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The intensive investigation of chemical components from the culture broth of the bacterium Saccharomonospora sp. CNQ-490 has yielded four new natural products, lodopyridones D − G (1 − 4) along with the previously reported compounds, lodopyridones A − C (5 − 7) and cotteslosin A (8). The planar structures of the lodopyridones D − G (1 − 4) were elucidated by interpreting the mass spectrometry, ultraviolet (UV) spectroscopy, and 1D and 2D nuclear magnetic spectroscopy (NMR) data, as well as comparing NMR data with those of the lodopyridones A − C (5 − 7). [ABSTRACT FROM AUTHOR]

Nitrofurazone usage in food‐producing animals is prohibited in most countries, including the United States. Regulatory agencies regularly monitor its use in domestic, export/import animals' food products by measuring the semicarbazide (SEM) metabolite as a biomarker of nitrofurazone exposure. However, the use of SEM is controversial because it is also produced in food naturally and thus gives false positive results. A cyano‐metabolite, 4‐cyano‐2‐oxobutyraldehyde semicarbazone (COBS), is proposed as an alternate specific marker of nitrofurazone to distinguish nitrofurazone from treated or untreated animals. A synthetic method was developed to produce COBS via metallic hydrogenation of nitrofurazone. The product was isolated and characterized by one‐ and two‐dimensional nuclear magnetic spectroscopy (NMR) experiments, Fourier‐transform infrared spectroscopy (FT‐IR), and mass spectrometry. The developed synthetic procedure was further extended to synthesize isotopically labeled 4‐[13C]‐cyano‐2‐oxo‐ [2, 3, 4‐13C3]‐butyraldehyde semicarbazone. Labeled COBS is useful as an internal standard for its quantification in food‐producing animals. Thus, the developed method provides a possibility for its commercial synthesis to procure COBS. This is the first synthesis of the alternate specific marker metabolite of nitrofurazone for possible usage in regulatory analysis to solve a real‐world problem. [ABSTRACT FROM AUTHOR]

The atomic masses of isotopes of elements beyond fermium, which can presently only be produced online via fusion-evaporation reactions, have until recently been determined only from α decay chains reaching nuclides with known atomic masses. Especially in the case of lower-yield nuclides, for which the sufficiently detailed nuclear spectroscopy required to fully determine the nuclear structure is not possible, such indirect mass determinations may suffer systematic errors. For many superheavy nuclides, their decay chains end in spontaneous fission or in β -decay prior to reaching nuclides of known mass. To address this dearth of accurate atomic masses, we have developed a multi-reflection time-of-flight mass spectrograph that can make use of decay-correlations to accurately and precisely determine atomic masses for the very low-yield superheavy nuclides. [ABSTRACT FROM AUTHOR]

Introduction: The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized. Objectives: Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection. Methods: Cord blood plasma samples from 23 mild COVID-19 cases (mother infected/newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and liquid chromatography coupled with mass spectrometry. Metabolite set enrichment analysis (MSEA) was used to evaluate altered biochemical pathways due to COVID-19 intrauterine exposure. Logistic regression models were developed using metabolites to predict intrauterine exposure. Results: Significant concentration differences between groups (p-value < 0.05) were observed in 19 metabolites. Elevated levels of glucocorticoids, pyruvate, lactate, purine metabolites, phenylalanine, and branched-chain amino acids of valine and isoleucine were discovered in cases while ceramide subclasses were decreased. The top metabolite model including cortisol and ceramide (d18:1/23:0) achieved an Area under the Receiver Operating Characteristics curve (95% CI) = 0.841 (0.725–0.957) for detecting fetal exposure to maternal COVID-19 infection. MSEA highlighted steroidogenesis, pyruvate metabolism, gluconeogenesis, and the Warburg effect as the major perturbed metabolic pathways (p-value < 0.05). These changes indicate fetal increased oxidative metabolism, hyperinsulinemia, and inflammatory response. Conclusion: We present fetal biochemical changes related to intrauterine inflammation and altered energy metabolism in cases of mild maternal COVID-19 infection despite the absence of viral infection. Elucidation of the long-term consequences of these findings is imperative considering the large number of exposures in the population. [ABSTRACT FROM AUTHOR]

The overuse and misuse of marketed antimicrobial agents developed drug resistance, which has become a significant problem worldwide. A series of new coumarinyl-oxadiazole Schiff base derivatives were designed and synthesized. These synthesized molecules synthesis of coumarinyl-oxadiazole schiff base derivatives (FP1-FP7) were characterized using Infrared spectroscopy, proton nuclear magnetic spectroscopy, and mass spectroscopy and evaluated for their antibacterial potential against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Bacillus subtilis, Staphylococcus aureus) bacterial strain by measuring minimum inhibitory concentration values. Among the synthesized compounds, FP6 was found to be the best antibacterial agent having concentration values of 3.12 and 6.25 µg/ml against Gramnegative and Gram-positive bacteria, respectively. Compounds FP1-FP7 binding interaction with receptor Staph Gyrase B 24 kDa (PDB code: 4URM) were also studied, and docking score was in the range of -5.18 to -3.87 kcal/mol. Compounds FP6 and FP5 showed the best interaction with docking scores 5.18 and -5.17 kcal/mol, respectively. The antibacterial result showed satisfying structure-activity, which indicates that the electron density of coumarinyl-oxadiazole moiety highly influenced the antibacterial potential. Furthermore, the binding affinity with Staph Gyrase B 24kDa during molecular docking promotes synthetic research work. Hence, coumarinyl oxadiazole Schiff base derivatives could be a satisfying lead molecule as an antimicrobial agent. [ABSTRACT FROM AUTHOR]

A study of the spatial occurrence of iron precipitation in a high performance multicrystalline silicon (HPMC-Si) sample is presented. The separated effects of grain-boundaries, sparse intragranular dislocations, and dislocation clusters are investigated by combining the Fei imaging method with glow discharge mass spectroscopy, electron backscatter diffraction, and two iron precipitation models. While the area-averaged precipitation at grain boundaries is relatively minor, almost the whole iron precipitation occurs within the grains, despite the very low intra-granular dislocation density. The fraction of non-precipitated iron in the studied HPMC-Si material was found to be one to two orders of magnitude higher than that reported previously for standard materials. [ABSTRACT FROM AUTHOR]

