to be contrary to the results shown elsewhere in leaf tissues, thus indicating differential metabolic control and regulation in the undifferentiated cell culture system.
PMID: 29649745 [PubMed - as supplied by publisher]
Differential release of cell-signaling metabolites by male and female bovine embryos cultured in vitro.
Differential release of cell-signaling metabolites by male and female bovine embryos cultured in vitro.
Theriogenology. 2018 Apr 05;114:180-184
Authors: Gómez E, Carrocera S, Martin D, Herrero P, Canela N, Muñoz M
Abstract
Male and female early bovine embryos show dimorphic transcription that impacts metabolism. Individual release of metabolites was examined in a 24h single culture medium from Day-6 male and female morulae that developed to Day-7 expanded blastocysts. Embryos were produced in vitro, fertilized with a single bull and cultured in SOFaaci+6 g/L BSA. The embryonic sex was identified (amelogenin gene amplification). Embryos (N = 10 males and N = 10 females) and N = 6 blank samples (i.e. SOFaaci+6 g/L BSA incubated with no embryos) were collected from 3 replicates. Metabolome was analyzed by UHPLC-TOF-MS in spent culture medium. After tentative identification, N = 13 metabolites significantly (P < 0.05; ANOVA) differed in their concentrations between male and female embryos, although N = 10 of these metabolites showed heterogeneity (Levene's test; P > 0.05). LysoPC(15:0) was the only metabolite found at higher concentration in females (fold change [FC] male to female = 0.766). FC of metabolites more abundant in male culture medium (N = 12) varied from 1.069 to 1.604. Chemical taxonomy grouped metabolites as amino-acids and related compounds (DL-2 aminooctanoic acid, arginine, 5-hydroxy-l-tryptophan, and palmitoylglycine); lipids (2-hexenoylcarnitine; Lauroyl diethanolamide; 5,6 dihydroxyprostaglandin F1a; LysoPC(15:0); DG(14:0/14:1(9Z)/0:0) and triterpenoid); endogenous amine ((S)-N-Methylsalsolinol/(R)-N-Methylsalsolinol); n-acyl-alpha-hexosamine (N-acetyl-alpha-d-galactosamine 1-phosphate); and dUMP, a product of pyrimidine metabolism. Among the compounds originally contained in CM, female embryos significantly depleted more arginine than males and blank controls (P < 0.001). Male and female embryos induce different concentrations of metabolites with potential signaling effects. The increased abundance of metabolites released from males is consistent with the higher metabolic activity attributed to such blastocysts.
PMID: 29649720 [PubMed - as supplied by publisher]
Potential role of "omics" technique in prenatal diagnosis of congenital heart defects.
Potential role of "omics" technique in prenatal diagnosis of congenital heart defects.
Clin Chim Acta. 2018 Apr 09;:
Authors: Chen L, Guan J, Wei Q, Yuan Z, Zhang M
Abstract
Congenital heart defect (CHD) is one of the most common birth defects and is the leading cause of neonatal death. Currently, there are no biomarkers available for prenatal diagnosis of CHD. Clinical strategies to diagnose CHD mostly depend on fetal echocardiography. Recent advances in "omics" techniques have opened up new possibilities for biomarker discoveries. In this review, we discuss recent advances in prenatal detection of CHD using biomarkers obtained by "omics" approaches, including genomics, proteomics, metabolomics, and others. There is great potential in obtaining various kinds of parameters using "omics" studies to facilitate early and accurate diagnosis of CHD.
PMID: 29649453 [PubMed - as supplied by publisher]
Multi-Omics Research Trends in Sepsis: A Bibliometric, Comparative Analysis Between the United States, the European Union 28 Member States, and China.
Multi-Omics Research Trends in Sepsis: A Bibliometric, Comparative Analysis Between the United States, the European Union 28 Member States, and China.
