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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 1 hour 12 min ago

Cardiac metabolomics and autopsy in a patient with early diffuse systemic sclerosis presenting with dyspnea: a case report.

Wed, 10/06/2015 - 13:34
Related Articles Cardiac metabolomics and autopsy in a patient with early diffuse systemic sclerosis presenting with dyspnea: a case report. J Med Case Rep. 2015 Jun 10;9(1):136 Authors: Frech TM, Revelo MP, Ryan JJ, Shah AA, Gordon J, Domsic R, Hant F, Assassi S, Shanmugam VK, Hinchcliff M, Steen V, Khanna D, Bernstein EJ, Cox J, Luem N, Drakos S Abstract INTRODUCTION: Diffuse systemic sclerosis is associated with high mortality; however, the pathogenesis of cardiac death in these patients is not clear. CASE PRESENTATION: A 56-year-old Caucasian female patient presented with dyspnea and requested to donate her body to science in order to improve understanding of diffuse systemic sclerosis pathogenesis. She had extensive testing for dyspnea including pulmonary function tests, an echocardiogram, cardiac magnetic resonance imaging, and right heart catheterization to characterize her condition. Her case highlights the morbidity seen in this disease, including the presence of extensive skin thickening, digital ulcerations, and scleroderma renal crisis. CONCLUSION: In this case report, we present the finding of cardiac tissue metabolomics, which may indicate a problem with vasodilation as a contributor to cardiac death in diffuse systemic sclerosis. The use of autopsy and tissue metabolomics in rare disease may help clarify disease pathogenesis. PMID: 26055398 [PubMed - as supplied by publisher]

Delving deeper into technological innovations to understand differences in rice quality.

Wed, 10/06/2015 - 13:34
Related Articles Delving deeper into technological innovations to understand differences in rice quality. Rice (N Y). 2015 Dec;8(1):43 Authors: Calingacion M, Fang L, Quiatchon-Baeza L, Mumm R, Riedel A, Hall RD, Fitzgerald M Abstract Increasing demand for better quality rice varieties, which are also more suited to growth under sub-optimal cultivation conditions, is driving innovation in rice research. Here we have used a multi-disciplinary approach, involving SNP-based genotyping together with phenotyping based on yield analysis, metabolomic analysis of grain volatiles, and sensory panel analysis to determine differences between two contrasting rice varieties, Apo and IR64. Plants were grown under standard and drought-induced conditions. Results revealed important differences between the volatile profiles of the two rice varieties and we relate these differences to those perceived by the sensory panel. Apo, which is the more drought tolerant variety, was less affected by the drought condition concerning both sensory profile and yield; IR64, which has higher quality but is drought sensitive, showed greater differences in these characteristics in response to the two growth conditions. Metabolomics analyses using GCxGC-MS, followed by multivariate statistical analyses of the data, revealed a number of discriminatory compounds between the varieties, but also effects of the difference in cultivation conditions. Results indicate the complexity of rice volatile profile, even of non-aromatic varieties, and how metabolomics can be used to help link changes in aroma profile with the sensory phenotype. Our outcomes also suggest valuable multi-disciplinary approaches which can be used to help define the aroma profile in rice, and its underlying genetic background, in order to support breeders in the generation of improved rice varieties combining high yield with high quality, and tolerance of both these traits to climate change. PMID: 26054242 [PubMed]

Harnessing the heart of big data.

Wed, 10/06/2015 - 13:34
Related Articles Harnessing the heart of big data. Circ Res. 2015 Mar 27;116(7):1115-9 Authors: Scruggs SB, Watson K, Su AI, Hermjakob H, Yates JR, Lindsey ML, Ping P PMID: 25814682 [PubMed - indexed for MEDLINE]

Surveillance for lower airway pathogens in mechanically ventilated patients by metabolomic analysis of exhaled breath: a case-control study.