Paramecium bursaria chlorella virus MA-1D is a chlorovirus that infects Chlorella variabilis strain NC64A, a symbiont of the protozoan Paramecium bursaria. MA-1D has a 339-kb genome encoding ca. 366 proteins and 11 tRNAs. Like other chloroviruses, its major capsid protein (MCP) is decorated with N -glycans, whose structures have been solved in this work by using nuclear magnetic spectroscopy and matrix-assisted laser desorption ionization-time of flight mass spectrometry along with MS/MS experiments. This analysis identified three N-linked oligosaccharides that differ in the nonstoichiometric presence of three monosaccharides, with the largest oligosaccharide composed of eight residues organized in a highly branched fashion. The N -glycans described here share several features with those of the other chloroviruses except that they lack a distal xylose unit that was believed to be part of a conserved core region for all the chloroviruses. Examination of the MA-1D genome detected a gene with strong homology to the putative xylosyltransferase in the reference chlorovirus PBCV-1 and in virus NY-2A, albeit mutated with a premature stop codon. This discovery means that we need to reconsider the essential features of the common core glycan region in the chloroviruses. [ABSTRACT FROM AUTHOR]

An etching process for SiO2 that employs atmospheric-pressure pulsed remote plasma with a mixture gas (CF4/Ar) has been demonstrated. The etch rate increased by increasing the pulse frequency and also increased rapidly with the addition of a small amount of O2 gas. A SiO2 etch rate of 400 nm/min was obtained without any bias supplied to the substrate, and more than 8 μm/min was obtained with H2O addition. The exhaust gas from the plasma source was investigated using ion attachment mass spectrometry (IAMS). With IAMS, the polymerized species were measured without the generation of fragment ions. The results suggest that HF molecules are generated by H2O addition to CF4 and that the etch rate of SiO2 depends on the density of HF molecules. [ABSTRACT FROM AUTHOR]

This paper reports on a systematic investigation of nitrogen (N) doping in single-crystalline TiO2 films possessing an anatase phase. TiO2 films heavily doped with N were grown with high crystallinity by employing a pulsed laser ablation technique using a close lattice-matched LaAlO3 (100) substrate and NO as the source gases for N doping. 15N and 18O isotope tracing by secondary-ion-mass spectroscopy confirmed that N and O atoms were simultaneously incorporated into the films as a consequence of the gas phase reactions between Ti-related chemical species ablated by the laser and NO free radicals. The films yielded an absorption band at around 3.0 eV, as expected from the yellowish color, with band tailing becoming stronger with increasing N concentration. It is suggested that N-related complex defects in TiO2 acted as carrier compensation centers. Micro-Raman spectroscopy with a spatial resolution of 1 μm2 revealed host-lattice defects and generation of secondary phases at the microscopic scale by N doping. This work showed that the visible absorption band in N-doped TiO2 films can be attributed to small structural modifications consisting of N-related complex defects and secondary phases formed at the microscopic scale. These structural modifications were associated with a concomitant enhancement in photocatalytic activity. [ABSTRACT FROM AUTHOR]

A sample of nitrogen-doped, single crystal Czochralski silicon was subjected to several different surface preparations. Secondary ion mass spectrometry depth profiling has shown that prolonged glancing-angle bombardment by 3–5 kV Ar+ ions significantly increases the nitrogen concentration in the near surface by up to an order of magnitude over the bulk value. Concentrations are observed to be elevated over the bulk value to a depth up to 25 μm. Nitrogen-implanted samples and samples with a 1 nm surface nitride did not exhibit nitrogen segregation under the same conditions, but a sample with 100 nm of surface nitride did exhibit ion bombardment induced drive-in. In nitride-free samples, the source of the nitrogen is indicated to be a nitrogen-rich layer in the first micron of material. The diffusion behavior of nitrogen in silicon is discussed and the Crowdion mechanism for diffusion is suggested as the enabling mechanism for the enhanced low temperature diffusion. [ABSTRACT FROM AUTHOR]

Tetra-nitrogen (N4), which has been the subject of recent controversy [Cacace, d. Petris, and Troiani, Science 295, 480 (2002); Cacace, Chem. Eur. J. 8, 3839 (2002); Nguyen et al., J. Phys. Chem. A 107, 5452 (2003); Nguyen, Coord. Chem. Rev. 244, 93 (2003)] as well as of great theoretical interest, has been prepared from the N4 +· cation and then detected as a reionized gaseous metastable molecule with a lifetime exceeding 0.8 μs in experiments based on neutralization-reionization mass spectrometry. Moreover, we have used the nature of the charge-transfer reaction which occurs between a beam of fast N4 +· ions (8 keV translational energy) and various stationary gas targets to identify the vertical neutralization energy of the N4 +· ion. The measured value, 10.3±0.5, most closely matches that of the lowest energy azidonitrene 4N4 +· Cs(4A′) ion, resulting in the formation of the neutral bound azidonitrene 3N4Cs(3A″). Neutralization of the global minimum 2N4 +· D ∞h (2∑u +) ion leads to a structure 166 kJ mol-1 above the dissociation products [N2(1∑g +) + N2(1∑g +)]; moreover, it was not possible to find a minimum on the 1N4 neutral potential energy surface for a covalently bonded structure. Ab initio calculations at the G3, QCISD/6-31G(d), and MP2/AUG-cc-pVTZ levels of theory have been used to determine geometries and both vertical neutralization energies of ions (doublet and quartet) and ionization energies of neutrals (singlet and triplet). In addition, we have also described in detail the EI ion source for the Ottawa VG ZAB mass spectrometer [Holmes and Mayer, J. Phys. Chem. A 99, 1366 (1995)] which was modified for high-pressure use, i.e., for the production of dimer and higher number cluster ions. [ABSTRACT FROM AUTHOR]

