BeerMIMS: Exploring the Use of Membrane-Inlet Mass Spectrometry (MIMS) Coupled to KNIME for the Characterization of Danish Beers

Beer is a complex mix of more than 7700 compounds, around 800 of which are volatile. While GC-MS has been actively employed in the analysis of the volatome of beer, this method is challenged by the complex nature of the sample. Herein, we explored the possible of using membrane-inlet mass spectrometry (MIMS) coupled to KNIME to characterize local Danish beers. KNIME stands for Konstanz Information Miner and is a free open-source data processing software which comes with several prebuilt nodes, that, when organized, result in data processing workflows allowing swift analysis of data with outputs that can be visualized in the desired format. KNIME has been shown to be promising in automation of large datasets and requires very little computing power. In fact, most of the computations can be carried out on a regular PC. Herein, we have utilized a KNIME workflow for data visualization of MIMS data to understand the global volatome of beers. Feature identification was not possible as of now but with a combination of MIMS and a KNIME workflow, we were able to distinguish beers from different micro-breweries located in Denmark, laying the foundation for the use of MIMS in future analysis of the beer volatome.

Evaluation of an integrative Bayesian peptide detection approach on a combinatorial peptide library

Detection of peptides lies at the core of bottom-up proteomics analyses. We examined a Bayesian approach to peptide detection, integrating match-based models (fragments, retention time, isotopic distribution, and precursor mass) and peptide prior probability models under a unified probabilistic framework. To assess the relevance of these models and their various combinations, we employed a complete- and a tail-complete search of a low-precursor-mass synthetic peptide library based on oncogenic KRAS peptides. The fragment match was by far the most informative match-based model, while the retention time match was the only remaining such model with an appreciable impact––increasing correct detections by around 8 %. A peptide prior probability model built from a reference proteome greatly improved the detection over a uniform prior, essentially transforming de novo sequencing into a reference-guided search. The knowledge of a correct sequence tag in advance to peptide-spectrum matching had only a moderate impact on peptide detection unless the tag was long and of high certainty. The approach also derived more precise error rates on the analyzed combinatorial peptide library than those estimated using PeptideProphet and Percolator, showing its potential applicability for the detection of homologous peptides. Although the approach requires further computational developments for routine data analysis, it illustrates the value of peptide prior probabilities and presents a Bayesian approach for their incorporation into peptide detection.

Elucidating the Fragmentation Mechanism of Protonated Lewis A Trisaccharide using MSn CID

Lewis blood group antigens are a prominent example of isomeric oligosaccharides with biological activity. Understanding the fragmentation mechanism in the gas phase is essential for their identification and assignment by mass spectrometric methods such as ESI-MS. In this work, the [M + H]+ species of Lewis A trisaccharide and Lewis A trisaccharide methyl glycoside were studied by ESI-MS with FT-ICR as mass analyzer with respect to their fragmentation mechanism. The comparison between the underivatized and the methylated species has shown that the reducing end plays a key role in this mechanism. The results of this study question the existence of Z-type fragment ions after activation of the protonated species. The main product of the fragmentation are Y-type fragment ions and a combination of Y-type fragmentation and the loss of water at the reducing end instead of Z-type fragmentation. C-type fragment ions could not be detected. MS3 measurements also reveal that each fragment ion only occurs with the participation of a mobile proton and the possibility of glycosidic bond cleavage after fragmentation has already occurred at the reducing end as B2 fragment ion.

Development and validation of ultra performance liquid chromatography-tandem mass spectrometry method for the simultaneous estimation of dolutegravir, lamivudine and tenofovir in bulk and tablet dosage form

A simple, selective and rapid ultra performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous estimation of dolutegravir, lamivudine and tenofovir in bulk and tablet dosage form. Chromatographic separation was attained on Acquity Ethylene Bridged Hybrid (BEH) C18 column (50 × 2.1 mm, 3.5 µm), using a mixture of acetonitrile and 0.1% formic acid in water (60:40, v/v) as a mobile phase at a flow rate of 0.12 mL/min. The total run time of analysis was 3.5 min. The analytes were detected using tandem mass spectrometry, operating in positive ionization and multiple reaction monitoring modes. The method's linearity was determined to be in the range of 10–150 ng/mL with r2 > 0.99. The proposed method was validated as per the International Council for Harmonization (ICH) guidelines, and the results were found well within the acceptance limits. The method was successfully applied for the simultaneous quantification of all the three analytes in the combined tablet dosage form.

Discovery of metabolomic biomarkers for discriminating platinum-sensitive and platinum-resistant ovarian cancer by using GC-MS

This study aims to determine ovarian cancer (OC) patients with platinum resistance for alternative treatment protocols by using metabolomic methodologies. Urine and serum samples of platinum-resistant and platinum-sensitive OC were analyzed using GC-MS. After data processing of GC-MS raw data, multivariate analyses were performed to interpret complex data for biologically meaningful information and to identify the biomarkers that cause differences between two groups. The biomarkers were verified after univariate, multivariate, and ROC analysis. Finally, metabolomic pathways related to group separations were specified. The results of biomarker analysis showed that 3,4-dihydroxyphenylacetic acid, 4-hydroxybutyric acid, L-threonine, D- mannose, and sorbitol metabolites were potential biomarkers in urine samples. In serum samples, L-arginine, linoleic acid, L-glutamine, and hypoxanthine were identified as important biomarkers. R2Y, Q2, AUC, sensitivity and specificity values of platinum-resistant and sensitive OC patients’ urine and serum samples were 0.85, 0.545, 0.844, 91.30%, 81.08 and 0.570, 0.206, 0.743, 77.78%, 74.28%, respectively. In metabolic pathway analysis of urine samples, tyrosine metabolism and fructose and mannose metabolism were found to be statistically significant (p < 0.05) for the discrimination of the two groups. While 3,4-dihydroxyphenylacetic acid, L-tyrosine, and fumaric acid metabolites were effective in tyrosine metabolism. D-sorbitol and D-mannose metabolites were significantly important in fructose and mannose metabolism. However, seven metabolomic pathways were significant (p < 0.05) in serum samples. In terms of p-value, L-glutamine in the nitrogen metabolic pathway from the first three pathways; L-glutamine and pyroglutamic acid metabolites in D-glutamine and D-glutamate metabolism. In the arginine and proline metabolic pathway, L-arginine, L-proline, and L-ornithine metabolites differed significantly between the two groups.

