PubMed

Plasma Metabolic Profiles in Women are Menopause Dependent. PLoS One. 2015;10(11):e0141743 Authors: Ke C, Hou Y, Zhang H, Yang K, Wang J, Guo B, Zhang F, Li H, Zhou X, Li Y, Li K Abstract Menopause is an endocrinological transition that greatly affects health and disease susceptibility in middle-aged and elderly women. To gain new insights into the metabolic process of menopause, plasma metabolic profiles in 115 pre- and post-menopausal women were systematically analyzed by ultra-performance liquid chromatography/mass spectrometry in conjunction with univariate and multivariate statistical analysis. Metabolic signatures revealed considerable differences between pre- and post-menopausal women, and clear separations were observed between the groups in partial least-squares discriminant analysis score plots. In total, 28 metabolites were identified as potential metabolite markers for menopause, including up-regulated acylcarnitines, fatty acids, lysophosphatidylcholines, lysophosphatidylethanolamines, and down-regulated pregnanediol-3-glucuronide, dehydroepiandrosterone sulfate, p-hydroxyphenylacetic acid and dihydrolipoic acid. These differences highlight that significant alterations occur in fatty acid β-oxidation, phospholipid metabolism, hormone metabolism and amino acid metabolism in post-menopausal women. In conclusion, our plasma metabolomics study provides novel understanding of the metabolic profiles related to menopause, and will be useful for investigating menopause-related diseases and assessing metabolomic confounding factors. PMID: 26580805 [PubMed - as supplied by publisher]

Maternal dietary imbalance between omega-6 and omega-3 polyunsaturated fatty acids impairs neocortical development via epoxy metabolites. Stem Cells. 2015 Nov 18; Authors: Sakayori N, Kikkawa T, Tokuda H, Kiryu E, Yoshizaki K, Kawashima H, Yamada T, Arai H, Kang JX, Katagiri H, Shibata H, Innis SM, Arita M, Osumi N Abstract Omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) are essential nutrients. Although several studies have suggested that a balanced dietary n-6:n-3 ratio is essential for brain development, the underlying cellular and molecular mechanism is poorly understood. Here, we found that feeding pregnant mice an n-6 excess/n-3 deficient diet, which reflects modern human diets, impairs neocortical neurogenesis in the offspring. This impaired neurodevelopment occurs through a precocious fate transition of neural stem cells from the neurogenic to gliogenic lineage. A comprehensive mediator lipidomics screen revealed key mediators, epoxy metabolites, which were confirmed functionally using a neurosphere assay. Importantly, although the offspring were raised on a well-balanced n-6:n-3 diet, they exhibited increased anxiety-related behavior in adulthood. These findings provide compelling evidence that excess maternal consumption of n-6 PUFAs combined with insufficient intake of n-3 PUFAs causes abnormal brain development that can have long-lasting effects on the offspring's mental state. This article is protected by copyright. All rights reserved. PMID: 26580686 [PubMed - as supplied by publisher]

Developments in FTICR-MS and Its Potential for Body Fluid Signatures. Int J Mol Sci. 2015;16(11):27133-27144 Authors: Nicolardi S, Bogdanov B, Deelder AM, Palmblad M, van der Burgt YE Abstract Fourier transform mass spectrometry (FTMS) is the method of choice for measurements that require ultra-high resolution. The establishment of Fourier transform ion cyclotron resonance (FTICR) MS, the availability of biomolecular ionization techniques and the introduction of the Orbitrap™ mass spectrometer have widened the number of FTMS-applications enormously. One recent example involves clinical proteomics using FTICR-MS to discover and validate protein biomarker signatures in body fluids such as serum or plasma. These biological samples are highly complex in terms of the type and number of components, their concentration range, and the structural identity of each species, and thus require extensive sample cleanup and chromatographic separation procedures. Clearly, such an elaborate and multi-step sample preparation process hampers high-throughput analysis of large clinical cohorts. A final MS read-out at ultra-high resolution enables the analysis of a more complex sample and can thus simplify upfront fractionations. To this end, FTICR-MS offers superior ultra-high resolving power with accurate and precise mass-to-charge ratio (m/z) measurement of a high number of peptides and small proteins (up to 20 kDa) at isotopic resolution over a wide mass range, and furthermore includes a wide variety of fragmentation strategies to characterize protein sequence and structure, including post-translational modifications (PTMs). In our laboratory, we have successfully applied FTICR "next-generation" peptide profiles with the purpose of cancer disease classifications. Here we will review a number of developments and innovations in FTICR-MS that have resulted in robust and routine procedures aiming for ultra-high resolution signatures of clinical samples, exemplified with state-of-the-art examples for serum and saliva. PMID: 26580595 [PubMed - as supplied by publisher]