Mass spectrometry has been used to study the influence of the plasma chamber walls on the recombination rates of halogen atoms in a high density HBr/Cl[sub 2]/O[sub 2]/CF[sub 4] plasma used for silicon gate etching. In these plasmas, CF[sub 4] addition results in a transition from SiO[sub x] to CF[sub x] layer deposition on the chamber walls. We show that this is accompanied by an important enhancement of the surface recombination rate of halogen atoms (specially Br), whose gas phase concentration consequently drops. The same phenomenon is observed when photoresist is etched in an HBr/Cl[sub 2]/O[sub 2] plasma resulting in carbon coating of the chamber walls. This demonstrates that the recombination coefficient of Br atoms on organic polymer surfaces is much larger than on SiO[sub 2]-like surfaces, and that significant consequences on gate etch processes are expected. © 2003 American Institute of Physics. [ABSTRACT FROM AUTHOR]

MALDI-TOF mass spectrometry (MS) may be used as a rapid typing method for nosocomial pathogens. Here, we evaluated MALDI-TOF MS for discrimination of hospital outbreak-related clusters of Serratia marcescens and carbapenemase-producing Citrobacter freundii. Thirty-three S. marcescens isolates collected from neonatal intensive care unit (NICU) patients, and 23 C. freundii isolates including VIM-positive isolates from a hospital colonization outbreak were measured by Vitek MS. Consensus spectra of each isolate were clustered using SARAMIS software. Genotyping was performed by whole-genome sequencing (WGS). First, a set of 21 S. marcescens isolates from 2014 with seven genotypes including three monoclonal clusters was used for the evaluation of MALDI-TOF typing. MS clustering was largely in agreement with genotyping results when the similarity cut-off for clonal identity was set on 90%. MALDI-TOF cluster analysis was then investigated for the surveillance of S. marcescens in the NICU in 2017 and demonstrated the introduction of new strains into the hospital and nosocomial transmissions. MS analysis of the C. freundii outbreak in 2016 revealed a monoclonal cluster of VIM-positive isolates and the separation of epidemiologically non-related VIM-positive and negative isolates. Two additional VIM-positive Citrobacter isolates from food samples were closely related to the large monoclonal cluster. WGS confirmed the MS results. MALDI-TOF MS may be used as a first-line typing tool for S. marcescens and C. freundii to detect transmission events in the hospital because isolates of an identical WGS type were grouped into the same MS cluster. [ABSTRACT FROM AUTHOR]

Abstract The prospect of developing new bio-based products from lignin partially depends on the development of effective analytical techniques to characterize the end products from lignin degradation experiments. To date, the most utilized mass spectrometric technique for characterizing lignin oligomers has been negative ion mass spectrometry. Positive ion mass spectrometry remains a relatively unexplored approach for lignin sequencing. Here we report on the sequencing of lignin oligomers using lithium cationization positive ion electrospray followed by higher-energy collisional dissociation (HCD) tandem mass spectrometry on a high-resolution accurate-mass Orbitrap mass spectrometer. Thirteen synthetic lignin model oligomers containing β-O-4 and 4-O-α linkages were analyzed and sequenced based on their HCD tandem mass spectrometry fragmentation patterns. Proposed sequence-specific fragmentation pathways are provided. The method presented in this study provides a potential application of lithium cationization tandem mass spectrometry for the analysis of lignin degradation products. Graphical abstract Image 1 Highlights • Lithium forms stable adducts with lignin oligomers generating cations for positive ion mass spectrometry. • Tandem mass spectrometry of lithium-lignin precursors produces lithiated fragment ions. • The monolignol sequence of an oligomer can be determined from the tandem mass spectrum. • Lithium cationization provides an alternative means of lignin oligomer ionization that retains sequencing features. [ABSTRACT FROM AUTHOR]

Metabolomics is a powerful approach for discovering biomarkers and for characterizing the biochemical consequences of genetic variation. While untargeted metabolite profiling can measure thousands of signals in a single experiment, many biologically meaningful signals cannot be readily identified as known metabolites nor compared across datasets, making it difficult to infer biology and to conduct well-powered meta-analyses across studies. To overcome these challenges, we developed a suite of computational methods, PAIRUP-MS, to match metabolite signals across mass spectrometry-based profiling datasets and to generate metabolic pathway annotations for these signals. To pair up signals measured in different datasets, where retention times (RT) are often not comparable or even available, we implemented an imputation-based approach that only requires mass-to-charge ratios (m/z). As validation, we treated each shared known metabolite as an unmatched signal and showed that PAIRUP-MS correctly matched 70–88% of these metabolites from among thousands of signals, equaling or outperforming a standard m/z- and RT-based approach. We performed further validation using genetic data: the most stringent set of matched signals and shared knowns showed comparable consistency of genetic associations across datasets. Next, we developed a pathway reconstitution method to annotate unknown signals using curated metabolic pathways containing known metabolites. We performed genetic validation for the generated annotations, showing that annotated signals associated with gene variants were more likely to be enriched for pathways functionally related to the genes compared to random expectation. Finally, we applied PAIRUP-MS to study associations between metabolites and genetic variants or body mass index (BMI) across multiple datasets, identifying up to ~6 times more significant signals and many more BMI-associated pathways compared to the standard practice of only analyzing known metabolites. These results demonstrate that PAIRUP-MS enables analysis of unknown signals in a robust, biologically meaningful manner and provides a path to more comprehensive, well-powered studies of untargeted metabolomics data. [ABSTRACT FROM AUTHOR]