OMICS. 2018 Mar;22(3):190-197
Authors: Evangelatos N, Satyamoorthy K, Levidou G, Bauer P, Brand H, Kouskouti C, Lehrach H, Brand A
Abstract
"-Omics" research is in transition with the recent rise of multi-omics technology platforms. Integration of "-omics" and multi-omics research is of high priority in sepsis, a heterogeneous syndrome that is widely recognized as a global health burden and a priority biomedical funding field. We report here an original study on bibliometric trends in the use of "-omics" technologies, and multi-omics approaches in particular, in sepsis research in three (supra)national settings, the United States, the European Union 28 Member States (EU-28), and China. Using a 5-year longitudinal bibliometric study design from 2011 to 2015, we analyzed the sepsis-related research articles in English language that included at least one or multi-omics technologies in publicly available form in Medline (free full texts). We found that the United States has had the lead (almost one-third of publications) in the inclusion of an "-omics" or multi-omics technology in sepsis within the study period. However, both China and the EU-28 displayed a significant increase in the number of publications that employed one or more types of "-omics" research (p < 0.005), while the EU-28 displayed a significant increase especially in multi-omics research articles in sepsis (p < 0.05). Notably, more than half of the multi-omics research studies in the sepsis knowledge domain had a university or government/state funding source. Among the multi-omics research publications in sepsis, the combination of genomics and transcriptomics was the most frequent (40.5%), followed by genomics and proteomics (20.4%). We suggest that the lead of the United States in the field of "-omics" and multi-omics research in sepsis is likely at stake, with both the EU-28 and China rapidly increasing their research capacity. Moreover, "triple omics" that combine genomics, proteomics, and metabolomics analyses appear to be uncommon in sepsis, and yet much needed for triangulation of systems science data. These observations have implications for "-omics" technology policy and global research funding strategic foresight.
PMID: 29649387 [PubMed - in process]
NAFLD risk alleles in PNPLA3, TM6SF2, GCKR, and LYPLAL1 show divergent metabolic effects.
NAFLD risk alleles in PNPLA3, TM6SF2, GCKR, and LYPLAL1 show divergent metabolic effects.
Hum Mol Genet. 2018 Apr 10;:
Authors: Sliz E, Sebert S, Würtz P, Kangas AJ, Soininen P, Lehtimäki T, Kähönen M, Viikari J, Männikkö M, Ala-Korpela M, Raitakari OT, Kettunen J
Abstract
Fatty liver has been associated with unfavourable metabolic changes in circulation. To provide insights in fatty liver related metabolic deviations, we compared metabolic association profile of fatty liver versus metabolic association profiles of genotypes increasing the risk of non-alcoholic fatty liver disease (NAFLD). The cross-sectional associations of ultrasound-ascertained fatty liver with 123 metabolic measures were determined in 1,810 (Nfatty liver=338) individuals aged 34-49 years from The Cardiovascular Risk in Young Finns Study. The association profiles of NAFLD risk alleles in PNPLA3, TM6SF2, GCKR, and LYPLAL1 with the corresponding metabolic measures were obtained from a publicly available metabolomics GWAS including up to 24,925 Europeans. The risk alleles showed different metabolic effects: PNPLA3 rs738409-G, the strongest genetic NAFLD risk factor, did not associate with metabolic changes. Metabolic effects of GCKR rs1260326-T were comparable in many respects to the fatty liver associations. Metabolic effects of LYPLAL1 rs12137855-C were similar, but statistically less robust, to the effects of GCKR rs1260326-T. TM6SF2 rs58542926-T displayed opposite metabolic effects when compared with the fatty liver associations. The metabolic effects of the risk alleles highlight heterogeneity of the molecular pathways leading to fatty liver and suggest that the fatty liver related changes in the circulating lipids and metabolites may vary depending on the underlying pathophysiological mechanism. Despite the robust cross-sectional associations on population level, the present results showing neutral or cardioprotective metabolic effects for some of the NAFLD risk alleles advocate that hepatic lipid accumulation by itself may not increase the level of circulating lipids or other metabolites.
PMID: 29648650 [PubMed - as supplied by publisher]
LipidPedia: a comprehensive lipid knowledgebase.
LipidPedia: a comprehensive lipid knowledgebase.
Bioinformatics. 2018 Apr 10;:
Authors: Kuo TC, Tseng YJ
Abstract
Motivation: Lipids are divided into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, saccharolipids, sterols, prenol lipids and polyketides. Fatty acyls and glycerolipids are commonly used as energy storage, whereas glycerophospholipids, sphingolipids, sterols and saccharolipids are common used as components of cell membranes. Lipids in fatty acyls, glycerophospholipids, sphingolipids and sterols classes play important roles in signaling. Although more than 36 million lipids can be identified or computationally generated, no single lipid database provides comprehensive information on lipids. Furthermore, the complex systematic or common names of lipids make the discovery of related information challenging.