Wed, 10/06/2015 - 13:34
Related Articles Surveillance for lower airway pathogens in mechanically ventilated patients by metabolomic analysis of exhaled breath: a case-control study. Thorax. 2015 Apr;70(4):320-5 Authors: Fowler SJ, Basanta-Sanchez M, Xu Y, Goodacre R, Dark PM Abstract BACKGROUND: Healthcare associated infections, including ventilator associated pneumonia, are difficult to diagnose and treat, and are associated with significant morbidity, mortality and cost. We aimed to demonstrate proof of concept that breath volatile profiles were associated with the presence of clinically relevant pathogens in the lower respiratory tract. METHODS: Patients with sterile brain injury requiring intubation and ventilation on the intensive care unit were eligible for inclusion. Serial clinical and breath data were obtained three times a week, from admission up to a maximum of 10 days. Bronchial lavage for semiquantitative culture was collected immediately prior to breath sampling. Breath samples were collected in triplicate for off-line analysis by thermal-desorption/gas chromatography/time-of-flight mass spectrometry. Breath data were recorded as retention time/mass ion pairs, and analysed (pathogen present vs absent) by ANOVA-mean centre principal component analysis. RESULTS: Samples were collected from 46 patients (mean (SD) age 49 (19) years; 27 male). The dominant factors affecting breath sample analysis were the individual breath profile and duration of intubation. When these were taken into account, clear separation was seen between breath profiles at each time point by the presence/absence of pathogens. Loadings plots identified consistent metabolite peaks contributing to this separation at each time point. CONCLUSIONS: Breath volatile analysis is able to classify breath profiles of patients with and without significant pathogen load in the lower respiratory tract. If validated in independent cohorts, these findings could lead to development of rapid non-invasive point-of-care surveillance systems and diagnostics for lower respiratory tract infection in the intensive care unit. PMID: 25661115 [PubMed - indexed for MEDLINE]

Successful treatment of Cronkhite-Canada syndrome using anti-tumor necrosis factor antibody therapy.

Wed, 10/06/2015 - 13:34
Related Articles Successful treatment of Cronkhite-Canada syndrome using anti-tumor necrosis factor antibody therapy. Endoscopy. 2014;46 Suppl 1 UCTN:E476-7 Authors: Watanabe D, Ooi M, Hoshi N, Kohashi M, Yoshie T, Ikehara N, Yoshida M, Yanagita E, Yamasaki T, Itoh T, Azuma T PMID: 25314205 [PubMed - indexed for MEDLINE]

[Analyzing the inhibition of vitamin B12 to dexamethasone-induced palatognathous mouse using 1H-nuclear magnetic resonance based metabonomics method].

Wed, 10/06/2015 - 13:34
Related Articles [Analyzing the inhibition of vitamin B12 to dexamethasone-induced palatognathous mouse using 1H-nuclear magnetic resonance based metabonomics method]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2010 Jun;28(3):311-4 Authors: Wu XH, Huang H, Xu B, Zhou JL, Kong XL, Shi B, Huang J, Li W Abstract OBJECTIVE: Metabonomic analysis has been increasingly used to monitor metabolic abnormalities in cells and their micro-environment in order to detect the biomarkers recently. This study evaluated the feasibility of applying 1H-nuclear magnetic resonance (1H-NMR) based metabonomic method to detect the differences of the early development of cleft palate in the plasma from control group and experimental group. METHODS: Pregnant mice (inbred C57BL/6J strain) with vitamin B12 injected only were assigned as the control group, pregnant mice with excessive Dex, injected after vitamin B12 as the experimental group, each group includes 12 mice. And the effect of B12 to rate of cleft palate was observed. The technology of nuclear magnetic resonance (NMR) was used to detect the endogenous small molecule metabolites. Finally, changes of metabolites ingredients were ascertained by using the method of principal component analysis (PCA). RESULTS: There was significant difference in PCA scores plot between the two groups according to whether cleft palate occurred. CONCLUSION: The 1H-NMR based metabonomic approach might be used as a feasible and efficient method for a deep exploration of the pathogenesis of cleft lip and palate and an early exploration of the mechanism of vitamin B12. PMID: 20635665 [PubMed - indexed for MEDLINE]

Future perspectives in Orbitrap™ high resolution mass spectrometry in food analysis - a review.

