Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma.

Wed, 27/02/2019 - 12:33
Related Articles Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma. Endocrinology. 2018 08 01;159(8):2836-2849 Authors: Chortis V, Taylor AE, Doig CL, Walsh MD, Meimaridou E, Jenkinson C, Rodriguez-Blanco G, Ronchi CL, Jafri A, Metherell LA, Hebenstreit D, Dunn WB, Arlt W, Foster PA Abstract Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from oxidative stress. Inactivating human NNT mutations result in congenital adrenal insufficiency. We hypothesized that NNT silencing in ACC cells will induce toxic levels of oxidative stress. To explore this, we transiently knocked down NNT in NCI-H295R ACC cells. As predicted, this manipulation increased intracellular levels of oxidative stress; this resulted in a pronounced suppression of cell proliferation and higher apoptotic rates, as well as sensitization of cells to chemically induced oxidative stress. Steroidogenesis was paradoxically stimulated by NNT loss, as demonstrated by mass spectrometry-based steroid profiling. Next, we generated a stable NNT knockdown model in the same cell line to investigate the longer lasting effects of NNT silencing. After long-term culture, cells adapted metabolically to chronic NNT knockdown, restoring their redox balance and resilience to oxidative stress, although their proliferation remained suppressed. This was associated with higher rates of oxygen consumption. The molecular pathways underpinning these responses were explored in detail by RNA sequencing and nontargeted metabolome analysis, revealing major alterations in nucleotide synthesis, protein folding, and polyamine metabolism. This study provides preclinical evidence of the therapeutic merit of antioxidant targeting in ACC as well as illuminating the long-term adaptive response of cells to oxidative stress. PMID: 29850793 [PubMed - indexed for MEDLINE]

Assessing Flux Distribution Associated with Metabolic Specialization of Glandular Trichomes.

Wed, 27/02/2019 - 12:33
Related Articles Assessing Flux Distribution Associated with Metabolic Specialization of Glandular Trichomes. Trends Plant Sci. 2018 07;23(7):638-647 Authors: Zager JJ, Lange BM Abstract Many aromatic plants accumulate mixtures of secondary (or specialized) metabolites in anatomical structures called glandular trichomes (GTs). Different GT types may also synthesize different mixtures of secreted metabolites, and this contributes to the enormous chemical diversity reported to occur across species. Over the past two decades, significant progress has been made in characterizing the genes and enzymes that are responsible for the unique metabolic capabilities of GTs in different lineages of flowering plants. Less is known about the processes that regulate flux distribution through precursor pathways toward metabolic end-products. We discuss here the results from a meta-analysis of genome-scale models that were developed to capture the unique metabolic capabilities of different GT types. PMID: 29735428 [PubMed - indexed for MEDLINE]

Effect of Maternal Smoking on Plasma and Urinary Measures of Vitamin E Isoforms in the First Month after Extreme Preterm Birth.

Wed, 27/02/2019 - 12:33
Related Articles Effect of Maternal Smoking on Plasma and Urinary Measures of Vitamin E Isoforms in the First Month after Extreme Preterm Birth. J Pediatr. 2018 06;197:280-285.e3 Authors: Stone C, Qiu Y, Kurland IJ, Slaughter JC, Moore P, Cook-Mills J, Hartert T, Aschner JL Abstract We examined the effect of maternal smoking on plasma and urinary levels of vitamin E isoforms in preterm infants. Maternal smoking during pregnancy decreased infant plasma alpha- and gamma-tocopherol concentrations at 1 week and 4 weeks, with 45% of infants of smokers deficient in alpha-tocopherol at 1 month after birth. PMID: 29398053 [PubMed - indexed for MEDLINE]

Rice SUB1A constrains remodelling of the transcriptome and metabolome during submergence to facilitate post-submergence recovery.