Globally Optimized Targeted Mass Spectrometry (GOT-MS): Reliable Metabolomics Analysis with Broad Coverage. Anal Chem. 2015 Nov 18; Authors: Gu H, Zhang P, Zhu J, Raftery D Abstract Targeted detection is one of the most important methods in mass spectrometry (MS)-based metabolomics; however, its major limitation is the reduced metabolome coverage that results from the limited set of targeted metabolites typically used in the analysis. In this study we describe a new approach, Globally Optimized Targeted (GOT)-MS, that combines many of the advantages of targeted detection and global profiling in metabolomics analysis, including the capability to detect unknowns, broad metabolite coverage, and excellent quantitation. The key step in GOT-MS is a global search of precursor and product ions using a single liquid chromatography triple quadrupole (LC-QQQ) mass spectrometer. Here, focused on measuring serum metabolites, we obtained 595 precursor ions and 1,890 multiple reaction monitoring (MRM) transitions, under positive and negative ionization modes in the mass range of 60-600 Da. For many of the MRMs/metabolites under investigation, the analytical performance of GOT-MS is better than or at least comparable to that obtained by global profiling using a quadrupole-time of flight (Q-TOF) instrument of similar vintage. Using a study of serum metabolites in colorectal cancer (CRC) as a representative example, GOT-MS significantly outperformed a large targeted MS assay containing ~160 biologically important metabolites, and provided a complementary approach to traditional global profiling using Q-TOF-MS. GOT-MS thus expands and optimizes the detection capabilities for QQQ-MS through a novel approach, and should have the potential to significantly advance both basic and clinical metabolic research. PMID: 26579731 [PubMed - as supplied by publisher]

Effects of antibiotic antitumor drugs on nucleotide levels in cultured tumor cells: an exploratory method to distinguish the mechanisms of antitumor drug action based on targeted metabolomics. Acta Pharm Sin B. 2015 May;5(3):223-230 Authors: Wang F, Liu X, Liu C, Liu Z, Sun L Abstract Nucleotide pools in mammalian cells change due to the influence of antitumor drugs, which may help in evaluating the drug effect and understanding the mechanism of drug action. In this study, an ion-pair RP-HPLC method was used for a simple, sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs (daunorubicin, epirubicin and dactinomycin D). Through the use of this targeted metabolomics approach to find potential biomarkers, UTP and ATP were verified to be the most appropriate biomarkers. Moreover, a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action. This model can be further validated by evaluating drugs with different mechanisms of action. This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs. PMID: 26579450 [PubMed - as supplied by publisher]

An in silico MS/MS library for automatic annotation of novel FAHFA lipids. J Cheminform. 2015;7:53 Authors: Ma Y, Kind T, Vaniya A, Gennity I, Fahrmann JF, Fiehn O Abstract BACKGROUND: A new lipid class named 'fatty acid esters of hydroxyl fatty acids' (FAHFA) was recently discovered in mammalian adipose tissue and in blood plasma and some FAHFAs were found to be associated with type 2 diabetes. To facilitate the automatic annotation of FAHFAs in biological specimens, a tandem mass spectra (MS/MS) library is needed. Due to the limitation of the commercial available standard compounds, we proposed building an in silico MS/MS library to extend the coverage of molecules. RESULTS: We developed a computer-generated library with 3267 tandem mass spectra (MS/MS) for 1089 FAHFA species. FAHFA spectra were generated based on authentic standards with negative mode electrospray ionization and 10, 20, and 40 V collision induced dissociation at 4 spectra/s as used in in ultra-high performance liquid chromatography-QTOF mass spectrometry studies. However, positional information of the hydroxyl group is only obtained either at lower QTOF spectra acquisition rates of 1 spectrum/s or at the MS(3) level in ion trap instruments. Therefore, an additional set of 4290 fragment-rich MS/MS spectra was created to enable distinguishing positional FAHFA isomers. The library was generated based on ion fragmentations and ion intensities of FAHFA external reference standards, developing a heuristic model for fragmentation rules and extending these rules to large swaths of computer-generated structures of FAHFAs with varying chain lengths, degrees of unsaturation and hydroxyl group positions. Subsequently, we validated the new in silico library by discovering several new FAHFA species in egg yolk, showing that this library enables high-throughput screening of FAHFA lipids in various biological matrices. CONCLUSIONS: The developed library and templates are freely available for commercial or noncommercial use at http://fiehnlab.ucdavis.edu/staff/yanma/fahfa-lipid-library. This in silico MS/MS library allows users to annotate FAHFAs from accurate mass tandem mass spectra in an easy and fast manner with NIST MS Search or PepSearch software. The developing template is provided for advanced users to modify the parameters and export customized libraries according to their instrument features. Graphical abstractExample of experimental and in silico MS/MS spectra for FAHFA lipids. PMID: 26579213 [PubMed - as supplied by publisher]