Tue, 09/06/2015 - 12:15
Future perspectives in Orbitrap™ high resolution mass spectrometry in food analysis - a review. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2015 Jun 8; Authors: Senyuva HZ, Gokmen V, Sarikaya EA Abstract We have conducted a literature search from 2007-2014 to identify publications where principally LC-Orbitrap™ high resolution mass spectrometry (HRMS) has been employed in food analysis. Of a total of 212 relevant references, only 22 papers were from the years 2007-2010, but in subsequent years there has been a steady growth in publications with 38 to 55 relevant papers being published each year from 2011-2014. In the food safety area over 50% of the published papers were equally divided between pesticides, veterinary drug residues and natural toxins (including mycotoxins) focussed primarily on multi-analyte target analysis. LC- Orbitrap™ HRMS was also found to be increasingly important for the analysis of bioactive substances, principally phenolic compounds in foods. A number of studies reported for the first time the identification of new fungal metabolites, predominantly various conjugated forms of known mycotoxins. Novel process contaminants were also identified by LC-Orbitrap™ HRMS, as were various substances used for food adulteration and bioactive substances in herbal products and dietary supplements. Untargeted analysis is seen as a major future trend where HRMS plays a significant role. Retrospective analysis of scanned HR mass spectra in conjunction with relevant databases can provide new insights. Metabolomics is also being increasingly used where foods are being profiled through fingerprinting using HRMS. All evidence points towards future growth in the number of applications of HRMS in food safety and quality, as the power of this technique gains wider recognition. PMID: 26053336 [PubMed - as supplied by publisher]

ONION: Functional Approach for Integration of Lipidomics and Transcriptomics Data.

Tue, 09/06/2015 - 12:15
ONION: Functional Approach for Integration of Lipidomics and Transcriptomics Data. PLoS One. 2015;10(6):e0128854 Authors: Piwowar M, Jurkowski W Abstract To date, the massive quantity of data generated by high-throughput techniques has not yet met bioinformatics treatment required to make full use of it. This is partially due to a mismatch in experimental and analytical study design but primarily due to a lack of adequate analytical approaches. When integrating multiple data types e.g. transcriptomics and metabolomics, multidimensional statistical methods are currently the techniques of choice. Typical statistical approaches, such as canonical correlation analysis (CCA), that are applied to find associations between metabolites and genes are failing due to small numbers of observations (e.g. conditions, diet etc.) in comparison to data size (number of genes, metabolites). Modifications designed to cope with this issue are not ideal due to the need to add simulated data resulting in a lack of p-value computation or by pruning of variables hence losing potentially valid information. Instead, our approach makes use of verified or putative molecular interactions or functional association to guide analysis. The workflow includes dividing of data sets to reach the expected data structure, statistical analysis within groups and interpretation of results. By applying pathway and network analysis, data obtained by various platforms are grouped with moderate stringency to avoid functional bias. As a consequence CCA and other multivariate models can be applied to calculate robust statistics and provide easy to interpret associations between metabolites and genes to leverage understanding of metabolic response. Effective integration of lipidomics and transcriptomics is demonstrated on publically available murine nutrigenomics data sets. We are able to demonstrate that our approach improves detection of genes related to lipid metabolism, in comparison to applying statistics alone. This is measured by increased percentage of explained variance (95% vs. 75-80%) and by identifying new metabolite-gene associations related to lipid metabolism. PMID: 26053255 [PubMed - as supplied by publisher]

Resolution-enhanced 2D NMR of complex mixtures by non-uniform sampling.