Wed, 27/02/2019 - 12:33
Related Articles Rice SUB1A constrains remodelling of the transcriptome and metabolome during submergence to facilitate post-submergence recovery. Plant Cell Environ. 2018 04;41(4):721-736 Authors: Locke AM, Barding GA, Sathnur S, Larive CK, Bailey-Serres J Abstract The rice (Oryza sativa L.) ethylene-responsive transcription factor gene SUB1A-1 confers tolerance to prolonged, complete submergence by limiting underwater elongation growth. Upon desubmergence, SUB1A-1 genotypes rapidly recover photosynthetic function and recommence development towards flowering. The underpinnings of the transition from stress amelioration to the return to homeostasis are not well known. Here, transcriptomic and metabolomic analyses were conducted to identify mechanisms by which SUB1A improves physiological function over the 24 hr following a sublethal submergence event. Evaluation of near-isogenic genotypes after submergence and over a day of reaeration demonstrated that SUB1A transiently constrains the remodelling of cellular activities associated with growth. SUB1A influenced the abundance of ca. 1,400 transcripts and had a continued impact on metabolite content, particularly free amino acids, glucose, and sucrose, throughout the recovery period. SUB1A promoted recovery of metabolic homeostasis but had limited influence on mRNAs associated with growth processes and photosynthesis. The involvement of low energy sensing during submergence and recovery was supported by dynamics in trehalose-6-phosphate and mRNAs encoding key enzymes and signalling proteins, which were modulated by SUB1A. This study provides new evidence of convergent signalling pathways critical to the rapidly reversible management of carbon and nitrogen metabolism in submergence resilient rice. PMID: 29094353 [PubMed - indexed for MEDLINE]

Dietary copper-fructose interactions alter gut microbial activity in male rats.

Wed, 27/02/2019 - 12:33
Related Articles Dietary copper-fructose interactions alter gut microbial activity in male rats. Am J Physiol Gastrointest Liver Physiol. 2018 01 01;314(1):G119-G130 Authors: Song M, Li X, Zhang X, Shi H, Vos MB, Wei X, Wang Y, Gao H, Rouchka EC, Yin X, Zhou Z, Prough RA, Cave MC, McClain CJ Abstract Dietary copper-fructose interactions contribute to the development of nonalcoholic fatty liver disease (NAFLD). Gut microbiota play critical roles in the pathogenesis of NAFLD. The aim of this study was to determine the effect of different dietary doses of copper and their interactions with high fructose on gut microbiome. Male weanling Sprague-Dawley rats were fed diets with adequate copper (6 ppm CuA), marginal copper (1.5 ppm CuM) (low copper), or supplemented copper (20 ppm CuS) (high copper) for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was given ad libitum. Copper status, liver enzymes, gut barrier function, and gut microbiome were evaluated. Both low- and high-copper diets led to liver injury in high-fructose-fed rats, and this was associated with gut barrier dysfunction, as shown by the markedly decreased tight junction proteins and increased gut permeability. 16S rDNA sequencing analysis revealed distinct alterations of the gut microbiome associated with dietary low- and high-copper/high-fructose feeding. The common features of the alterations of the gut microbiome were the increased abundance of Firmicutes and the depletion of Akkermansia. However, they differed mainly within the phylum Firmicutes. Our data demonstrated that a complex interplay among host, microbes, and dietary copper-fructose interaction regulates gut microbial metabolic activity, which may contribute to the development of liver injury and hepatic steatosis. The distinct alterations of gut microbial activity, which were associated with the different dietary doses of copper and fructose, imply that separate mechanism(s) may be involved. NEW & NOTEWORTHY First, dietary low- and high-copper/high-fructose-induced liver injury are associated with distinct alterations of gut microbiome. Second, dietary copper level plays a critical role in maintaining the gut barrier integrity, likely by acting on the intestinal tight junction proteins and the protective commensal bacteria Akkermansia. Third, the alterations of gut microbiome induced by dietary low and high copper with or without fructose differ mainly within the phylum Firmicutes. PMID: 29025734 [PubMed - indexed for MEDLINE]

metabolomics; +42 new citations

Tue, 26/02/2019 - 21:11
42 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 2019/02/26PubMed comprises more than millions of 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.

