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

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]

A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control.

Mon, 08/06/2015 - 14:29
A systems view of type 2 diabetes-associated metabolic perturbations in saliva, blood and urine at different timescales of glycaemic control. Diabetologia. 2015 Jun 7; Authors: Yousri NA, Mook-Kanamori DO, Selim MM, Takiddin AH, Al-Homsi H, Al-Mahmoud KA, Karoly ED, Krumsiek J, Do KT, Neumaier U, Mook-Kanamori MJ, Rowe J, Chidiac OM, McKeon C, Al Muftah WA, Kader SA, Kastenmüller G, Suhre K Abstract AIMS/HYPOTHESIS: Metabolomics has opened new avenues for studying metabolic alterations in type 2 diabetes. While many urine and blood metabolites have been associated individually with diabetes, a complete systems view analysis of metabolic dysregulations across multiple biofluids and over varying timescales of glycaemic control is still lacking. METHODS: Here we report a broad metabolomics study in a clinical setting, covering 2,178 metabolite measures in saliva, blood plasma and urine from 188 individuals with diabetes and 181 controls of Arab and Asian descent. Using multivariate linear regression we identified metabolites associated with diabetes and markers of acute, short-term and long-term glycaemic control. RESULTS: Ninety-four metabolite associations with diabetes were identified at a Bonferroni level of significance (p < 2.3 × 10(-5)), 16 of which have never been reported. Sixty-five of these diabetes-associated metabolites were associated with at least one marker of glycaemic control in the diabetes group. Using Gaussian graphical modelling, we constructed a metabolic network that links diabetes-associated metabolites from three biofluids across three different timescales of glycaemic control. CONCLUSIONS/INTERPRETATION: Our study reveals a complex network of biochemical dysregulation involving metabolites from different pathways of diabetes pathology, and provides a reference framework for future diabetes studies with metabolic endpoints. PMID: 26049400 [PubMed - as supplied by publisher]

Novel methodologies for biomarker discovery in atherosclerosis.

Sun, 07/06/2015 - 13:11
Novel methodologies for biomarker discovery in atherosclerosis. Eur Heart J. 2015 Jun 5; Authors: Hoefer IE, Steffens S, Ala-Korpela M, Bäck M, Badimon L, Bochaton-Piallat ML, Boulanger CM, Caligiuri G, Dimmeler S, Egido J, Evans PC, Guzik T, Kwak BR, Landmesser U, Mayr M, Monaco C, Pasterkamp G, Tuñón J, Weber C, ESC Working Group Atherosclerosis and Vascular Biology Abstract Identification of subjects at increased risk for cardiovascular events plays a central role in the worldwide efforts to improve prevention, prediction, diagnosis, and prognosis of cardiovascular disease and to decrease the related costs. Despite their high predictive value on population level, traditional risk factors fail to fully predict individual risk. This position paper provides a summary of current vascular biomarkers other than the traditional risk factors with a special focus on the emerging -omics technologies. The definition of biomarkers and the identification and use of classical biomarkers are introduced, and we discuss the limitations of current biomarkers such as high sensitivity C-reactive protein (hsCRP) or N-terminal pro-brain natriuretic peptide (NT-proBNP). This is complemented by circulating plasma biomarkers, including high-density lipoprotein (HDL), and the conceptual shift from HDL cholesterol levels to HDL composition/function for cardiovascular risk assessment. Novel sources for plasma-derived markers include microparticles, microvesicles, and exosomes and their use for current omics-based analytics. Measurement of circulating micro-RNAs, short RNA sequences regulating gene expression, has attracted major interest in the search for novel biomarkers. Also, mass spectrometry and nuclear magnetic resonance spectroscopy have become key complementary technologies in the search for new biomarkers, such as proteomic searches or identification and quantification of small metabolites including lipids (metabolomics and lipidomics). In particular, pro-inflammatory lipid metabolites have gained much interest in the cardiovascular field. Our consensus statement concludes on leads and needs in biomarker research for the near future to improve individual cardiovascular risk prediction. PMID: 26049157 [PubMed - as supplied by publisher]

Metabolomic profiles illuminate the efficacy of Chinese herbal Da-Cheng-Qi decoction on acute pancreatitis in rats.