Metabolomic insights into the intricate gut microbial-host interaction in the development of obesity and type 2 diabetes. Front Microbiol. 2015;6:1151 Authors: Palau-Rodriguez M, Tulipani S, Isabel Queipo-Ortuño M, Urpi-Sarda M, Tinahones FJ, Andres-Lacueva C Abstract Gut microbiota has recently been proposed as a crucial environmental factor in the development of metabolic diseases such as obesity and type 2 diabetes, mainly due to its contribution in the modulation of several processes including host energy metabolism, gut epithelial permeability, gut peptide hormone secretion, and host inflammatory state. Since the symbiotic interaction between the gut microbiota and the host is essentially reflected in specific metabolic signatures, much expectation is placed on the application of metabolomic approaches to unveil the key mechanisms linking the gut microbiota composition and activity with disease development. The present review aims to summarize the gut microbial-host co-metabolites identified so far by targeted and untargeted metabolomic studies in humans, in association with impaired glucose homeostasis and/or obesity. An alteration of the co-metabolism of bile acids, branched fatty acids, choline, vitamins (i.e., niacin), purines, and phenolic compounds has been associated so far with the obese or diabese phenotype, in respect to healthy controls. Furthermore, anti-diabetic treatments such as metformin and sulfonylurea have been observed to modulate the gut microbiota or at least their metabolic profiles, thereby potentially affecting insulin resistance through indirect mechanisms still unknown. Despite the scarcity of the metabolomic studies currently available on the microbial-host crosstalk, the data-driven results largely confirmed findings independently obtained from in vitro and animal model studies, putting forward the mechanisms underlying the implication of a dysfunctional gut microbiota in the development of metabolic disorders. PMID: 26579078 [PubMed - as supplied by publisher]

The investigation of anti-inflammatory activity of volatile oil of Angelica sinensis by plasma metabolomics approach. Int Immunopharmacol. 2015 Nov 11; Authors: Yao W, Zhang L, Hua Y, Ji P, Li P, Li J, Zhong L, Zhao H, Wei Y Abstract Angelica sinensis (AS) is an important medicinal plant, and volatile oil is the main pharmacologically active ingredient. This study was aimed to investigate the anti-inflammatory activity of the volatile oil of A. sinensis (VOAS) and explore its potential anti-inflammatory mechanism by plasma metabolomics approach. Rat acute inflammation was induced by subcutaneous injection of carrageenan in hind paws. Paw edema, histamine (HIS) and 5-hydroxytryptamine (5-HT) were detected. Then, we analyzed plasma metabolic profiling of acute inflammation and performed pathway analysis on the metabolite markers reversed after VOAS administration and further integration of metabolic networks. The results showed that VOAS could alleviate the paw edema and decrease plasma HIS and 5-HT levels. Fourteen metabolite markers of acute inflammation were screened, and the levels were all reversed to different degrees after VOAS administration. These metabolite markers mainly related to linoleic acid metabolism, ascorbate and aldarate metabolism, arachidonic acid metabolism, glyoxylate and dicarboxylate metabolism, and glycine, serine and threonine metabolism. In metabolic networks, glycine and arachidonic acid were node molecules. It indicated that VOAS could significantly inhibit systemic inflammatory response triggered by acute local stimulation and it exerted anti-inflammatory activity mainly through regulating the disturbed metabolic networks centered on glycine and arachidonic acid. PMID: 26578286 [PubMed - as supplied by publisher]