Results: Here, we present LipidPedia, a comprehensive lipid knowledgebase. The content of this database is derived from integrating annotation data with full-text mining of 3,923 lipids and more than 400,000 annotations of associated diseases, pathways, functions, and locations that are essential for interpreting lipid functions and mechanisms from over 1,400,000 scientific publications. Each lipid in LipidPedia also has its own entry containing a text summary curated from the most frequently cited diseases, pathways, genes, locations, functions, lipids and experimental models in the biomedical literature. LipidPedia aims to provide an overall synopsis of lipids to summarize lipid annotations and provide a detailed listing of references for understanding complex lipid functions and mechanisms.
Availability: LipidPedia is available at http://lipidpedia.cmdm.tw.
Contact: yjtseng@csie.ntu.edu.tw.
Supplementary information: Supplementary data are available at Bioinformatics online.
PMID: 29648583 [PubMed - as supplied by publisher]
Metabolic phenotyping of malnutrition during the first 1000 days of life.
Metabolic phenotyping of malnutrition during the first 1000 days of life.
Eur J Nutr. 2018 Apr 11;:
Authors: Mayneris-Perxachs J, Swann JR
Abstract
Nutritional restrictions during the first 1000 days of life can impair or delay the physical and cognitive development of the individual and have long-term consequences for their health. Metabolic phenotyping (metabolomics/metabonomics) simultaneously measures a diverse range of low molecular weight metabolites in a sample providing a comprehensive assessment of the individual's biochemical status. There are a growing number of studies applying such approaches to characterize the metabolic derangements induced by various forms of early-life malnutrition. This includes acute and chronic undernutrition and specific micronutrient deficiencies. Collectively, these studies highlight the diverse and dynamic metabolic disruptions resulting from various forms of nutritional deficiencies. Perturbations were observed in many pathways including those involved in energy, amino acid, and bile acid metabolism, the metabolic interactions between the gut microbiota and the host, and changes in metabolites associated with gut health. The information gleaned from such studies provides novel insights into the mechanisms linking malnutrition with developmental impairments and assists in the elucidation of candidate biomarkers to identify individuals at risk of developmental shortfalls. As the metabolic profile represents a snapshot of the biochemical status of an individual at a given time, there is great potential to use this information to tailor interventional strategies specifically to the metabolic needs of the individual.
PMID: 29644395 [PubMed - as supplied by publisher]
Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and Magnitude of Tumor-Specific CD8+ T Cell Response.
Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and Magnitude of Tumor-Specific CD8+ T Cell Response.
J Immunol. 2018 Apr 11;:
Authors: Khong H, Volmari A, Sharma M, Dai Z, Imo CS, Hailemichael Y, Singh M, Moore DT, Xiao Z, Huang XF, Horvath TD, Hawke DH, Overwijk WW
Abstract
Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that an excessively long duration of Ag presentation critically reduced the quantity and quality of vaccination-induced T cell responses and subsequent antitumor efficacy. In this study, using a murine model and tumor cell lines, we studied l-tyrosine amino acid-based microparticles as a peptide vaccine adjuvant with a short-term Ag depot function for the induction of tumor-specific T cells. l-Tyrosine microparticles did not induce dendritic cell maturation, and their adjuvant activity was not mediated by inflammasome activation. Instead, prolonged Ag presentation in vivo translated into increased numbers and antitumor activity of vaccination-induced CD8+ T cells. Indeed, prolonging Ag presentation by repeated injection of peptide in saline resulted in an increase in T cell numbers similar to that observed after vaccination with peptide/l-tyrosine microparticles. Our results show that the duration of Ag presentation is critical for optimal induction of antitumor T cells, and can be manipulated through vaccine formulation.
PMID: 29643190 [PubMed - as supplied by publisher]
Robust volcano plot: identification of differential metabolites in the presence of outliers.
Robust volcano plot: identification of differential metabolites in the presence of outliers.
BMC Bioinformatics. 2018 Apr 11;19(1):128
Authors: Kumar N, Hoque MA, Sugimoto M
Abstract
BACKGROUND: The identification of differential metabolites in metabolomics is still a big challenge and plays a prominent role in metabolomics data analyses. Metabolomics datasets often contain outliers because of analytical, experimental, and biological ambiguity, but the currently available differential metabolite identification techniques are sensitive to outliers.
RESULTS: We propose a kernel weight based outlier-robust volcano plot for identifying differential metabolites from noisy metabolomics datasets. Two numerical experiments are used to evaluate the performance of the proposed technique against nine existing techniques, including the t-test and the Kruskal-Wallis test. Artificially generated data with outliers reveal that the proposed method results in a lower misclassification error rate and a greater area under the receiver operating characteristic curve compared with existing methods. An experimentally measured breast cancer dataset to which outliers were artificially added reveals that our proposed method produces only two non-overlapping differential metabolites whereas the other nine methods produced between seven and 57 non-overlapping differential metabolites.