Highlights • A quasi -MRM mode by UPLC-QTOF-MS/MS was proposed. • A strategy to select ion pair of each analyte for quasi -MRM mode was highlighted. • The proposed mode was practiced by quantifying multi-components of Moutan Cortex. • The superiority in specificity and sensitivity of the proposed mode was proved. Abstract In this study, a time segment scanning-based quasi -multiple reaction monitoring (quasi -MRM) mode was proposed to improve the quantitative performance of UPLC-QTOF-MS/MS. To achieve the quasi -MRM mode, a strategy to select the ion pair (precursor and product ions) of each analyte was adopted as follows. First, a stable and abundant ion by quadrupole was set as precursor ion in MS scan mode. Second, the fragment ions of the precursor ion formed via collision-induced dissociation were measured by time-of-flight (TOF) in MS/MS scan mode; a characteristic, stable and abundant fragment ion (or precursor ion in case of fragment ion unavailable) was designated as the product ion. Third, the detection specificity and sensitivity of the product ion by TOF were strengthened through time segment scanning over a narrowed mass scan range. The proposed quasi -MRM mode achieved simultaneous quantification of fifteen major components in Moutan Cortex, a widely used medicinal herb, as well as its sulfur-fumigated samples. The quasi -MRM mode was methodologically compared with the other two quantitative modes commonly used in the UPLC-PDA-QTOF-MS/MS apparatus, namely UPLC-PDA and extracted ion analysis. The results demonstrated that the quasi -MRM mode performed better in specificity, sensitivity and linearity. The quasi -MRM mode was further validated with regard to precision, accuracy and stability. The research deliverables indicate that the proposed mode improved the quantitative capability of UPLC-QTOF-MS/MS, and therefore could serve as a potential mode for QTOF-MS/MS-based quantification of herbal medicines. [ABSTRACT FROM AUTHOR]

Highlights • Laser ionization is a powerful tool for characterization of environmental samples. • High sensitivity (factor 1000 compared to GC–MS) and selectivity is possible. • 6-8 ring PAH patterns detected in four environmental certified reference materials. • Up to 37 PAH concentrations additionally to the certificate information are gained. • Concentrations for 13 NSO-PAC determined for all four CRM. Abstract Proceedings in environmental analytical chemistry of polycyclic aromatic hydrocarbons (PAH) in the past decades cover improvements in laboratory methods as well as new insights in the toxicology of single PAH compounds. A re-evaluation of the established list of 16 priority PAH published by the U. S. Environmental Protection Agency seems overdue. In this study we have applied PAH analysis by atmospheric pressure laser ionization – mass spectrometry (APLI-MS) to NIST 1941b, NIST 1649b, BAM CC013a and IRMM BCR 535 giving further references in addition to the certificates of analysis. Gas chromatography enables to distinguish between different alkylated PAH derivatives whereas liquid chromatography additionally allows detection of PAH tentatively with six or more aromatic rings on the level of chemical formula. For an optimal isomer-specific differentiation, LC-APLI-MS should be used in combination with fluorescence detection. Distribution patterns of 6 and 7-ring PAH are presented for urban dust, marine and harbor sediments and the soil sample. Additionally, a set of 14 nitrogen, sulfur and oxygen-containing polycyclic aromatic compounds were analyzed by APLI and quantified in all reference materials for the first time. [ABSTRACT FROM AUTHOR]

Immunoglobulins are biomolecules involved in defence against foreign substances. Flexibility is key to their functional properties in relation to antigen binding and receptor interactions. We have developed an integrative strategy combining ion mobility mass spectrometry (IM‐MS) with molecular modelling to study the conformational dynamics of human IgG antibodies. Predictive models of all four human IgG subclasses were assembled and their dynamics sampled in the transition from extended to collapsed state during IM‐MS. Our data imply that this collapse of IgG antibodies is related to their intrinsic structural features, including Fab arm flexibility, collapse towards the Fc region, and the length of their hinge regions. The workflow presented here provides an accurate structural representation in good agreement with the observed collision cross section for these flexible IgG molecules. These results have implications for studying other nonglobular flexible proteins. Not to be IgG‐nored: An integrative strategy combining ion mobility mass spectrometry (IM‐MS) with molecular modelling can be used to study the conformational dynamics of human IgG antibodies. Predictive models of all four human IgG subclasses were assembled and their dynamics sampled in the transition from extended to collapsed state during IM‐MS. The structural representation is in good agreement with the observed collision cross sections. [ABSTRACT FROM AUTHOR]

Abstract The high-throughput screening by flow injection coupled to high-resolution mass spectrometry (HTS-FIA-HRMS) is a powerful technique that enables the identification of several types of samples in a short period of time, either with qualitative or quantitative purposes. Sensory attributes of tobacco are affected by its chemical composition, and it is very important to quantify multi-analytes in a high-throughput methodology. HTS-FIA-HRMS coupled to multivariate analysis was used to create calibration models for 27 analytes, or group of compounds, of tobacco sensory interest. The models were validated by different approaches, including permutation test to avoid overfitting, evaluation of the equipment repeatability by control samples, reproducibility comparison of results from two different equipment and analysts, and with a blind test analysis. All tests demonstrated a good response to the proposed method. No statistical difference between the errors of both equipment was observed, with less than 7% error from the control samples, and a blind test error between 5.96% and 20.10%. The partial least squares (O-PLS) regression models were applied to 815 samples, and a principal component analysis (PCA) was performed from the predicted concentration values, aiming at the non-supervised classification based on tobacco type. We expect that this proposed methodology shows not only the applicability in tobacco samples, but also demonstrates a guideline to an efficient performance of multi-analytes target analysis using the flow injection mass spectrometry with reliable and robust validation steps. Graphical abstract fx1 Highlights • The method provide high repeatability and reproducibility, within 2 minutes. • HTS-FIA-HRMS was used to calibrate 27 analytes from Tobacco Industry interest. • Models were validated by control samples, blind test and two equipment comparison. • Target models were used in routine samples enabling a tobacco type grouping. [ABSTRACT FROM AUTHOR]