Global Metabolic Analyses of Acinetobacter baumannii.

Mon, 25/02/2019 - 14:56
Related Articles Global Metabolic Analyses of Acinetobacter baumannii. Methods Mol Biol. 2019;1946:321-328 Authors: Mahamad Maifiah MH, Velkov T, Creek DJ, Li J Abstract Acinetobacter baumannii is rapidly emerging as a multidrug-resistant pathogen responsible for nosocomial infections including pneumonia, bacteremia, wound infections, urinary tract infections, and meningitis. Metabolomics provides a powerful tool to gain a system-wide snapshot of cellular biochemical networks under defined conditions and has been increasingly applied to bacterial physiology and drug discovery. Here we describe an optimized sample preparation method for untargeted metabolomics studies in A. baumannii. Our method provides a significant recovery of intracellular metabolites to demonstrate substantial differences in global metabolic profiles among A. baumannii strains. PMID: 30798566 [PubMed - in process]

Dissection of the network of indolic defence compounds in Arabidopsis thaliana by multiple mutant analysis.

Mon, 25/02/2019 - 14:56
Related Articles Dissection of the network of indolic defence compounds in Arabidopsis thaliana by multiple mutant analysis. Phytochemistry. 2019 Feb 21;161:11-20 Authors: Müller TM, Böttcher C, Glawischnig E Abstract Characteristic for cruciferous plants is the synthesis of a complex array of defence-related indolic compounds. In Arabidopsis, these include indol-3-ylmethyl glucosinolates (IMGs), as well as stress-inducible indole-3-carbaldehyde (ICHO)/indole-3-carboxylic acid (ICOOH) derivatives and camalexin. Key enzymes in the biosynthesis of the inducible metabolites are the cytochrome P450 enzymes CYP71A12, CYP71A13 and CYP71B6 and Arabidopsis Aldehyde Oxidase 1 (AAO1). Multiple mutants in the corresponding genes were generated and their metabolic phenotypes were comprehensively analysed in untreated, UV exposed and silver nitrate-treated leaves. Most strikingly, ICOOH and ICHO derivatives synthesized in response to UV exposure were not metabolically related. While ICHO concentrations correlated with IMGs, ICOOH derivatives were anti-correlated with IMGs and partially dependent on CYP71B6. The AAO1 genotype was shown to not only be important for ICHO metabolism but also for the accumulation of 4-pyridoxic acid, suggesting a dual role of AAO1 in vitamin B6 metabolism and IMG degradation in Arabidopsis. PMID: 30798200 [PubMed - as supplied by publisher]

Cultivar differentiation of Citri Reticulatae Pericarpium by a combination of hierarchical three-step filtering metabolomics analysis, DNA barcoding and electronic nose.

Mon, 25/02/2019 - 14:56
Related Articles Cultivar differentiation of Citri Reticulatae Pericarpium by a combination of hierarchical three-step filtering metabolomics analysis, DNA barcoding and electronic nose. Anal Chim Acta. 2019 May 16;1056:62-69 Authors: Li SZ, Zeng SL, Wu Y, Zheng GD, Chu C, Yin Q, Chen BZ, Li P, Lu X, Liu EH Abstract The traditional Chinese medicine Citri Reticulatae Pericarpium (CRP) was mainly originated from the dried pericarp of Citrus reticulata 'Chachi' (Crc), Citrus reticulata 'Dahongpao' (Crd), Citrus reticulata 'Unshiu' (Cru) and Citrus reticulata 'Tangerina' (Crt) in China. Since these four cultivars have great similarities in morphology, reliable methods to differentiate CRP cultivars have rarely been reported. To discriminate the differences of these CRP cultivars, herein an efficient and reliable method by combining metabolomics, DNA barcoding and electronic nose was first established. The hierarchical three-step filtering metabolomics analysis based on liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) indicated that 9 species-specific chemical markers including 6 flavanone glycosides and 3 polymethoxyflavones could be considered as marker metabolites for discrimination of the geoherb Crc from other cultivars. A total of 19 single nucleotide polymorphism (SNP) sites were found in nuclear internal transcribed spacer 2 (ITS2) of CRP, and three stable SNP sites (33, 128 and 174) in the ITS2 region can distinguish the four CRP cultivars. The electronic nose coupled with chemometrics could also be used to effectively distinguish Crc from other CRP cultivars. Therefore, our results indicated that the integrated method will be an effective strategy for discrimination of similar herbal medicines. PMID: 30797461 [PubMed - in process]