Tue, 09/06/2015 - 12:15
Resolution-enhanced 2D NMR of complex mixtures by non-uniform sampling. Magn Reson Chem. 2015 Jun 6; Authors: Le Guennec A, Dumez JN, Giraudeau P, Caldarelli S Abstract NMR is a powerful tool for the analysis of complex mixtures and the identification of individual components. Two-dimensional (2D) NMR potentially offers a wealth of information, but resolution is often sacrificed in order to contain experimental times. We explore the use of non-uniform sampling (NUS) to increase substantially the resolution of 2D NMR spectra of complex mixtures of small molecules, with no increase in experimental time. Two common pulse sequences for metabolomics applications are analysed, HSQC and TOCSY. Specific attention is paid to sensitivity in resolution-enhanced NUS spectra, using the signal-to-maximum-noise ratio as a metric. With a careful choice of sampling schedule and reconstruction algorithm, resolution in the (13) C dimension for HSQC is increased by a factor of at least 32, with no loss in sensitivity and no spurious peaks. For TOCSY, multiplets can be resolved in the indirect dimension in a reasonable experimental time. These properties should increase the usefulness of 2D NMR for metabolomics applications by, for example, increasing the chances of metabolite identification. Copyright © 2015 John Wiley & Sons, Ltd. PMID: 26053155 [PubMed - as supplied by publisher]

Identification of a transporter Slr0982 involved in ethanol tolerance in cyanobacterium Synechocystis sp. PCC 6803.

Tue, 09/06/2015 - 12:15
Identification of a transporter Slr0982 involved in ethanol tolerance in cyanobacterium Synechocystis sp. PCC 6803. Front Microbiol. 2015;6:487 Authors: Zhang Y, Niu X, Shi M, Pei G, Zhang X, Chen L, Zhang W Abstract Cyanobacteria have been engineered to produce ethanol through recent synthetic biology efforts. However, one major challenge to the cyanobacterial systems for high-efficiency ethanol production is their low tolerance to the ethanol toxicity. With a major goal to identify novel transporters involved in ethanol tolerance, we constructed gene knockout mutants for 58 transporter-encoding genes of Synechocystis sp. PCC 6803 and screened their tolerance change under ethanol stress. The efforts allowed discovery of a mutant of slr0982 gene encoding an ATP-binding cassette transporter which grew poorly in BG11 medium supplemented with 1.5% (v/v) ethanol when compared with the wild type, and the growth loss could be recovered by complementing slr0982 in the Δslr0982 mutant, suggesting that slr0982 is involved in ethanol tolerance in Synechocystis. To decipher the tolerance mechanism involved, a comparative metabolomic and network-based analysis of the wild type and the ethanol-sensitive Δslr0982 mutant was performed. The analysis allowed the identification of four metabolic modules related to slr0982 deletion in the Δslr0982 mutant, among which metabolites like sucrose and L-pyroglutamic acid which might be involved in ethanol tolerance, were found important for slr0982 deletion in the Δslr0982 mutant. This study reports on the first transporter related to ethanol tolerance in Synechocystis, which could be a useful target for further tolerance engineering. In addition, metabolomic and network analysis provides important findings for better understanding of the tolerance mechanism to ethanol stress in Synechocystis. PMID: 26052317 [PubMed]

Generalized adaptive intelligent binning of multiway data.

Tue, 09/06/2015 - 12:15
Generalized adaptive intelligent binning of multiway data. Chemometr Intell Lab Syst. 2015 Aug;146:42-46 Authors: Worley B, Powers R Abstract NMR metabolic fingerprinting methods almost exclusively rely upon the use of one-dimensional (1D) (1)H NMR data to gain insights into chemical differences between two or more experimental classes. While 1D (1)H NMR spectroscopy is a powerful, highly informative technique that can rapidly and nondestructively report details of complex metabolite mixtures, it suffers from significant signal overlap that hinders interpretation and quantification of individual analytes. Two-dimensional (2D) NMR methods that report heteronuclear connectivities can reduce spectral overlap, but their use in metabolic fingerprinting studies is limited. We describe a generalization of Adaptive Intelligent binning that enables its use on multidimensional datasets, allowing the direct use of nD NMR spectroscopic data in bilinear factorizations such as principal component analysis (PCA) and partial least squares (PLS). PMID: 26052171 [PubMed - as supplied by publisher]

The Aspergillus fumigatus Septins Play Pleiotropic Roles in Septation, Conidiation, and Cell Wall Stress, but are Dispensable for Virulence.