Metabolomics reveals hippocampal metabolic fluctuations of postoperative fatigue syndrome and anti-fatigue effect of Carthamus tinctorius L extract in rat model. Biomed Chromatogr. 2015 Nov 17; Authors: Lu Y, Ning H, Jiang X, Yang R, Song D, Yuan H Abstract Postoperative fatigue syndrome (POFS) is a common clinical complication followed by almost every major abdominal surgery. There is not a full explanation to the etiology of POFS, especially its central mechanism. Carthamus tinctorius L is a classic traditional Chinese medicine (TCM) which could exert the anti-fatigue effect on POFS. However, its mechanism is still lacking. Here, ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS) based metabonomic approach was used to characterize hippocampal metabolic fluctuations of POFS in a rat model induced by partial hepatectomy (PHx), and to evaluate the anti-fatigue effect of Carthamus tinctorius L extract (CTLE). With partial least-squares discriminant analysis for classification and selection of biomarkers, fifteen hippocampal metabolites related to POFS were identified, primarily involving alanine, aspartate and glutamate metabolism, valine, leucine and isoleucine degradation, purine metabolism, phenylalanine metabolism, tryptophan metabolism, phospholipid metabolism and fatty acid metabolism. With these altered metabolic pathways as possible drug targets, we systematically analyzed the protective effect of CTLE, which showed that CTLE could provide anti-fatigue effect on POFS through partially regulating the perturbed metabolic pathways. This study indicated that UHPLC-Q-TOFMS-based metabolomics provided a powerful tool to reveal hippocampal metabolic fluctuations of POFS and study the mechanism of TCM. This article is protected by copyright. All rights reserved. PMID: 26577245 [PubMed - as supplied by publisher]

Metabolomic profiling of urinary changes in mice with monosodium glutamate-induced obesity. Anal Bioanal Chem. 2015 Nov 17; Authors: Pelantová H, Bártová S, Anýž J, Holubová M, Železná B, Maletínská L, Novák D, Lacinová Z, Šulc M, Haluzík M, Kuzma M Abstract Obesity with related complications represents a widespread health problem. The etiopathogenesis of obesity is often studied using numerous rodent models. The mouse model of monosodium glutamate (MSG)-induced obesity was exploited as a model of obesity combined with insulin resistance. The aim of this work was to characterize the metabolic status of MSG mice by NMR-based metabolomics in combination with relevant biochemical and hormonal parameters. NMR analysis of urine at 2, 6, and 9 months revealed altered metabolism of nicotinamide and polyamines, attenuated excretion of major urinary proteins, increased levels of phenylacetylglycine and allantoin, and decreased concentrations of methylamine in urine of MSG-treated mice. Altered levels of creatine, citrate, succinate, and acetate were observed at 2 months of age and approached the values of control mice with aging. The development of obesity and insulin resistance in 6-month-old MSG mice was also accompanied by decreased mRNA expressions of adiponectin, lipogenetic and lipolytic enzymes and peroxisome proliferator-activated receptor-gamma in fat while mRNA expressions of lipogenetic enzymes in the liver were enhanced. At the age of 9 months, biochemical parameters of MSG mice were normalized to the values of the controls. This fact pointed to a limited predictive value of biochemical data up to age of 6 months as NMR metabolomics confirmed altered urine metabolic composition even at 9 months. PMID: 26577083 [PubMed - as supplied by publisher]

Quantitative resistance against Bemisia tabaci in Solanum pennellii: Genetics and metabolomics. J Integr Plant Biol. 2015 Nov 18; Authors: van den Oever-van den Elsen F, Lucatti AF, van Heusden S, Broekgaarden C, Mumm R, Dicke M, Vosman B Abstract The whitefly Bemisia tabaci is a serious threat in tomato cultivation worldwide as all varieties grown today are highly susceptible to this devastating herbivorous insect. Many accessions of the tomato wild relative Solanum pennellii show a high resistance towards B. tabaci. A mapping approach was employed to elucidate the genetic background of whitefly-resistance related traits and associated biochemical traits in this species. Minor quantitative trait loci (QTLs) for whitefly adult survival (AS) and oviposition rate (OR) were identified and some were confirmed in an F2 BC1 population, where they showed increased percentages of explained variance (more than 30%). Bulked segregant analyses on pools of whitefly-resistant and -susceptible F2 plants enabled the identification of metabolites that correlate either with resistance or susceptibility. Genetic mapping of these metabolites showed that a large number of them co-localize with whitefly-resistance QTLs. Some of these whitefly-resistance QTLs are hotspots for metabolite QTLs. Although a large number of metabolite QTLs correlated to whitefly resistance or susceptibility, most of them are yet unknown compounds and further studies are needed to identify the metabolic pathways and genes involved. The results indicate a direct genetic correlation between biochemical-based resistance characteristics and reduced whitefly incidence in S. pennellii. PMID: 26576823 [PubMed - as supplied by publisher]