Abstract In this work, we analyzed the performance of the Electro-Filtering Paper Spray Ionization (EFSI) method for detecting compounds in unprocessed samples. A relatively rigid and electrically conductive copper filter was used as a substrate to insure sufficient and efficient sample-solvent extraction and to increase the conductivity for paper spraying. The method was demonstrated as applicable for indirect high-throughput analysis of large-volume unprocessed samples, which is not possible with conventional nanoESI or direct paper spray methods. The new method can generate different desired ion signals for a wide range of compounds by selecting different extraction solvents. Moreover, key parameters related to extraction efficiency were optimized in detail to obtain the most satisfactory extraction efficiency during antibiotic analysis. Finally, under optimal conditions, the EFSI method was successfully used to detect four antibiotics in animal products of egg, chicken, and chicken liver, exhibiting good reproducibility with calibration curves between 81.6% and 96.3%, and R2 values above 0.99. Recoveries of 75.0%ￚ94.6% were obtained for the four antibiotics. Hence, the proposed EFSI-MS is a successful, economical, rapid, and high-throughput method that is effective for both unknown and targeted extraction of unprocessed samples by mass spectrometric analysis. Graphical abstract fx1 Highlights • The performance of electro-filtering paper spray ionization is validated. • Rigid copper filter substrate is used for efficient sample-solvent extraction. • The method directly detects large-volume unknown compounds in samples. • A wide range of ions were obtained by changing the extraction solvent. • The method was used to targeted antibiotics analysis in animal products. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Reduction of isoxazoles, such as sulfamethoxazole, by soluble FeII–tiron complex was studied. • Reduction products of the isoxazoles were mainly ring-cleavage analogs. • The types of complexes formed between isoxazoles and FeII–tiron largely determined the reaction kinetics. • Electron transfer was found to be the rate-limiting step. Abstract Isoxazole (ISX) is a key moiety in a number of antibiotics and pesticides such as sulfamethoxazole. Various ISXs were found to be reduced at different rates in aqueous solution containing FeII and tiron (a catecholate ligand), and the reduction products were identified by time-of-flight mass spectrometry to be the ring-cleavage analogs. Three types of complexes were found to likely form between ISXs and FeII–tiron species: type I forms through 3-N and ring-O; type II forms through 5-N/O and ring-N; and type III forms through 6-O and ring-N. Calculation results indicate that electron transfer (either 1st or 2nd), not protonation or N–O bond dissociation, is most likely the rate-limiting step. Because of the much lower free energies of the complexes formed after ring cleavage than before ring cleavage, the complexation should occur either after or during ring cleavage. The solvent kinetic isotope effects for the reduction of 3-amino-5-methylisoxazole (AMX) and 3,5-dimethylisoxazole (DMX) were determined to be 1.992 ± 0.068 and 1.209 ± 0.079, respectively, indicating that a proton is likely involved in the rate-limiting step for AMX but not for DMX. Electrochemical cell experiments demonstrated that the electron transfer can be significantly facilitated by type I and type II complexation with 1:2 FeII–tiron complex, but only to some extent with free FeII. This study provided a promising strategy to apply a highly effective and low cost reductant for the removal of emerging contaminants from anoxic environments. [ABSTRACT FROM AUTHOR]

The antibacterial activity of camel milk β-casein and its peptic hydrolysate was investigated. The hydrolysate was fractionated by ultrafiltration successively through membranes with a 10 kDa and a 1 kDa cut-off, sequentially. Antibacterial activity assays against Staphylococcus aureus CNRZ 3, Listeria innocua ATCC 33090 and Escherichia coli ATCC 25922 were performed. The growth of S . aureus and L . innocua strain was not inhibited by β-casein; E . coli strain growth was slightly inhibited. All fractions of hydrolysates exhibited some anti-bacterial activity and molecular mass fraction <1 kDa was the most active against both Gram-positive bacterial strains. Mass spectrometry analysis revealed that this fraction contained 129 peptides. Interestingly, 2 of them, f(193–204) and f(193–213), presented at least 50% homology with casecidins 15 and 17 from bovine β-casein. This is the first study reporting the presence of two putative antibacterial fragments in camel β-casein peptic hydrolysate. [ABSTRACT FROM AUTHOR]

Swab touch spray ionization mass spectrometry, an ambient ionization technique, has been applied to the analysis of six explosives from various surfaces including glass, metal, Teflon, plastic, human hands and three types of gloves (nitrile, vinyl and latex). A swab, attached to a metallic handle, was used to sample explosive residues and acted as the ion source. The explosives, 1,3,5‐trinitro‐1,3,5‐triazinane (RDX), 1,3,5,7‐tetranitro‐1,3,5,7‐tetrazocane (HMX), and 2,2‐bis[(nitrooxy)methyl]propane‐1,3‐diyl dinitrate (PETN) had an absolute limit of detection of 10 ng from all the surfaces except for PETN from the nitrile gloves (limit of detection 100 ng). Sodium perchlorate, 2‐methyl‐1,3,5‐trinitrobenzene (TNT) and tetra‐butylammonium perchlorate had limits of detection of 100 pg, 10 pg, and 1 pg, respectively from all surfaces. This study demonstrates the feasibility of swab touch spray ionization mass spectrometry for detection of a wide array of explosives from a variety of forensically applicable surfaces with disposable, commercial, tamperproof and individually‐wrapped conductive swabs without complicated/lengthy sample preparations or extractions. [ABSTRACT FROM AUTHOR]