Tue, 09/06/2015 - 12:15
The Aspergillus fumigatus Septins Play Pleiotropic Roles in Septation, Conidiation, and Cell Wall Stress, but are Dispensable for Virulence. Fungal Genet Biol. 2015 Jun 4; Authors: Vargas-Muñiz JM, Renshaw H, Richards AD, Lamoth F, Soderblom EJ, Arthur Moseley M, Juvvadi PR, Steinbach WJ Abstract Septins are a conserved family of GTPases that regulate important cellular processes such as cell wall integrity, and septation in fungi. The requirement of septins for virulence has been demonstrated in the human pathogenic yeasts Candida albicans and Cryptococcus neoformans, as well as the plant pathogen Magnaporthe oryzae. Aspergillus spp. contains five genes encoding for septins (aspA-E). While the importance of septins AspA, AspB, AspC, and AspE for growth and conidiation has been elucidated in the filamentous fungal model Aspergillus nidulans, nothing is known on the role of septins in growth and virulence in the human pathogen Aspergillus fumigatus. Here we deleted all five A. fumigatus septins, and generated certain double and triple septin deletion strains. Phenotypic analyses revealed that while all the septins are dispensable in normal growth conditions, AspA, AspB, AspC and AspE are required for regular septation. Furthermore, deletion of only the core septin genes significantly reduced conidiation. Concomitant with the absence of an electron-dense outer conidial wall, the ΔaspB strain was also sensitive to anti-cell wall agents. Infection with the ΔaspB strain in a Galleria mellonella model of invasive aspergillosis showed hypervirulence, but no virulence difference was noted when compared to the wild-type strain in a murine model of invasive aspergillosis. Although the deletion of aspB resulted in increased release of TNF-α from the macrophages, no significant inflammation differences in lung histology was noted between the ΔaspB strain and the wild-type strain. Taken together, these results point to the importance of septins in A. fumigatus growth, but not virulence in a murine model. PMID: 26051489 [PubMed - as supplied by publisher]

What the transcriptome does not tell - proteomics and metabolomics are closer to the plants' patho-phenotype.

Tue, 09/06/2015 - 12:15
What the transcriptome does not tell - proteomics and metabolomics are closer to the plants' patho-phenotype. Curr Opin Plant Biol. 2015 Jun 3;26:26-31 Authors: Feussner I, Polle A Abstract The proteome and metabolome of the plant provide a wealth of additional information on plant-microbe interactions since they not only represent additional levels of regulation, but often they harbor the end products of regulatory processes. Proteomics has contributed to our understanding of plant-microbe research by increasing the spatial resolution of the analysis within the infected tissue, because components of the basal immunity were uncovered in the apoplast. Metabolomics has developed into a powerful approach to discover the role of small molecules during plant-microbe interactions in non-model plants since it does not depend on the availability of genome or transcriptome data. Moreover, novel molecules involved in systemic acquired resistance and the precursors for the formation of molecules that provide physical barriers to prevent spreading of pathogens were identified. PMID: 26051215 [PubMed - as supplied by publisher]

Heart Failure in Non-Caucasians, Women, and Older Adults: A White Paper on Special Populations from the Heart Failure Society of America Guideline Committee.