Endorsing and extending the repertory of nutraceutical and antioxidant sources in mangoes during postharvest shelf life.

Mon, 25/02/2019 - 14:56
Related Articles Endorsing and extending the repertory of nutraceutical and antioxidant sources in mangoes during postharvest shelf life. Food Chem. 2019 Jul 01;285:119-129 Authors: Monribot-Villanueva JL, Elizalde-Contreras JM, Aluja M, Segura-Cabrera A, Birke A, Guerrero-Analco JA, Ruiz-May E Abstract Mango byproducts, such as peels, contain high levels of antioxidants and fiber and represent important sources of nutraceuticals and pharmacological products. Fruit are collected at the mature green stage then stored and ripened, undergoing several structural and molecular changes over the course of this process. However, very little is known regarding the content and nature of antioxidant compounds in peels of elite and local cultivars during postharvest shelf life (PSL). We screened the phenolic compound content of six cultivars during PSL, including elite (Kent, Tommy, and Ataulfo) and local (Manila, Manililla, and Criollo) mangoes, using a targeted metabolomics approach. We determined that Ataulfo mangoes exhibited the highest content of phenolic compounds during PSL. Untargeted metabolomics and comparative proteomics in Ataulfo and Manililla showed these cultivars to be significant sources of phenolic and lipidic compounds, with the latter cultivar also representing an interesting candidate as a new source for nutraceutical products. PMID: 30797326 [PubMed - in process]

Plasma metabolites predict both insulin resistance and incident type 2 diabetes: a metabolomics approach within the Prevención con Dieta Mediterránea (PREDIMED) study.

Sun, 24/02/2019 - 14:35
Related Articles Plasma metabolites predict both insulin resistance and incident type 2 diabetes: a metabolomics approach within the Prevención con Dieta Mediterránea (PREDIMED) study. Am J Clin Nutr. 2019 Feb 23;: Authors: Papandreou C, Bulló M, Ruiz-Canela M, Dennis C, Deik A, Wang D, Guasch-Ferré M, Yu E, Razquin C, Corella D, Estruch R, Ros E, Fitó M, Fiol M, Liang L, Hernández-Alonso P, Clish CB, Martínez-González MA, Hu FB, Salas-Salvadó J Abstract BACKGROUND: Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D). OBJECTIVES: The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D. METHODS: We used a case-cohort study nested within the Prevención con Dieta Mediterránea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography-tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR-related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models. RESULTS: We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors. CONCLUSIONS: The multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D. PMID: 30796776 [PubMed - as supplied by publisher]

GC-QTOFMS with a low-energy electron ionization source for advancing isotopologue analysis in 13C-based metabolic flux analysis.

Sun, 24/02/2019 - 14:35
Related Articles GC-QTOFMS with a low-energy electron ionization source for advancing isotopologue analysis in 13C-based metabolic flux analysis. Anal Bioanal Chem. 2019 Feb 22;: Authors: Mairinger T, Sanderson J, Hann S Abstract For the study of different levels of (intra)cellular regulation and condition-dependent insight into metabolic activities, fluxomics experiments based on stable isotope tracer experiments using 13C have become a well-established approach. The experimentally obtained non-naturally distributed 13C labeling patterns of metabolite pools can be measured by mass spectrometric detection with front-end separation and can be consequently incorporated into biochemical network models. Here, despite a tedious derivatization step, gas chromatographic separation of polar metabolites is favorable because of the wide coverage range and high isomer separation efficiency. However, the typically employed electron ionization energy of 70 eV leads to significant fragmentation and consequently only low-abundant ions with an intact carbon backbone. Since these ions are considered a prerequisite for the analysis of the non-naturally distributed labeling patterns and further integration into modeling strategies, a softer ionization technique is needed. In the present work, a novel low energy electron ionization source is optimized for the analysis of primary metabolites and compared with a chemical ionization approach in terms of trueness, precision, and sensitivity. PMID: 30796486 [PubMed - as supplied by publisher]

Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery.