Abstract A novel method of measuring concentrations of ionized molecules in gases that enables detection of individual ionized molecules by means of tagging them with readily detectable nano-objects has been recently discovered and developed. The femtoampere detection level of this method has been demonstrated. Here we confirm that this detection level is caused by cosmic rays and suggest ways to reduce it. The method was shown to be able to detect 1 ion in 104 cm3 of air in an underground laboratory where the cosmic rays level is negligible. This is an extremely low electric current down to zeptoampere level (1 zA = 10−21 A). This concept opens doors for advances in detection sensitivity in chemistry, biology, medicine and physics. For example for mass spectrometry this method may increase sensitivity of the absolute current detection (for Faraday collector detectors) by two to three orders of magnitude. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS) is a powerful analytical tool that can detect and identify multiple kinds of compounds such as biomolecules with high sensitivity. Recently, various nanoporous solid substrates have been developed for organic-matrix-free laser desorption/ionization (LDI) of analytes. In this study, periodic mesoporous organosilica (PMO) films are demonstrated for the first time to be promising as solid substrates for LDI mass spectrometry (LDI-MS). UV-absorbing PMO thin films having surface open pores with diameters of 20–30 nm are prepared using a triphenylamine derivative as a precursor and an amphiphilic block copolymer as a structure-directing template, followed by nanoscale surface etching. Peptide analytes introduced into the mesopores can be efficiently detected on the order of sub-picomole without the addition of an organic matrix. In addition, the PMO film shows an advantage of superior shot-to-shot reproducibility compared to a conventional matrix-assisted LDI (MALDI) method on a simple and easy way. PMO films with high tunability of framework composition and functionality may pave the way to new solid substrates for LDI-MS. [ABSTRACT FROM AUTHOR]

In this article, some recent trends and developments in ambient desorption/ionization mass spectrometry (ADI-MS) are reviewed, with a special focus on quantitative analyses with direct, open-air sampling. Accurate quantification with ADI-MS is still not routinely performed, but this aspect is considered of utmost importance for the advancement of the field. In fact, several research groups are devoted to the development of novel and optimized ADI-MS approaches. Some key trends include novel sample introduction strategies for improved reproducibility, tailored sample preparation protocols for removing the matrix and matrix effects, and multimode ionization sources. In addition, there is significant interest in quantitative mass spectrometry imaging.Conceptual diagram of the ambient desorption/ionization mass spectrometry approach with different desorption/ionization probes [ABSTRACT FROM AUTHOR]

The asymmetric Pictet–Spengler (P‐S) reaction of chiral Nb‐ethynyl‐substituted tryptophan methyl ester derivatives (from both d‐ and l‐tryptophan) with a simple aliphatic aldehyde, exhibited unprecedented selectivity towards either of the diastereomeric products. A simple variation of conditions could alter the outcome of the cyclization from either 100 % trans‐selective to 100 % cis‐selective originating entirely from internal asymmetric induction under mild conditions. This resulted in a highly efficient access to both 1,3‐cis‐(1,2,3‐trisubstituted tetrahydro‐β‐carbolines, THβCs) and 1,3‐trans‐(1,2,3‐trisubstituted THβCs). To the best of our knowledge, this type of stereocontrol has never been observed from tryptophan methyl ester derivatives (either D or L) in accessing either 1,3‐disubstituted or 1,2,3‐trisubstituted THβCs. By exploiting this very useful ambidextrous diastereoselectivity, we have set the crucial C‐3 and C‐5 stereocenters of C‐19 methyl‐substituted sarpagine/macroline/ajmaline alkaloids beginning with the DNA‐encoded and cheaper l‐(–)‐tryptophan, as well as optionally from commercially available d‐(+)‐tryptophan. [ABSTRACT FROM AUTHOR]

Apolipoprotein E (apoE) is a forefront actor in the transport of lipids and the maintenance of cholesterol homeostasis, and is also strongly implicated in Alzheimer’s disease. Upon lipid-binding apoE adopts a conformational state that mediates the receptor-induced internalization of lipoproteins. Due to its inherent structural dynamics and the presence of lipids, the structure of the biologically active apoE remains so far poorly described. To address this issue, we developed an innovative hybrid method combining experimental data with molecular modeling and dynamics to generate comprehensive models of the lipidated apoE4 isoform. Chemical cross-linking combined with mass spectrometry provided distance restraints, characterizing the three-dimensional organization of apoE4 molecules at the surface of lipidic nanoparticles. The ensemble of spatial restraints was then rationalized in an original molecular modeling approach to generate monomeric models of apoE4 that advocated the existence of two alternative conformations. These two models point towards an activation mechanism of apoE4 relying on a regulation of the accessibility of its receptor binding region. Further, molecular dynamics simulations of the dimerized and lipidated apoE4 monomeric conformations revealed an elongation of the apoE N-terminal domain, whereby helix 4 is rearranged, together with Arg172, into a proper orientation essential for lipoprotein receptor association. Overall, our results show how apoE4 adapts its conformation for the recognition of the low density lipoprotein receptor and we propose a novel mechanism of activation for apoE4 that is based on accessibility and remodeling of the receptor binding region. [ABSTRACT FROM AUTHOR]

Ambient ionization mass spectrometry (AI-MS), the ionization of samples under ambient conditions, enables fast and simple analysis of samples without or with little sample preparation. Due to their simple construction and low resource consumption, plasma-based ionization methods in particular are considered ideal for use in mobile analytical devices. However, systematic investigations that have attempted to identify the optimal configuration of a plasma source to achieve the sensitive detection of target molecules are still rare. We therefore used a low-temperature plasma ionization (LTPI) source based on dielectric barrier discharge with helium employed as the process gas to identify the factors that most strongly influence the signal intensity in the mass spectrometry of species formed by plasma ionization. In this study, we investigated several construction-related parameters of the plasma source and found that a low wall thickness of the dielectric, a small outlet spacing, and a short distance between the plasma source and the MS inlet are needed to achieve optimal signal intensity with a process-gas flow rate of as little as 10 mL/min. In conclusion, this type of ion source is especially well suited for downscaling, which is usually required in mobile devices. Our results provide valuable insights into the LTPI mechanism; they reveal the potential to further improve its implementation and standardization for mobile mass spectrometry as well as our understanding of the requirements and selectivity of this technique.Optimized parameters of a dielectric barrier discharge plasma for ionization in mass spectrometry. The electrode size, shape, and arrangement, the thickness of the dielectric, and distances between the plasma source, sample, and MS inlet are marked in red. The process gas (helium) flow is shown in black [ABSTRACT FROM AUTHOR]