Tue, 09/06/2015 - 12:15
Heart Failure in Non-Caucasians, Women, and Older Adults: A White Paper on Special Populations from the Heart Failure Society of America Guideline Committee. J Card Fail. 2015 Jun 4; Authors: Colvin-Adams M, Sweitzer NK, Albert NM, Krishnamani R, Rich MW, Stough WG, Walsh MN, Westlake Canary CA, Allen LA, Bonnell MR, Carson PE, Chan MC, Dickinson MG, Dries DL, Ewald GA, Fang JC, Hernandez AF, Hershberger RE, Katz SD, Moore S, Rodgers JE, Rogers JG, Vest AR, Whellan DJ, Givertz MM Abstract The presentation, natural history, clinical outcomes, and response to therapy in patients with heart failure differ in some ways across populations. Women, older adults, and non-Caucasian racial or ethnic groups comprise a substantial proportion of the overall heart failure population, but they have typically been underrepresented in clinical trials. As a result, uncertainty exists about the efficacy of some guideline-directed medical therapies and devices in specific populations, which may result in the under or over treatment of these patients. Even when guideline-based treatments are prescribed, socioeconomic, physical, or psychological factors may impact non-Caucasian and older adult patient groups to a different extent and impact the application, effectiveness, and tolerability of these therapies. Individualized therapy based on tailored biology (genetics, proteomics, metabolomics), socioeconomic and cultural considerations, and individual goals and preferences may be the optimal approach for managing diverse patients. This comprehensive approach to personalized medicine is evolving, but in the interim, the scientific community should continue focused efforts on intensifying research in special populations, prescribing guideline directed medical therapy unless contraindicated, and implementing evidence-based strategies including patient education and multidisciplinary teams in the management of patients. PMID: 26051012 [PubMed - as supplied by publisher]

Metabolomics analysis of cervical cancer, cervical intraepithelial neoplasia and chronic cervicitis by 1H NMR spectroscopy.

Tue, 09/06/2015 - 12:15
Metabolomics analysis of cervical cancer, cervical intraepithelial neoplasia and chronic cervicitis by 1H NMR spectroscopy. Eur J Gynaecol Oncol. 2015;36(2):174-80 Authors: Ye N, Liu C, Shi P Abstract Metabolomics profiles of serum samples from women with chronic cervicitis, cervical intraepithelial neoplasia (CIN), and cervical cancer were characterized by proton nuclear magnetic resonance (1H NMR). These spectral profiles were subjected to partial least-squares discriminant analysis (PLS-DA), and good discriminations between cancerand non-cancer groups (chronic cervicitis and CIN) were achieved by multivariate modeling of serum profiles. The main metabolites contributing to these discriminations, as highlighted by multivariate analysis and confirmed by spectral integration, were formate, tyrosine, β-glucose, inositol, glycine, carnitine, glutamine, acetate, alanine, valine, isoleucine, and very-low-density lipoprotein (VLDL). Metabolomics analysis for chronic cervicitis, CIN, and cervical cancer is significant, which give a systemic metabolic response of these female diseases. The systemic metabolic response may be used to identify the potential biomarkers for the diseases. PMID: 26050356 [PubMed - in process]

A metabolomic strategy to screen the prototype components and metabolites of Qingkailing injection in rat urine by high-performance liquid chromatography with tandem mass spectrometry.

Tue, 09/06/2015 - 12:15
Related Articles A metabolomic strategy to screen the prototype components and metabolites of Qingkailing injection in rat urine by high-performance liquid chromatography with tandem mass spectrometry. J Sep Sci. 2014 Oct;37(20):2844-50 Authors: Guo M, Zhang L, Liu H, Qin L, Zhang Z, Bai X, Gao X Abstract Xenobiotic metabolome identification of Chinese herbal formula in biological systems is a very challenging task. Qingkailing injection is a typical Chinese herbal injection, which is wildly used clinically in China. However, the holistic metabolic fate of the ingredient from Qingkailing injection remains unclear. In this work, a metabolomic strategy for comprehensively elucidating Qingkailing injection derived prototype components and metabolites in rat urine conducted by hybrid linear ion trap high-resolution mass spectrometry was developed. High-performance liquid chromatography coupled with hybrid linear ion trap high-resolution mass spectrometry was developed to obtain the urine profiling between the control group and Qingkailing injection treated group. Orthogonal partial least squares discriminate analysis was applied to distinguish the exogenous and the endogenous. In the S-plot, 37 xenobiotics derived from Qingkailing injection were found in urine, including 18 prototype compounds and 19 metabolites. The characterization of the prototype components and metabolites in rat's urine provided essential data for further pharmacological studies of Qingkailing injection. Our results indicated that the metabolomic approach was an effective tool to discover, screen, and analyze the multiple prototype components and their metabolites from complicated traditional Chinese preparations in vivo. PMID: 25073714 [PubMed - indexed for MEDLINE]