Sun, 07/06/2015 - 13:11
Metabolomic profiles illuminate the efficacy of Chinese herbal Da-Cheng-Qi decoction on acute pancreatitis in rats. Pancreatology. 2015 May 11; Authors: Li J, Zhu SF, Zhao XL, Liu YX, Wan MH, Guo H, Liu YL, Gong HL, Chen GY, Tang WF Abstract BACKGROUND AND OBJECTIVES: Chinese herbal drug Da-Cheng-Qi decoction (DCQD) has been widely used for decades to treat acute pancreatitis (AP). Previous trials are mostly designed to state the potential mechanisms of the therapeutic effects rather than to detect its whole effect on metabolism. This study aimed to investigate the efficacy of DCQD on metabolism in AP. METHODS: Twenty-two male adult Sprague-Dawley rats were randomized into three groups. AP was induced by retrograde ductal infusion of 3.5% sodium taurocholate solution in DCQD and AP group, while 0.9% saline solution was used in sham operation (SO) group. Blood samples were obtained 12 h after drug administration and a 600 MHz superconducting Nuclear Magnetic Resonance (NMR) spectrometer was used to detected plasma metabolites. Principal Components Analysis (PCA) and Partial Least Squares-Discriminant Analysis after Orthogonal Signal Correction (OSC-PLS-DA) were applied to analyze the Longitudinal Eddy-delay (LED) and Carr-Purcell-Meiboom-Gill (CPMG) spectra. RESULTS: Differences in concentrations of metabolites among the three groups were detected by OSC-PLS-DA of 1HNMR spectra (both LED and CPMG). Compared with SO group, DCQD group had higher levels of plasma glycerol, glutamic acid, low density lipoprotein (LDL), saturated fatty acid (FA) and lower levels of alanine and glutamine, while the metabolic changes were reversed in the AP group. CONCLUSIONS: Our results demonstrated that DCQD was capable of altering the changed concentrations of metabolites in rats with AP and 1HNMR-based metabolomic approach provided a new methodological cue for systematically investigating the efficacies and mechanisms of DCQD in treating AP. PMID: 26048200 [PubMed - as supplied by publisher]

Metabolomic Endotype of Asthma.

Sun, 07/06/2015 - 13:11
Metabolomic Endotype of Asthma. J Immunol. 2015 Jun 5; Authors: Comhair SA, McDunn J, Bennett C, Fettig J, Erzurum SC, Kalhan SC Abstract Metabolomics, the quantification of small biochemicals in plasma and tissues, can provide insight into complex biochemical processes and enable the identification of biomarkers that may serve as therapeutic targets. We hypothesized that the plasma metabolome of asthma would reveal metabolic consequences of the specific immune and inflammatory responses unique to endotypes of asthma. The plasma metabolomic profiles of 20 asthmatic subjects and 10 healthy controls were examined using an untargeted global and focused metabolomic analysis. Individuals were classified based on clinical definitions of asthma severity or by levels of fraction of exhaled NO (FENO), a biomarker of airway inflammation. Of the 293 biochemicals identified in the plasma, 25 were significantly different among asthma and healthy controls (p < 0.05). Plasma levels of taurine, lathosterol, bile acids (taurocholate and glycodeoxycholate), nicotinamide, and adenosine-5-phosphate were significantly higher in asthmatics compared with healthy controls. Severe asthmatics had biochemical changes related to steroid and amino acid/protein metabolism. Asthmatics with high FENO, compared with those with low FENO, had higher levels of plasma branched-chain amino acids and bile acids. Asthmatics have a unique plasma metabolome that distinguishes them from healthy controls and points to activation of inflammatory and immune pathways. The severe asthmatic and high FENO asthmatic have unique endotypes that suggest changes in NO-associated taurine transport and bile acid metabolism. PMID: 26048149 [PubMed - as supplied by publisher]

Pavement cells: a model system for non-transcriptional auxin signalling and crosstalks.