The content of non-metallic impurities in high-purity tetramethylammonium hydroxide (HPTMAH) aqueous solution has an important influence on the yield, electrical properties and reliability of the integrated circuit during the process of chip etching and cleaning. Therefore, an efficient analytical method to directly quantify the content of non-metallic impurities in HPTMAH aqueous solutions is necessary. The present study was aimed to develop a novel method that can accurately determine seven non-metallic impurities (B, Si, P, S, Cl, As, and Se) in an aqueous solution of HPTMAH by inductively coupled plasma tandem mass spectrometry (ICP-MS/MS). The samples were measured using a direct injection method. In the MS/MS mode, oxygen and hydrogen were used as reaction gases in the octopole reaction system (ORS) to eliminate mass spectral interferences during the analytical process. The detection limits of B, Si, P, S, Cl, As, and Se were 0.31, 0.48, 0.051, 0.27, 3.10, 0.008, and 0.005 μg L −1 , respectively. The samples were analyzed by the developed method and the sector field inductively coupled plasma mass spectrometry (SF-ICP-MS) was used for contrastive analysis. The values of these seven elements measured using ICP-MS/MS were consistent with those measured by SF-ICP-MS. The proposed method can be utilized to analyze non-metallic impurities in HPTMAH aqueous solution. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to screen for differentially expressed proteins in the cerebrospinal fluid (CSF) of patients with Guillain-Barré syndrome (GBS). The identification of differentially expressed protein can provide new targets for understanding the pathogenic mechanism, early clinical diagnosis, prognosis and for measuring the effectiveness of interventions. We enrolled 50 GBS patients and 50 meningitis patients (control group) to compare protein expression in CSF. The GBS cases included 28 cases of acute inflammatory demyelinating polyneuropathy (AIDP) and 22 cases of acute motor axonal neuropathy (AMAN). We then performed two-dimensional differential in-gel electrophoresis combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to identify the differentially expressed proteins. The expression levels were validated by ELISA, and their accuracy, sensitivity, and specificity in GBS diagnosis were analyzed by the receiver operating characteristic curve. Three differentially expressed proteins were identified, including the upregulated haptoglobin (Hp) and heat shock protein 70 (Hsp70), and downregulated cystatin C. There were no significant differences between the AIDP and AMAN patients in the positive rates and quantitative expression levels of the three differentially expressed proteins. The accuracy of Hp in the diagnosis of GBS was 0.835, sensitivity was 86.7%, and specificity was 88.2%. The accuracy of cystatin C in the diagnosis of GBS was 0.827, sensitivity was 85.5%, and specificity was 89.7%. The accuracy of Hsp70 in the diagnosis of GBS was 0.841, its sensitivity was 87.8%, and its specificity was 92.3%. Hp and Hsp70 are significantly increased, and cystatin C is downregulated in CSF of GBS patients, which provides important biomarkers for early GBS diagnosis, although these proteins cannot distinguish AIDP and AMAN. [ABSTRACT FROM AUTHOR]

In this study, a simple and rapid reversed phase high performance liquid chromatography with ultraviolet detection (HPLC-UV) method was developed and validated for the simultaneous analysis of erythrodiol, tocopherols, phytosterols and squalene in olive oil and olive pomace oil chemical and physical refining by-products. A sample pretreatment without saponification, solely based on n -hexane extraction, allowed direct analysis of the target compounds from the by-product samples. α-tocopherol, β-sitosterol and squalene were quantified by external calibration. The highest concentrations of these compounds were found in olive oil chemical refining by products (i.e. 0.19%, 4.1% and 19.1% m/m, respectively). Afterwards, the method was adapted to high performance liquid chromatography with electrospray ionisation mass spectrometry detection (HPLC–MS). Positive ESI (+ESI) allowed better sensitivity than negative ESI (−ESI), and detection of all the target compounds except squalene. In addition to α-tocopherol and β-sitosterol, the presence of erythrodiol in the complex by-product samples could be confirmed due to the excellent selectivity of MS detection. [ABSTRACT FROM AUTHOR]

Neuropeptides are short peptides in the range of 3-40 residues that are secreted for cell-cell communication in neuroendocrine systems. In the nervous system, neuropeptides comprise the largest group of neurotransmitters. In the endocrine system, neuropeptides function as peptide hormones to coordinate intercellular signaling among target physiological systems. The diversity of neuropeptide functions is defined by their distinct primary sequences, peptide lengths, proteolytic processing of pro-neuropeptide precursors, and covalent modifications. Global, untargeted neuropeptidomics mass spectrometry is advantageous for defining the structural features of the thousands to tens of thousands of neuropeptides present in biological systems. Defining neuropeptide structures is the basis for defining the proteolytic processing pathways that convert pro-neuropeptides into active peptides. Neuropeptidomics has revealed that processing of pro-neuropeptides occurs at paired basic residues sites, and at non-basic residue sites. Processing results in neuropeptides with known functions and generates novel peptides representing intervening peptide domains flanked by dibasic residue processing sites, identified by neuropeptidomics. While very short peptide products of 2-4 residues are predicted from pro-neuropeptide dibasic processing sites, such peptides have not been readily identified; therefore, it will be logical to utilize metabolomics to identify very short peptides with neuropeptidomics in future studies. Proteolytic processing is accompanied by covalent post-translational modifications (PTMs) of neuropeptides comprising C-terminal amidation, N-terminal pyroglutamate, disulfide bonds, phosphorylation, sulfation, acetylation, glycosylation, and others. Neuropeptidomics can define PTM features of neuropeptides. In summary, neuropeptidomics for untargeted, global analyses of neuropeptides is essential for elucidation of proteases that generate diverse neuropeptides for cell-cell signaling.ᅟ [ABSTRACT FROM AUTHOR]

