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Two-dimensional (2D) (Super 59)Co correlation spectroscopy (COSY)/Double-quantum-filtered (DQF)COSY experiments are reported for three tetrahedral mixed-metal clusters HFeCo3(CO)11L with L = PPh3, p(OMe)3, and PCy3 (Cy = cyclohexyl). The 2-D (Super 59)Co COSY and DQFCOSY NMR spectra of these clusters in solution prove the existence of a scalar coupling constant between the (super 59)Co nuclei.

Research is presented concerning the use of high-resolution magic angle spinning NMR spectroscopy to determine the structure of the 141-159 sequence of the foot-and-mouth disease virus capsid viral protein VP1.

Abstract Introduction Providing information on cancerous tissue samples during a surgical operation can help surgeons delineate the limits of a tumoral invasion more reliably. Here, we describe the use of metabolic profiling of a colon biopsy specimen by high resolution magic angle spinning nuclear magnetic resonance spectroscopy to evaluate tumoral invasion during a simulated surgical operation. Case presentation Biopsy specimens (n = 9) originating from the excised right colon of a 66-year-old Caucasian women with an adenocarcinoma were automatically analyzed using a previously built statistical model. Conclusions Metabolic profiling results were in full agreement with those of a histopathological analysis. The time-response of the technique is sufficiently fast for it to be used effectively during a real operation (17 min/sample). Metabolic profiling has the potential to become a method to rapidly characterize cancerous biopsies in the operation theater.

Background: High‐resolution magic angle spinning (HRMAS) is a nuclear magnetic resonance (NMR) technique that enables the characterization of metabolic phenotypes/metabolite profiles of cells, tissues, and organs, under both normal and pathological conditions, without resorting to time‐consuming extraction techniques. Objectives: To assess the impact of chemical skin sensitizers vs non‐sensitizers on the metabolome of three‐dimensional reconstructed human epidermis (RHE) by HRMAS NMR. Methods: Based on the SENS‐IS assay, 12 skin sensitizers and five non‐sensitizing chemicals were investigated and applied on EpiSkin RHE at the published maximal non‐irritating concentrations under the conditions of the test. The metabolome of RHE samples was then analyzed by HRMAS NMR. Results: A total of 32 different metabolites were identified; 20 of these were quantified for all samples. Statistical univariate analysis showed that the tissue content of most measured metabolites (with the exception of acetate and glucose) was different in the untreated, treated with non‐sensitizers, and treated with sensitizers samples. In RHE samples in contact with sensitizing chemicals, concentrations of 18 metabolites were significantly decreased. Alanine and tyrosine could not discriminate between sensitizer‐ and non‐sensitizer‐treated groups. A multivariate partial least‐squares‐discriminant analysis was performed on the two treated groups, discriminating sensitizing and non‐sensitizing chemicals with a very good R2Y value of 0.87 and a good Q2Y value of 0.70. Conclusions: Data suggest that HRMAS NMR could be used to monitor the impact of chemicals, skin allergens vs non‐sensitizers, on the metabolome of three‐dimensional RHE. Highlights: A total of 32 different metabolites were identified in reconstructed human epidermis (RHE) by high‐resolution magic angle spinning nuclear magnetic resonance, among which 20 could be quantified for all samples.Statistical univariate analysis showed that the measured metabolites were different in the RHE samples treated with sensitizers vs non‐sensitizers.A multivariate partial least‐squares‐discriminant analysis was performed on the two treated groups, discriminating sensitizing and non‐sensitizing chemicals. [ABSTRACT FROM AUTHOR]

The specific metabolic profile of aqueous extracts of caviar samples ( n = 91) originating from producers in the Aquitaine region in France was determined using H NMR spectroscopy. This metabolic profile was used to develop multivariate statistical models (Soft Independent Modeling by Class Analogy (SIMCA) and Orthogonal Partial Least Square Discriminant Analysis (OPLS-DA)) for the purpose of differentiating the Aquitaine production from other productions. The main purpose of these models is to help Aquitaine producers establish a protected geographical indication (PGI) to protect their know-how in caviar production from aquaculture. The parameters characterizing both the OPLS-DA and the SIMCA models were quite satisfactory, and the analysis of blind test samples with the two models provided a good level of discrimination between Aquitaine caviars and other caviars. The same NMR metabolic profile could also be used to provide an estimation of the freshness of caviar samples and define a shelf life for caviar cans. The first characterization of the different metabolites detected in caviar specimens by H NMR spectroscopy is also presented. The statistical models obtained could be used to prevent counterfeiting of Aquitaine caviar and guarantee an adequate level of freshness. [ABSTRACT FROM AUTHOR]

Paragangliomas (PGLs) are frequently associated with germline mutations in genes involved in energy metabolism. The purpose of the present study was to assess whether the tumor metabolomic profile of patients with hereditary and apparently sporadic PGLs enables the distinction of different subtypes of tumors. Twenty-eight unrelated patients with a histological diagnosis of PGLs were included in the present study. Twelve had germline mutations in SDHx genes (5 SDHB, 7 SDHD), 6 VHL, and 10 were apparently sporadic. Intact tumor samples from these patients (one per patient) were evaluated with 1H high-resolution magic angle spinning (HRMAS) NMR spectroscopy. SDHx-related tumors were characterized by an increase in succinate levels in comparison to other tumor subtypes (p = 0.0001 vs VHL and p = 0.000003 vs apparently sporadic). Furthermore, we found significantly lower values of glutamate in SDHx-related tumors compared to other subtypes (p = 0.0007 vs VHL and p = 0.003 vs apparently sporadic). Moreover, SDHx-tumors also exhibited lower values of ATP/ADP/AMP (p = 0.01) compared to VHL. VHL tumors were found to have the highest values of glutathione (GSH) compared to other tumors. Based on 4 metabolites (succinate, glutamate, GSH, and ATP/ADP/AMP), tumors were accurately distinguished from the other ones on both 3- and 2-class PLS-DA models. The present study shows that HRMAS NMR spectroscopy is a very promising method for investigating the metabolomic profile of various PGLs. The present data suggest the existence of a specific succinate-glutamate hallmark of SDHx PGLs. The relevance of such a metabolomic hallmark is expected to be very useful in designing novel treatment options as well as improving the diagnosis and follow-up of these tumors, including metastatic ones. [ABSTRACT FROM AUTHOR]