Intermediate-type vancomycin resistance (VISA) in genetically-distinct Staphylococcus aureus isolates is linked to specific, reversible metabolic alterations.

Tue, 09/06/2015 - 12:15
Related Articles Intermediate-type vancomycin resistance (VISA) in genetically-distinct Staphylococcus aureus isolates is linked to specific, reversible metabolic alterations. PLoS One. 2014;9(5):e97137 Authors: Alexander EL, Gardete S, Bar HY, Wells MT, Tomasz A, Rhee KY Abstract Intermediate (VISA-type) vancomycin resistance in Staphylococcus aureus has been associated with a range of physiologic and genetic alterations. Previous work described the emergence of VISA-type resistance in two clonally-distinct series of isolates. In both series (the first belonging to MRSA clone ST8-USA300, and the second to ST5-USA100), resistance was conferred by a single mutation in yvqF (a negative regulator of the vraSR two-component system associated with vancomycin resistance). In the USA300 series, resistance was reversed by a secondary mutation in vraSR. In this study, we combined systems-level metabolomic profiling with statistical modeling techniques to discover specific, reversible metabolic alterations associated with the VISA phenotype. PMID: 24817125 [PubMed - indexed for MEDLINE]

Evidence supporting distinct functions of three cytosolic glutamine synthetases and two NADH-glutamate synthases in rice.

Tue, 09/06/2015 - 12:15
Related Articles Evidence supporting distinct functions of three cytosolic glutamine synthetases and two NADH-glutamate synthases in rice. J Exp Bot. 2014 Oct;65(19):5519-25 Authors: Yamaya T, Kusano M Abstract The functions of the three isoenzymes of cytosolic glutamine synthetase (GS1;1, GS1;2, and GS1;3) and two NADH-glutamate synthases (NADH-GOGAT1 and NADH-GOGAT2) in rice (Oryza sativa L.) were characterized using a reverse genetics approach and spatial expression of the corresponding genes. OsGS1;2 and OsNADH-GOGAT1 were mainly expressed in surface cells of rice roots in an NH4 (+)-dependent manner. Disruption of either gene by the insertion of endogenous retrotransposon Tos17 caused reduction in active tiller number and hence panicle number at harvest. Re-introduction of OsGS1;2 cDNA under the control of its own promoter into the knockout mutants successfully restored panicle number to wild-type levels. These results indicate that GS1;2 and NADH-GOGAT1 are important in the primary assimilation of NH4 (+) taken up by rice roots. OsGS1;1 and OsNADH-GOGAT2 were mainly expressed in vascular tissues of mature leaf blades. OsGS1;1 mutants showed severe reduction in growth rate and grain filling, whereas OsNADH-GOGAT2 mutants had marked reduction in spikelet number per panicle. Complementation of phenotypes seen in the OsGS1;1 mutant was successfully observed when OsGS1;1 was re-introduced. Thus, these two enzymes could be important in remobilization of nitrogen during natural senescence. Metabolite profiling data showed a crucial role of GS1;1 in coordinating metabolic balance in rice. Expression of OsGS1:3 was spikelet-specific, indicating that it is probably important in grain ripening and/or germination. Thus, these isoenzymes seem to possess distinct and non-overlapping functions and none was able to compensate for the individual function of another. PMID: 24634487 [PubMed - indexed for MEDLINE]

Sex hormone-binding globulin associations with circulating lipids and metabolites and the risk for type 2 diabetes: observational and causal effect estimates.