Sun, 24/02/2019 - 14:35
Related Articles Urinary metabolic variation analysis during pregnancy and application in Gestational Diabetes Mellitus and spontaneous abortion biomarker discovery. Sci Rep. 2019 Feb 22;9(1):2605 Authors: Liu X, Wang X, Sun H, Guo Z, Liu X, Yuan T, Fu Y, Tang X, Li J, Sun W, Zhao W Abstract Pregnancy is associated with the onset of many adaptation processes that are likely to change over the course of gestation. Understanding normal metabolites' variation with pregnancy progression is crucial for gaining insights of the key nutrients for normal fetal growth, and for comparative research of pregnancy-related complications. This work presents liquid chromatography-mass spectrum-based urine metabolomics study of 50 health pregnant women at three time points during pregnancy. The influence of maternal physiological factors, including age, BMI, parity and gravity to urine metabolome was explored. Additionally, urine metabolomics was applied for early prediction of two pregnancy complications, gestational diabetes mellitus and spontaneous abortion. Our results suggested that during normal pregnancy progression, pathways of steroid hormone biosynthesis and tyrosine metabolism were significantly regulated. BMI is a factor that should be considered during cross-section analysis. Application analysis discovered potential biomarkers for GDM in the first trimester with AUC of 0.89, and potential biomarkers for SA in the first trimester with AUC of 0.90. In conclusion, our study indicated that urine metabolome could reflect variations during pregnancy progression, and has potential value for pregnancy complications early prediction. The clinical trial number for this study is NCT03246295. PMID: 30796299 [PubMed - in process]

Application of metabolomics and molecular networking in investigating the chemical profile and antitrypanosomal activity of British bluebells (Hyacinthoides non-scripta).

Sun, 24/02/2019 - 14:35
Related Articles Application of metabolomics and molecular networking in investigating the chemical profile and antitrypanosomal activity of British bluebells (Hyacinthoides non-scripta). Sci Rep. 2019 Feb 22;9(1):2547 Authors: Raheem DJ, Tawfike AF, Abdelmohsen UR, Edrada-Ebel R, Fitzsimmons-Thoss V Abstract Bulb, leaf, scape and flower samples of British bluebells (Hyacinthoides non-scripta) were collected regularly for one growth period. Methanolic extracts of freeze-dried and ground samples showed antitrypanosomal activity, giving more than 50% inhibition, for 20 out of 41 samples. High-resolution mass spectrometry was used in the dereplication of the methanolic extracts of the different plant parts. The results revealed differences in the chemical profile with bulb samples being distinctly different from all aerial parts. High molecular weight metabolites were more abundant in the flowers, shoots and leaves compared to smaller molecular weight ones in the bulbs. The anti-trypanosomal activity of the extracts was linked to the accumulation of high molecular weight compounds, which were matched with saponin glycosides, while triterpenoids and steroids occurred in the inactive extracts. Dereplication studies were employed to identify the significant metabolites via chemotaxonomic filtration and considering their previously reported bioactivities. Molecular networking was implemented to look for similarities in fragmentation patterns between the isolated saponin glycoside at m/z 1445.64 [M + formic-H]- equivalent to C64H104O33 and the putatively found active metabolite at m/z 1283.58 [M + formic-H]- corresponding to scillanoside L-1. A combination of metabolomics and bioactivity-guided approaches resulted in the isolation of a norlanostane-type saponin glycoside with antitrypanosomal activity of 98.9% inhibition at 20 µM. PMID: 30796274 [PubMed - in process]

Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma.