Related Articles Defective autophagy gets to the brain. Oncotarget. 2015 Nov 13; Authors: Galluzzi L, Kroemer G PMID: 26575951 [PubMed - as supplied by publisher]

Related Articles Nuclear magnetic resonance (NMR) spectroscopy: Metabolic profiling of medicinal plants and their products. Crit Rev Anal Chem. 2015 Nov 17;:0 Authors: Kumar D Abstract NMR spectroscopy has multidisciplinary applications and excellent impact in metabolomics. Analytical capacity of NMR spectroscopy provides information regarding easy qualitative and quantitative assessment of both endogenous and exogenous metabolites present in biological samples. Complexity of a particular metabolite and its contribution in a biological system is critically important for understanding the functional state that governs the organism's phenotypes. This review covers historical aspects of developments in NMR field, its applications in chemical profiling, metabolomics, and quality control of plants and their derived medicine, food etc. The bottlenecks of NMR in metabolic profiling have also been discussed by keeping in view the future scope and more technological interventions. PMID: 26575437 [PubMed - as supplied by publisher]

Related Articles Cyclic di-GMP regulates multiple cellular functions in the symbiotic α-proteobacterium Sinorhizobium meliloti. J Bacteriol. 2015 Nov 16; Authors: Schäper S, Krol E, Skotnicka D, Kaever V, Hilker R, Søgaard-Andersen L, Becker A Abstract Sinorhizobium meliloti undergoes major lifestyle changes between planktonic states, biofilm formation and symbiosis with leguminous plant hosts. In many bacteria, the second messenger 3' ,5' -cyclic diguanylic acid (c-di-GMP, cdG) promotes a sessile lifestyle by regulating a plethora of processes involved in biofilm formation, including motility and biosynthesis of exopolysaccharides (EPS). Here, we systematically investigated the role of cdG in S. meliloti Rm2011 encoding 22 proteins putatively associated with cdG synthesis, degradation or binding. Single mutations in 21 of these genes did not cause evident changes in biofilm formation, motility or EPS biosynthesis. In contrast, manipulation of cdG levels by overproducing endogenous or heterologous diguanylate cyclases (DGCs) or phosphodiesterases (PDEs) affected these processes and accumulation of N-Acyl-homoserine lactones in the culture supernatant. Specifically, individual overexpression of the S. meliloti genes pleD, SMb20523, SMb20447, SMc01464 and SMc03178 encoding putative DGCs, and of SMb21517 encoding a single domain PDE protein had an impact and resulted in increased levels of cdG. Compared to wild type, a S. meliloti cdG(0) strain that did not produce detectable levels of cdG was more sensitive to acid stress. However, it was symbiotically potent, unaffected in motility and only slightly reduced in biofilm formation. The SMc01790-SMc01796 locus, homologous to the Agrobacterium tumefaciens uppABCDEF cluster governing biosynthesis of a unipolarly localized polysaccharide, was found to be required for cdG-stimulated biofilm formation, while the single domain PilZ protein McrA was identified as a cdG receptor protein involved in regulation of motility. IMPORTANCE: We present the first systematic genome-wide investigation of the role of 3' ,5' -cyclic diguanylic acid (c-di-GMP, cdG) in regulation of motility, biosynthesis of exopolysaccharides, biofilm formation, quorum sensing and symbiosis in a symbiotic alpha-rhizobial species. Phenotypes of a S. meliloti cdG(0) strain unable to produce cdG demonstrated that this second messenger is not essential for root nodule symbiosis but may contribute to acid tolerance. Our data further suggest that enhanced levels of cdG promote sessility of S. meliloti and uncovered a single domain PilZ protein as regulator of motility. PMID: 26574513 [PubMed - as supplied by publisher]