Mon, 08/06/2015 - 14:29
Sex hormone-binding globulin associations with circulating lipids and metabolites and the risk for type 2 diabetes: observational and causal effect estimates. Int J Epidemiol. 2015 Jun 6; Authors: Wang Q, Kangas AJ, Soininen P, Tiainen M, Tynkkynen T, Puukka K, Ruokonen A, Viikari J, Kähönen M, Lehtimäki T, Salomaa V, Perola M, Davey Smith G, Raitakari OT, Järvelin MR, Würtz P, Kettunen J, Ala-Korpela M Abstract BACKGROUND: The causal role of circulating sex hormone-binding globulin (SHBG) for type 2 diabetes is controversial. Information on the relations between SHBG and new biomarkers of cardiometabolic risk is scarce. METHODS: We applied quantitative nuclear magnetic resonance metabolomics in three Finnish population-based cohorts to comprehensively profile circulating lipids and metabolites and study their associations with SHBG. Mendelian randomization was used to examine potential causality of SHBG on the metabolic measures and insulin resistance. Prospective associations and causal effect estimates of SHBG on type 2 diabetes were assessed via meta-analysis including summary statistics from the DIAGRAM consortium. RESULTS: In cross-sectional analysis in 6475 young adults (mean age 31, 57% men), higher SHBG was linked with a more favourable cardiometabolic risk profile, including associations with lipoprotein subclasses, fatty acid composition, amino acids, ketone bodies and inflammation-linked glycoproteins. Prospective analysis of 1377 young adults with 6-year follow-up indicated that SHBG is also associated with future insulin resistance. Mendelian randomization suggested only minor, if any, causal effects of SHBG on lipid and metabolite measures and insulin resistance(n = 10 895).Causal effect estimates on type 2 diabetes for 41 439 cases and 103 870 controls indicated a causative protective role of SHBG (OR = 0.83 per 1-SD, 95% CI: 0.76, 0.91); however, effects were considerably weaker than observed in meta-analysis of prospective studies [hazard ratio (HR) = 0.47 per 1-SD, 95% CI: 0.41, 0.53]. CONCLUSION: Circulating SHBG is strongly associated with systemic metabolism and predictive for insulin resistance and diabetes. The weaker causal estimates suggest that the observational associations are partly confounded rather than conferred directly via circulating SHBG. PMID: 26050255 [PubMed - as supplied by publisher]

Metabolomics and renal disease.

Mon, 08/06/2015 - 14:29
Metabolomics and renal disease. Curr Opin Nephrol Hypertens. 2015 Jul;24(4):371-379 Authors: Rhee EP Abstract PURPOSE OF REVIEW: This review summarizes recent metabolomics studies of renal disease, outlining some of the limitations of the literature to date. RECENT FINDINGS: The application of metabolomics in nephrology research has expanded from the initial analyses of uremia to include both cross-sectional and longitudinal studies of earlier stages of kidney disease. Although these studies have nominated several potential markers of incident chronic kidney disease (CKD) and CKD progression, a lack of overlap in metabolite coverage has limited the ability to synthesize results across groups. Furthermore, direct examination of renal metabolite handling has underscored the substantial impact kidney function has on these potential markers (and many other circulating metabolites). In experimental studies, metabolomics has been used to identify a signature of decreased mitochondrial function in diabetic nephropathy and a preference for aerobic glucose metabolism in polycystic kidney disease. In each case, these studies have outlined novel therapeutic opportunities. Finally, as a complement to the longstanding interest in renal metabolite clearance, the microbiome has been increasingly recognized as the source of many plasma metabolites, including some with potential functional relevance to CKD and its complications. SUMMARY: The high-throughput, high-resolution phenotyping enabled by metabolomics technologies has begun to provide insight on renal disease in clinical, physiologic, and experimental contexts. PMID: 26050125 [PubMed - as supplied by publisher]

Pages