Sun, 24/02/2019 - 14:35
Related Articles Function, Detection and Alteration of Acylcarnitine Metabolism in Hepatocellular Carcinoma. Metabolites. 2019 Feb 21;9(2): Authors: Li S, Gao D, Jiang Y Abstract Acylcarnitines play an essential role in regulating the balance of intracellular sugar and lipid metabolism. They serve as carriers to transport activated long-chain fatty acids into mitochondria for β-oxidation as a major source of energy for cell activities. The liver is the most important organ for endogenous carnitine synthesis and metabolism. Hepatocellular carcinoma (HCC), a primary malignancy of the live with poor prognosis, may strongly influence the level of acylcarnitines. In this paper, the function, detection and alteration of acylcarnitine metabolism in HCC were briefly reviewed. An overview was provided to introduce the metabolic roles of acylcarnitines involved in fatty acid β-oxidation. Then different analytical platforms and methodologies were also briefly summarised. The relationship between HCC and acylcarnitine metabolism was described. Many of the studies reported that short, medium and long-chain acylcarnitines were altered in HCC patients. These findings presented current evidence in support of acylcarnitines as new candidate biomarkers for studies on the pathogenesis and development of HCC. Finally we discussed the challenges and perspectives of exploiting acylcarnitine metabolism and its related metabolic pathways as a target for HCC diagnosis and prognosis. PMID: 30795537 [PubMed]

metabolomics; +42 new citations

Sat, 23/02/2019 - 14:14
42 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 2019/02/23PubMed comprises more than millions of 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.

Comprehensive mass spectrometry-guided plant specialized metabolite phenotyping reveals metabolic diversity in the cosmopolitan plant family Rhamnaceae.

Thu, 21/02/2019 - 13:45
Related Articles Comprehensive mass spectrometry-guided plant specialized metabolite phenotyping reveals metabolic diversity in the cosmopolitan plant family Rhamnaceae. Plant J. 2019 Feb 20;: Authors: Kang KB, Ernst M, van der Hooft JJJ, da Silva RR, Park J, Medema MH, Sung SH, Dorrestein PC Abstract Plants produce a myriad of specialized metabolites to overcome their sessile habit and combat biotic as well as abiotic stresses. Evolution has shaped specialized metabolite diversity, which drives many other aspects of plant biodiversity. However, until recently, large-scale studies investigating specialized metabolite diversity in an evolutionary context have been limited by the impossibility to identify chemical structures of hundreds to thousands of compounds in a time-feasible manner. Here, we introduce a workflow for large-scale, semi-automated annotation of specialized metabolites, and apply it for over 1000 metabolites of the cosmopolitan plant family Rhamnaceae. We enhance the putative annotation coverage dramatically, from 2.5% based on spectral library matches alone to 42.6% of total MS/MS molecular features extending annotations from well-known plant compound classes into the dark plant metabolomics matter. To gain insights in substructural diversity within the plant family, we also extract patterns of co-occurring fragments and neutral losses, so-called Mass2Motifs, from the dataset; for example, only the Ziziphoid clade developed the triterpenoid biosynthetic pathway, whereas the Rhamnoid clade predominantly developed diversity in flavonoid glycosides, including 7-O-methyltransferase activity. Our workflow provides the foundations towards the automated, high-throughput chemical identification of massive metabolite spaces, and we expect it to revolutionize our understanding of plant chemoevolutionary mechanisms. This article is protected by copyright. All rights reserved. PMID: 30786088 [PubMed - as supplied by publisher]

Metabolomic profiling reveals correlations between spermiogram parameters and the metabolites present in human spermatozoa and seminal plasma.