Sun, 07/06/2015 - 13:11
Pavement cells: a model system for non-transcriptional auxin signalling and crosstalks. J Exp Bot. 2015 Jun 4; Authors: Chen J, Wang F, Zheng S, Xu T, Yang Z Abstract Auxin (indole acetic acid) is a multifunctional phytohormone controlling various developmental patterns, morphogenetic processes, and growth behaviours in plants. The transcription-based pathway activated by the nuclear TRANSPORT INHIBITOR RESISTANT 1/auxin-related F-box auxin receptors is well established, but the long-sought molecular mechanisms of non-transcriptional auxin signalling remained enigmatic until very recently. Along with the establishment of the Arabidopsis leaf epidermal pavement cell (PC) as an exciting and amenable model system in the past decade, we began to gain insight into non-transcriptional auxin signalling. The puzzle-piece shape of PCs forms from intercalated or interdigitated cell growth, requiring local intra- and inter-cellular coordination of lobe and indent formation. Precise coordination of this interdigitated pattern requires auxin and an extracellular auxin sensing system that activates plasma membrane-associated Rho GTPases from plants and subsequent downstream events regulating cytoskeletal reorganization and PIN polarization. Apart from auxin, mechanical stress and cytokinin have been shown to affect PC interdigitation, possibly by interacting with auxin signals. This review focuses upon signalling mechanisms for cell polarity formation in PCs, with an emphasis on non-transcriptional auxin signalling in polarized cell expansion and pattern formation and how different auxin pathways interplay with each other and with other signals. PMID: 26047974 [PubMed - as supplied by publisher]

Sulfur amino acid metabolism in Zucker diabetic fatty rats.

Sun, 07/06/2015 - 13:11
Sulfur amino acid metabolism in Zucker diabetic fatty rats. Biochem Pharmacol. 2015 Jun 3; Authors: Kwak HC, Kim YM, Oh SJ, Kim SK Abstract The present study was aimed to investigate the metabolomics of sulfur amino acids in Zucker diabetic fatty (ZDF) rats, an obese type 2 diabetic animal model. Plasma levels of total cysteine, homocysteine and methionine, but not glutathione (GSH) were markedly decreased in ZDF rats. Hepatic methionine, homocysteine, cysteine, betaine, taurine, spermidine and spermine were also decreased. There are no significant difference in hepatic S-adenosylmethionine, S-adenosylhomocysteine, GSH, GSH disulfide, hypotaurine and putrescine between control and ZDF rats. Hepatic SAH hydrolase, betaine-homocysteine methyltransferase and methylene tetrahydrofolate reductase were up-regulated while activities of gamma-glutamylcysteine ligase and methionine synthase were decreased. The area under the curve (AUC) of methionine and methionine-d4 was not significantly different in control and ZDF rats treated with a mixture of methionine (60mg/kg) and methionine-d4 (20mg/kg). Moreover, the AUC of the increase in plasma total homocysteine was comparable between two groups, although the homocysteine concentration curve was shifted leftward in ZDF rats, suggesting that the plasma total homocysteine after the methionine loading was rapidly increased and normalized in ZDF rats. These results show that the AUC of plasma homocysteine is not responsive to the up-regulation of hepatic BHMT in ZDF rats. The present study suggests that the decrease in hepatic methionine may be responsible for the decreases in its metabolites, such as homocysteine, cysteine, and taurine in liver and consequently decreased plasma homocysteine levels. PMID: 26047850 [PubMed - as supplied by publisher]

[Discrimination of common oral streptococcus with metabonomics method].