Related Articles Mechanotransduction in primary human osteoarthritic chondrocytes is mediated by metabolism of energy, lipids, and amino acids. J Biomech. 2015 Oct 31; Authors: Zignego DL, Hilmer JK, June RK Abstract Chondrocytes are the sole cell type found in articular cartilage and are repeatedly subjected to mechanical loading in vivo. We hypothesized that physiological dynamic compression results in changes in energy metabolism to produce proteins for maintenance of the pericellular and extracellular matrices. The objective of this study was to develop an in-depth understanding for the short term (<30min) chondrocyte response to sub-injurious, physiological compression by analyzing metabolomic profiles for human chondrocytes harvested from femoral heads of osteoarthritic donors. Cell-seeded agarose constructs were randomly assigned to experimental groups, and dynamic compression was applied for 0, 15, or 30min. Following dynamic compression, metabolites were extracted and detected by HPLC-MS. Untargeted analyzes examined changes in global metabolomics profiles and targeted analysis examined the expression of specific metabolites related to central energy metabolism. We identified hundreds of metabolites that were regulated by applied compression, and we report the detection of 16 molecules not found in existing metabolite databases. We observed patient-specific mechanotransduction with aging dependence. Targeted studies found a transient increase in the ratio of NADP+ to NADPH and an initial decrease in the ratio of GDP to GTP, suggesting a flux of energy into the TCA cycle. By characterizing metabolomics profiles of primary chondrocytes in response to applied dynamic compression, this study provides insight into how OA chondrocytes respond to mechanical load. These results are consistent with increases in glycolytic energy utilization by mechanically induced signaling, and add substantial new data to a complex picture of how chondrocytes transduce mechanical loads. PMID: 26573901 [PubMed - as supplied by publisher]

Related Articles The neuroimmune guidance cue netrin-1 controls resolution programs and promotes liver regeneration. Hepatology. 2015 Nov 17; Authors: Schlegel M, Köhler D, Körner A, Granja T, Straub A, Giera M, Mirakaj V Abstract Hepatic ischemia/reperfusion (I/R) is a major adverse reaction to liver transplantation, hemorrhagic shock, or resection. Recently, the anti-inflammatory properties of the axonal guidance cue netrin-1 were reported. Here, we demonstrate that netrin-1 also impacts the resolution of inflammation and promotes hepatic repair and regeneration during liver I/R injury. In initial studies, we investigated the induction of netrin-1 and its receptors in murine liver tissues after I/R injury. Hepatic I/R injury was performed in mice with a partial genetic netrin-1 deficiency (Ntn1(+/-) ) or wild-type C57BL/6 treated with exogenous netrin-1 to examine the endogenous and therapeutically administered impact of netrin-1. These investigations were corroborated by studies determining the characteristics of intravascular leukocyte flow, clearance of apoptotic neutrophils (PMN), production of specialized pro-resolving lipid mediators (SPM), generation of specific growth factors contributing to the resolution of inflammation and liver repair. Hepatic I/R was associated with a significant reduction of netrin-1 transcript and protein in murine liver tissue. Subsequent studies in netrin-1-deficient mice revealed lower efficacies in reducing PMN infiltration, pro-inflammatory cytokine levels and hepatic-specific injury enzymes. Conversely, mice treated with exogenous netrin-1 exhibited increased liver protection and repair, reducing neutrophil influx into the injury site, decreasing pro-inflammatory mediators, increasing efferocytosis of apoptotic PMN, stimulating local endogenous biosynthesis of SPM and the generation of specific growth factors. Lastly, genetic studies implicated the A2B adenosine receptor in netrin-1-mediated protection during hepatic I/R injury. CONCLUSION: The present study indicates a previously unrecognized role for netrin-1 in liver protection and its contribution to tissue homeostasis and regeneration. This article is protected by copyright. All rights reserved. PMID: 26573873 [PubMed - as supplied by publisher]

Related Articles Litomosoides sigmodontis: A jird urine metabolome study. Bioorg Med Chem Lett. 2015 Oct 23; Authors: Globisch D, Specht S, Pfarr KM, Eubanks LM, Hoerauf A, Janda KD Abstract The neglected tropical disease onchocerciasis affects more than 35 million people worldwide with over 95% in Africa. Disease infection initiates from the filarial parasitic nematode Onchocerca volvulus, which is transmitted by the blackfly vector Simulium sp. carrying infectious L3 larvae. New treatments and diagnostics are required to eradicate this parasitic disease. Herein, we describe that a previously discovered biomarker for onchocerciasis, N-acetyltyramine-O-glucuronide (NATOG) is also present in urine samples of jirds infected with the onchocerciasis model nematode Litomosoides sigmodontis. Increased NATOG values paralleled a progressing infection and demonstrated that quantification of NATOG in this rodent model can be utilized to track its infectivity. Moreover, our findings suggest how NATOG monitoring may be used for evaluating potential drug candidates. PMID: 26573416 [PubMed - as supplied by publisher]