Theoretical description of electric fields in three-dimensional multipole ion traps

In this paper, the principle of forming the spatial distribution of the potential in multipole three-dimensional ion traps of a general type is considered. A matrix method for describing the electric fields in ion traps for the [Formula: see text]th order of multipole is proposed. Typical electrode geometries for hexapole and octupole traps are considered.

Joseph John Thomson investigates the paranormal

Joseph John Thomson is best known for detecting two isotopes of neon within cathode ray tubes that lay the foundation of the field of mass spectrometry. He was awarded the 1906 Nobel Prize in Physics for the discovery of the electron and for his work on the conduction of electricity in gases in the same devices. He is less known for his strong religious beliefs and his interest in psychical research and the paranormal. Thomson served as a member of the Society for Psychical Research for over 50 years and even became its Vice President. During this time, he attended a number of séances and demonstrations by professed psychics and mediums. This article traces those who influenced his interest in the paranormal, from Balfour Stewart to Lord Rayleigh and William Crookes. It reports and illustrates his beliefs and experiences investigating the paranormal in his own words.

Vacuum ultraviolet photoionization and dissociative photoionization of toluene: Experimental and theoretical insights

The photoionization and dissociative photoionization of toluene have been studied using synchrotron radiation vacuum ultraviolet light with photon energy in the range of 8.50–25.50 eV. The ionization energies (8.82 eV) and double ionization energies (23.80 eV) of toluene as well as the appearance energies for its major fragments C7H7+ (11.17/10.71 eV), C6H5+ (13.73 eV), C5H6+ (13.58/12.50 eV), C5H5+ (16.23 eV), C4H5+ (15.64 eV), C4H4+ (16.10 eV) and C4H3+ (17.11 eV) are determined, respectively by using photoionization efficiency spectrometry. With the help of experimental and theoretical results, seven dissociative photoionization channels have been proposed: C7H7+ + H, C6H5+ + CH3, C5H6+ + C2H2, C5H5+ + C2H2 + H, C4H5+ + C3H3, C4H4+ + C3H4 and C4H3+ + C3H4 + H. In addition, the geometries of the intermediates, transition states and products involved in these photoionization and dissociative photoionization processes have been performed at the B3LYP/6-311++G(d, p) level. The mechanisms of dissociative photoionization of toluene and the intermediates and transition states involved are discussed in detail. Generally speaking, the experimental results are in agreement with theoretical calculations in this work and published literature results. Especially the mechanisms of dissociative photoionization to C4H5+, C4H4+ and C4H3+ were discussed for the first time in this work. This investigation may provide useful information on understanding the photoionization and dissociative photoionization of toluene.

Proximity Effects in Mass Spectra of Benzanilides

The analytical value of peaks arising by a proximity effect in the electron ionization mass spectra of benzanilides has been established by examining the spectra of numerous examples of general structure XC6H4NHCOC6H4Y. Significant [M-X]+ signals are observed only when X = Cl, Br, I or CH3O in the 2-position. The presence of strong [M-X]+ signals, but negligibly weak [M-Y]+ peaks, even when the C-Y bond would be expected to break more readily than the C-X bond, indicates that these diagnostically useful signals do not arise by simple cleavage. Similarly, the presence of an appreciable [M-Cl]+ signal, but no [M-Br]+ signal, in the spectra of representative examples of 4-Br-2ClC6H3NHCOC6H4Y, reveals that loss of a substituent from the 2-position occurs much more rapidly than fission of a weaker bond to a substituent in the 4-position. These trends are interpreted in terms of cyclization of the ionized 2-substituted benzanilide, followed by elimination of the substituent originally in the 2-position, to form a protonated 2-arylbenzoxazole.

High-resolution mass spectrometry reveals a complex ganglioside pattern and novel polysialylated structures associated with the human motor cortex

We have developed here a superior methodology based on high-resolution mass spectrometry for screening and fragmentation analysis of gangliosides extracted and purified from the human motor cortex . The experiments, conducted on a nanoelectrospray Orbitrap mass spectroscope in the negative ion mode, allowed the discrimination in the native mixture extracted from human motor cortex of no less than 83 different gangliosides, which represents the highest number of structures identified so far in this brain region. The spectral data, acquired in high-resolution mass spectrometry mode with a remarkable sensitivity and an average mass accuracy of 4.48 ppm, also show that the gangliosidome of motor cortex is generally characterized by species exhibiting a much higher degree of sialylation than previously known. Motor cortex was found dominated by complex structures with a sialylation degree ≥3, exhibiting long saccharide chains, in the G1 class. Fucogangliosides and species with the glycan chain elongated by either O-acetylation and/or acetate anion attachments were also detected; the later modification was for the first time discovered in this brain region. Of major significance is the identification of hepta and octasialylated species of GS1 and GO1 type, which are among the structures with the longest oligosaccharide chain discovered so far in the human brain. In the last stage of research, tandem mass spectrometry performed by higher energy collision dissociation provided structural data documenting the occurrence of GT1b (d18:1/20:0) isomer in the human motor cortex.