Sun, 07/06/2015 - 13:11
Related Articles [Discrimination of common oral streptococcus with metabonomics method]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2009 Oct;27(5):553-6 Authors: Guo Q, Xiao LY, Zhou XD, Li MY, Lu WX, Xiong P, Jia XM, Li W Abstract OBJECTIVE: To evaluate the feasibility of identifying oral streptococcus by comparing their metabolic profiling, and to find a convenient and rapid way to discriminate oral microorganisms. METHODS: The pure cultivation of Streptococcus sanguis ATCC 10556 and Streptococcus sobrinus 6715 (reference strain) from solid culture were respectively inoculated in TPY liquid medium. Then the growth quantity was measured periodically by turbidimetry and the growth curves of the inoculated bacteria were completed. The culture solutions in the stationary phase of the two bacteria were centrifuged, and then tested with the 1H-nuclear magnetic resonance (1H-NMR) spectrometer respectively. The gained free induction decay (FID) data were all inputted into MestReC Soft and finally transformed into metabolic profiling. The metabolic profiles were integrated segmentingly and the results were inputted into SIMCA-P Soft for principal components analysis (PCA). RESULTS: The PCA results showed the obvious clustering phenomena and the points of two group data differentially centralized in two clusters. Therefore, the NMR-based metabonomics profiles can discriminate the two different kinds of bacteria. CONCLUSION: The metabonomics can be expected to be a kind of promising useful method in quick discrimination of oral streptococcus. PMID: 19927732 [PubMed - indexed for MEDLINE]

[Preliminary study on the discrimination of putative periodontal pathogens with a metabonomics method].

Sun, 07/06/2015 - 13:11
Related Articles [Preliminary study on the discrimination of putative periodontal pathogens with a metabonomics method]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2009 Jun;27(3):310-2, 316 Authors: Lu WX, Wu YF, Xiao LY, Li MY, Guo Q, Xiong P, Jia XM, Xiao XR, Zhu Z, Gong QM, Li W Abstract OBJECTIVE: To evaluate the feasibility of identifying oral pathogenic bacteria by comparing the metabolic profiling of putative periodontal pathogens and try to find a convenient and rapid way to discriminate oral microorganisms. METHODS: Suspensions of Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum with same density were prepared and cultured respectively at liquid BHI medium. Then the growth quantity was measured periodically through turbidimetry and the growth curves of the inoculated bacteria were completed. The culture solutions of stable growth phase were sampled and characterized by 1H-nuclear magnetic resonance 1H-NMR). The data of 1H-NMR spectroscope results were analyzed by principal components analysis (PCA). RESULTS: The PCA showed the obvious clustering phenomena and the points of three groups differentially centralized to three clusters. Therefore, the NMR-based metabonomics profiles could discriminate the three different kinds of bacteria. CONCLUSION: The metabonomics is a potential classable method to identify the oral pathogenic bacteria. PMID: 19637485 [PubMed - indexed for MEDLINE]

[A preliminary investigation on plasma of non-syndromic cleft lip and/or palate using nuclear magnetic resonance-based metabonomics].

Sun, 07/06/2015 - 13:11
Related Articles [A preliminary investigation on plasma of non-syndromic cleft lip and/or palate using nuclear magnetic resonance-based metabonomics]. Hua Xi Kou Qiang Yi Xue Za Zhi. 2009 Apr;27(2):147-9, 153 Authors: Song JK, Zhou JL, Luo H, Shi B, Huang J, Li W Abstract OBJECTIVE: To access the feasibility of employing metabonomics method in clinical studies. This pilot study intends to introduce nuclear magnetic resonance (NMR)-based metabonomics method to elucidate the metabolism of non-syndromic cleft lip and/or palate (NSCLP) patients. METHODS: High-resolution 1H NMR spectroscopy was performed on blood plasma obtained from NSCLP and non-malformed children. All signal of 1H NMR spectra were recognized within MESTRE-v4.7, and the 1H NMR spectra integration into bins (or buckets) across the spectral regions of bin 0.04 was performed automatically in MESTRE-v4.7. The resulting data matrix was further analyzed, which was performed by SIMCA-P 11.0. The principal component analysis (PCA) was applied to the centered data to explore any clustering behavior of the samples. RESULTS: The results demonstrated the metabonomic difference in plasma between NSCLP and non-malformed children at least lies in 3-Hydroxybutyrate gamma-CH3, arginine and valine. Arginine excretion appeared to be higher in the non-malformed children population, while NSCLP population excreted higher concentrations of 3-Hydroxybutyrate gamma-CH3 and valine. CONCLUSION: The present study clearly demonstrated the great potential of the NMR-based metabonomics approach in elucidating the NSCLP plasma metabolism and the possibility of application in clinic diagnosis and screening. PMID: 19472875 [PubMed - indexed for MEDLINE]

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