Related Articles Genomic mutational analysis of the impact of the classical strain improvement program on β-lactam producing Penicillium chrysogenum. BMC Genomics. 2015;16(1):937 Authors: Salo OV, Ries M, Medema MH, Lankhorst PP, Vreeken RJ, Bovenberg RA, Driessen AJ Abstract BACKGROUND: Penicillium chrysogenum is a filamentous fungus that is employed as an industrial producer of β-lactams. The high β-lactam titers of current strains is the result of a classical strain improvement program (CSI) starting with a wild-type like strain more than six decades ago. This involved extensive mutagenesis and strain selection for improved β-lactam titers and growth characteristics. However, the impact of the CSI on the secondary metabolism in general remains unknown. RESULTS: To examine the impact of CSI on secondary metabolism, a comparative genomic analysis of β-lactam producing strains was carried out by genome sequencing of three P. chrysogenum strains that are part of a lineage of the CSI, i.e., strains NRRL1951, Wisconsin 54-1255, DS17690, and the derived penicillin biosynthesis cluster free strain DS68530. CSI has resulted in a wide spread of mutations, that statistically did not result in an over- or underrepresentation of specific gene classes. However, in this set of mutations, 8 out of 31 secondary metabolite genes (20 polyketide synthases and 11 non-ribosomal peptide synthetases) were targeted with a corresponding and progressive loss in the production of a range of secondary metabolites unrelated to β-lactam production. Additionally, key Velvet complex proteins (LeaA and VelA) involved in global regulation of secondary metabolism have been repeatedly targeted for mutagenesis during CSI. Using comparative metabolic profiling, the polyketide synthetase gene cluster was identified that is responsible for sorbicillinoid biosynthesis, a group of yellow-colored metabolites that are abundantly produced by early production strains of P. chrysogenum. CONCLUSIONS: The classical industrial strain improvement of P. chrysogenum has had a broad mutagenic impact on metabolism and has resulted in silencing of specific secondary metabolite genes with the concomitant diversion of metabolism towards the production of β-lactams. PMID: 26572918 [PubMed - as supplied by publisher]

Related Articles From sample treatment to biomarker discovery: A tutorial for untargeted metabolomics based on GC-(EI)-Q-MS. Anal Chim Acta. 2015 Nov 5;900:21-35 Authors: Mastrangelo A, Ferrarini A, Rey-Stolle F, García A, Barbas C Abstract This tutorial provides a comprehensive description of the GC-MS-based untargeted metabolomics workflow including: ethical approval requirement, sample collection and storage, equipment maintenance and setup, sample treatment, monitoring of analytical variability, data pre-processing including deconvolution by free software such as AMDIS, data processing, statistical analysis and validation, detection of outliers and biological interpretation of the results. For each stage tricks will be suggested, pitfalls will be highlighted and advice will be provided on how to get the best from this methodology and technique. In addition, a step-by-step procedure and an example of our in-house library have been included in the supplementary material to lead the user through the concepts described herein. As a case study, an interesting example from one of our experiments at CEMBIO Research Centre is described, presenting an example of the use of this ready-to use protocol for identification of a metabolite that was not previously included in Fiehn commercial target library. PMID: 26572836 [PubMed - in process]

Related Articles Novel Analytical Workflow for Comprehensive Non-targeted Phytochemical Metabolic Profiling. Chimia (Aarau). 2015;69(5):294-5 Authors: Hettich T, Schlotterbeck G Abstract The understanding and interpretation of pharmacological properties on a molecular level is of great importance for many different fields of research. Our study provides a novel model work-flow for comprehensive metabolic profiling by structural identification of relevant metabolites not limited to phytochemistry applications. High resolution liquid chromatography mass spectrometry LC-MS/MS data can be directly correlated with pharmacological test results on a molecular level. Thus the understanding and interpretation of pharmacological properties is supported by structural and chemical information. PMID: 26507349 [PubMed - indexed for MEDLINE]