In this study, we i assessed the metabolic profile of the normal adrenal cortex and medulla of adult human subjects by means of ¹H-high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) spectroscopy; ii) compared the biochemical profile of adenoma (Ad), adrenal cortical carcinoma (ACC), and pheochromocytoma (PCC) samples with that of healthy adrenal tissue samples; and iii) investigated the metabolic differences between ACCs and Ads as well as between ACCs and PCCs. Sixty-six tissue samples (13 adrenal cortical tissue, eight medullary tissue, 13 Ad, 12 ACC, and 20 PCC samples) were analyzed. Adrenaline and noradrenaline were undetectable in cortical samples representing the metabolic signature of the tissue derived from neural crest. Similarity between the metabolic profile of Ads and that of the normal adrenal cortex was shown. Inversely, ACC samples clearly made up a detached group exhibiting the typical stigmata of neoplastic tissue such as choline-containing compounds, biochemical markers of anaerobic processes, and increased glycolysis. Significantly higher levels of lactate, acetate, and total choline-containing compounds played a major role in the differentiation of ACCs from Ads. Moreover, the high fatty acid content of ACCs contributed to the cluster identification of ACCs. Of the 14 sporadic PCC samples, 12 exhibited predominant or exclusive noradrenaline secretion. The noradrenaline: adrenaline ratio was inverted in the normal medullary tissue samples. Multiple endocrine neoplasia type 2- and NF1-related PCC samples exhibited both adrenaline and noradrenaline secretion. In the von Hippel-Lindau disease-related PCC samples, only noradrenaline secretion was detected by HRMASNMRspectroscopy. This study is one of the first applications of metabolomics to adrenal pathophysiology and it is the largest study to report HRMASNMR data related to the adrenal cortex and adrenal cortical tumors. [ABSTRACT FROM AUTHOR]

Standards are needed to control the quality of the lungs from nonheart-beating donors as potential grafts. This was here assessed using the metabolomics 1H high-resolution magic angle spinning NMR spectroscopy. Selective perfusion of the porcine bilung block was set up 30 min after cardiac arrest with cold Perfadex®. Lung alterations were analyzed at 3, 6, and 8 h of cold ischemia as compared to baseline and to nonperfused lung. Metabolomics analysis of lung biopsies allowed identification of 35 metabolites. Levels of the majority of the metabolites increased over time at 4°C without perfusion, indicating cellular degradation, whereas levels of glutathione decreased. When lung was perfused at 4°C, levels of the majority of the metabolites remained stable, including levels of glutathione. Levels of uracil by contrast showed a reverse profile, as its signal increased over time in the absence of perfusion while being totally absent in perfused samples. Our results showed glutathione and uracil as potential biomarkers for the quality of the lung. The metabolomics 1H high-resolution magic angle spinning NMR spectroscopy can be efficiently applied for the assessment of the quality of the lung as an original technique characterized by a rapid assessment of intact biopsy samples without extraction and can be implemented in hospital environment. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Two-dimensional (2D) 59Co correlation spectroscopy (COSY)/double-quantum-filtered (DQF)COSY experiments are reported for three tetrahedral mixed-metal clusters HFeCo3(CO)11L with L = PPh3, P(OMe)3, and PCy3 (Cy = cyclohexyl) in which the L-substituted Co center is chemically different from the other two. The 2D 59Co COSY and DQFCOSY NMR spectra of these clusters in solution prove the existence of a scalar coupling constant between the 59Co nuclei. To determine this value for each cluster, 2D 59Co COSY and DQFCOSY NMR spectra have been simulated by numerical density-matrix calculations. The predicted spectra mimic well the features of the experimental spectra if a scalar coupling is introduced between the Co nuclei. It was initially observed that the scalar coupling constants between the Co nuclei obtained from the 2D COSY and DQFCOSY NMR spectra differed significantly. In contrast to the 2D COSY spectra, the diagonal and cross peaks are of comparable intensity in the 2D DQFCOSY spectra, which leads to a considerable increase in the accuracy of the determination of the scalar coupling constant. [ABSTRACT FROM AUTHOR]

NMR spectra of ubiquitin in the presence of bicelles at a concentration of 32% w/v have been recorded at 700 MHz under sample spinning conditions at the magic angle (54.7°) and at an angle of 45.5°. At the magic angle, the 1H–15N HSQC spectrum of ubiquitin in bicelles is virtually indistinguishable from the one recorded on the protein in solution. Spinning the sample at the magic angle creates an isotropic environment with no preferred bicelle orientations, thus allowing the determination of scalar coupling constants. For an angle of rotation of 45.5°, the bicelles orient with their normal perpendicular to the spinning axis leading to the observation of strong residual dipolar couplings and chemical shift variations of the 15N resonances. [ABSTRACT FROM AUTHOR]