CONCLUSION: Our data analyses show that the performance of the proposed differential metabolite identification technique is better than that of existing methods. Thus, the proposed method can contribute to analysis of metabolomics data with outliers. The R package and user manual of the proposed method are available at https://github.com/nishithkumarpaul/Rvolcano .
PMID: 29642836 [PubMed - in process]
Pasture Feeding Changes the Bovine Rumen and Milk Metabolome.
Pasture Feeding Changes the Bovine Rumen and Milk Metabolome.
Metabolites. 2018 Apr 06;8(2):
Authors: O'Callaghan TF, Vázquez-Fresno R, Serra-Cayuela A, Dong E, Mandal R, Hennessy D, McAuliffe S, Dillon P, Wishart DS, Stanton C, Ross RP
Abstract
The purpose of this study was to examine the effects of two pasture feeding systems-perennial ryegrass (GRS) and perennial ryegrass and white clover (CLV)-and an indoor total mixed ration (TMR) system on the (a) rumen microbiome; (b) rumen fluid and milk metabolome; and (c) to assess the potential to distinguish milk from different feeding systems by their respective metabolomes. Rumen fluid was collected from nine rumen cannulated cows under the different feeding systems in early, mid and late lactation, and raw milk samples were collected from ten non-cannulated cows in mid-lactation from each of the feeding systems. The microbiota present in rumen liquid and solid portions were analysed using 16S rRNA gene sequencing, while ¹H-NMR untargeted metabolomic analysis was performed on rumen fluid and raw milk samples. The rumen microbiota composition was not found to be significantly altered by any feeding system in this study, likely as a result of a shortened adaptation period (two weeks' exposure time). In contrast, feeding system had a significant effect on both the rumen and milk metabolome. Increased concentrations of volatile fatty acids including acetic acid, an important source of energy for the cow, were detected in the rumen of TMR and CLV-fed cows. Pasture feeding resulted in significantly higher concentrations of isoacids in the rumen. The ruminal fluids of both CLV and GRS-fed cows were found to have increased concentrations of p-cresol, a product of microbiome metabolism. CLV feeding resulted in increased rumen concentrations of formate, a substrate compound for methanogenesis. The TMR feeding resulted in significantly higher rumen choline content, which contributes to animal health and milk production, and succinate, a product of carbohydrate metabolism. Milk and rumen-fluids were shown to have varying levels of dimethyl sulfone in each feeding system, which was found to be an important compound for distinguishing between the diets. CLV feeding resulted in increased concentrations of milk urea. Milk from pasture-based feeding systems was shown to have significantly higher concentrations of hippuric acid, a potential biomarker of pasture-derived milk. This study has demonstrated that ¹H-NMR metabolomics coupled with multivariate analysis is capable of distinguishing both rumen-fluid and milk derived from cows on different feeding systems, specifically between indoor TMR and pasture-based diets used in this study.
PMID: 29642378 [PubMed]
Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB.
Related Articles
Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB.
Microbiologyopen. 2017 Aug;6(4):
Authors: Fazli M, Rybtke M, Steiner E, Weidel E, Berthelsen J, Groizeleau J, Bin W, Zhi BZ, Yaming Z, Kaever V, Givskov M, Hartmann RW, Eberl L, Tolker-Nielsen T
Abstract
Knowledge about the molecular mechanisms that are involved in the regulation of biofilm formation is essential for the development of biofilm-control measures. It is well established that the nucleotide second messenger cyclic diguanosine monophosphate (c-di-GMP) is a positive regulator of biofilm formation in many bacteria, but more knowledge about c-di-GMP effectors is needed. We provide evidence that c-di-GMP, the alternative sigma factor RpoN (σ54), and the enhancer-binding protein BerB play a role in biofilm formation of Burkholderia cenocepacia by regulating the production of a biofilm-stabilizing exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive transcriptional regulator. An increased level of the BerA protein in turn induces the production of biofilm-stabilizing exopolysaccharide in response to high c-di-GMP levels. Our findings imply that the production of biofilm exopolysaccharide in B. cenocepacia is regulated through a cascade involving two consecutive transcription events that are both activated by c-di-GMP. This type of regulation may allow tight control of the expenditure of cellular resources.
PMID: 28419759 [PubMed - indexed for MEDLINE]