Thu, 21/02/2019 - 13:45
Related Articles Metabolomic profiling reveals correlations between spermiogram parameters and the metabolites present in human spermatozoa and seminal plasma. PLoS One. 2019;14(2):e0211679 Authors: Engel KM, Baumann S, Rolle-Kampczyk U, Schiller J, von Bergen M, Grunewald S Abstract In 50% of all infertility cases, the male is subfertile or infertile, however, the underlying mechanisms are often unknown. Even when assisted reproductive procedures such as in vitro fertilization and intracytoplasmic sperm injection are performed, the causes of male factor infertility frequently remain elusive. Since the overall activity of cells is closely linked to their metabolic capacity, we analyzed a panel of 180 metabolites in human sperm and seminal plasma and elucidated their associations with spermiogram parameters. Therefore, metabolites from a group of 20 healthy donors were investigated using a targeted LC-MS/MS approach. The correlation analyses of the amino acids, biogenic amines, acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins and sugars from sperm and seminal plasma with standard spermiogram parameters revealed that metabolites in sperm are closely related to sperm motility, whereas those in seminal plasma are closely related to sperm concentration and morphology. This study provides essential insights into the metabolome of human sperm and seminal plasma and its associations with sperm functions. This metabolomics technique could be a promising screening tool to detect the factors of male infertility in cases where the cause of infertility is unclear. PMID: 30785892 [PubMed - in process]

Pyrophosphate modulates plant stress responses via SUMOylation.

Thu, 21/02/2019 - 13:45
Related Articles Pyrophosphate modulates plant stress responses via SUMOylation. Elife. 2019 Feb 20;8: Authors: Patir-Nebioglu MG, Andrés Z, Krebs M, Fink F, Drzewicka K, Stankovic-Valentin N, Segami S, Schuck S, Büttner M, Hell R, Maeshima M, Melchior F, Schumacher K Abstract Pyrophosphate (PPi), a byproduct of macromolecule biosynthesis is maintained at low levels by soluble inorganic pyrophosphatases (sPPase) found in all eukaryotes. In plants, H+-pumping pyrophosphatases (H+-PPase) convert the substantial energy present in PPi into an electrochemical gradient. We show here, that both cold- and heat stress sensitivity of fugu5 mutants lacking the major H+-PPase isoform AVP1 is correlated with reduced SUMOylation. In addition, we show that increased PPi concentrations interfere with SUMOylation in yeast and we provide evidence that SUMO activating E1-enzymes are inhibited by micromolar concentrations of PPi in a non-competitive manner. Taken together, our results do not only provide a mechanistic explanation for the beneficial effects of AVP1 overexpression in plants but they also highlight PPi as an important integrator of metabolism and stress tolerance. PMID: 30785397 [PubMed - in process]

The effect of vegetable and spice addition on the acrylamide content and antioxidant activity of innovative cereal products.

Thu, 21/02/2019 - 13:45
Related Articles The effect of vegetable and spice addition on the acrylamide content and antioxidant activity of innovative cereal products. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2019 Feb 20;:1-11 Authors: Jaworska D, Mojska H, Gielecińska I, Najman K, Gondek E, Przybylski W, Krzyczkowska P Abstract The aim of the work was to assess the impact of vegetable and spice addition on the acrylamide content and antioxidant activity of extruded cereal crisps. The foods were based on grain ingredients, such as brown rice, whole grain flour, wheat bran, with different vegetables. Products from one group contained green vegetables, such as broccoli and zucchini; garlic was included as a flavour additive (0.75-1.50%). The second group of crisps consisted of similar cereal ingredients with pumpkin and cinnamon; additionally ginger was included as a flavour additive (0.75-1.50%). The results indicate that the production of a new, innovative product with appropriate nutritional value and acceptable quality is a complex process. The production process significantly changed the nutritional value of the product. The content of acrylamide in zucchini and broccoli crisps was relatively low; ranging from 78 to 86 μg/kg of product. The addition of garlic did not significantly affect the acrylamide content in the final product. For cereal-pumpkin crisps, the acrylamide content was 7 times higher in comparison with zucchini and broccoli products. The acrylamide content in pumpkin and ginger crisps exceeded the benchmark level. The antioxidant activity of the pumpkin product was significantly higher (p < 0.05) than for crisps with green vegetables. PMID: 30785367 [PubMed - as supplied by publisher]

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