Thermally triggered drug release from temperature-sensitive liposomes (TSL) holds great promise for cancer therapy. Different types of TSL have been designed recently for heat triggered drug release inside tumor blood vessels or after accumulation into the tumor interstitium. However, justification of drug release profiles is for far mainly based on in vitro release data. While these methods could be good enough to give early indication about the thermal sensitivity of TSL, they are still far from being optimum. This is because these methods do not take into consideration the actual adsorption of proteins onto the surface of TSL after their in vivo administration, also known as “protein corona” and the influence this could have on drug release. Therefore, in this study we compared thermal triggered drug release profile of two different types of doxorubicin encapsulated TSL; namely the lysolipid-containing TSL (LTSL) and traditional TSL (TTSL) after their in vivo recovery from the blood circulation of CD-1 mice. Ex vivo release profile at 42 °C was then tested either in the presence of full plasma or after removal of unbound plasma proteins (i.e. protein corona coated TSL). Our data showed that the influence of the environment on drug release profile was very much dependent on the type of TSL. LTSL release profile was consistently characterized by ultrafast drug release independent on the conditions tested. On the contrary, TTSL release profile changed significantly. Doxorubicin release from in vivo recovered TTSL was slow and incomplete in the presence of unbound plasma proteins, whereas very rapid drug release was detected from in vivo recovered and purified protein corona-coated TTSL in the absence of unbound proteins. Using mass spectrometry and quantification of protein adsorption, we confirmed that this discrepancy is due to the changes in protein adsorption onto TTSL when heated in the presence of unbound proteins leading to reduction in drug release. In summary this study showed that the formation of the in vivo corona on TSL will have a dramatic impact on their release profile and is dependent on both their lipid composition and the protein content of the environment in which drug release is triggered. [ABSTRACT FROM AUTHOR]

The chemical structure of x11564, a new endogenous organosulfur metabolite, was elucidated by de novo interpretation of mass spectrometric data. The structure was confirmed by comparison to a synthetic standard. Metabolite x11564 is structurally related to intermediates in the methionine salvage pathway. [ABSTRACT FROM AUTHOR]

High resolution mass spectrometry and modern data independent acquisition (DIA) methods enable the creation of general unknown screening (GUS) procedures. However, even when DIA is used, its potential is far from being exploited, because often, the untargeted acquisition is followed by a targeted search. Applying an actual GUS (including untargeted screening) produces an immense amount of data that must be dealt with. An optimization of the parameters regulating the feature detection and hit generation algorithms of the data processing software could significantly reduce the amount of unnecessary data and thereby the workload. Design of experiment (DoE) approaches allow a simultaneous optimization of multiple parameters. In a first step, parameters are evaluated (crucial or noncrucial). Second, crucial parameters are optimized. The aim in this study was to reduce the number of hits, without missing analytes. The obtained parameter settings from the optimization were compared to the standard settings by analyzing a test set of blood samples spiked with 22 relevant analytes as well as 62 authentic forensic cases. The optimization lead to a marked reduction of workload (12.3 to 1.1% and 3.8 to 1.1% hits for the test set and the authentic cases, respectively) while simultaneously increasing the identification rate (68.2 to 86.4% and 68.8 to 88.1%, respectively). This proof of concept study emphasizes the great potential of DoE approaches to master the data overload resulting from modern data independent acquisition methods used for general unknown screening procedures by optimizing software parameters. [ABSTRACT FROM AUTHOR]

An important aim of proteogenomics, which combines data of high throughput nucleic acid and protein analysis, is to reliably identify single amino acid substitutions representing a main type of coding genome variants. Exact knowledge of deviations from the consensus genome can be utilized in several biomedical fields, such as studies of expression of mutated proteins in cancer, deciphering heterozygosity mechanisms, identification of neoantigens in anticancer vaccine production, search for RNA editing sites at the level of the proteome, etc. Generation of this new knowledge requires processing of large data arrays from high-resolution mass spectrometry, where information on single-point protein variation is often difficult to extract. Accordingly, a significant problem in proteogenomic analysis is the presence of high levels of false positive results for variant-containing peptides in the produced results. Here we review recently suggested approaches of high quality proteomics data processing that may provide more reliable identification of single amino acid substitutions, especially contrary to residue modifications occurring in vitro and in vivo. Optimized methods for assessment of false discovery rate save instrumental and computational time spent for validation of interesting findings of amino acid polymorphism by orthogonal methods. [ABSTRACT FROM AUTHOR]

The present review focus on the analytical platforms and the workflow for toxicometabolomics with a special emphasis on their strengths and pitfalls presenting as a case study the toxicometabolomics of arsenic in mammals. Although powerful analytical methods and techniques are currently available for metabolomics, the main “bottleneck” is still the absence of unified protocols for sample preparation (e.g. quenching, solvents used) as well as several important factors in toxicometabolomics, which drastically affect the metabolism (e.g. selection of model organisms, xenobiotic doses, chemical form of the xenobiotic, exposure route, biological sample). In this context, the applicability to complex samples, higher sensitivity, specificity and the possibility to perform quantitative analysis offered by MS is crucial to probe xenobiotic induced metabolic changes to evaluate the stress responses. Nowadays, the use of different metabolomic platforms allowed determining important changes in the metabolism induced by arsenic in mammals such as alterations in the energy (e.g. Glycolysis, Kreb's cycle), amino acid, lipid, nucleotide and androgen metabolisms. [ABSTRACT FROM AUTHOR]

Summary: Background: In spite of extensive regulation to limit exposure, nickel remains the main cause of contact allergy in the general population. More detailed knowledge on the skin uptake of haptens is required. So far, no method exists for the visualization of this clinically relevant hapten and its distribution in the skin. Objectives: To show, in terms of a proof of concept, that imaging mass spectrometry [time of flight secondary ion mass spectrometry (ToF‐SIMS)] can be applied for investigation of the penetration and distribution of nickel in human skin. Method: Full‐thickness human skin obtained from breast reduction surgery was exposed to nickel sulfate (5% in deionized water) for 24 h in Franz‐type diffusion cells. Biopsies were obtained from nickel‐treated samples and control (deionized water). The tissue was sliced, and analysed with ToF‐SIMS, generating high‐resolution images of ion distribution in the epidermis and upper dermis. Results: The skin layers could be discerned from the ToF‐SIMS data, particularly on the basis of the collagen signal. Nickel ions were localized to the stratum corneum and upper epidermis. Conclusions: This is the first time that ToF‐SIMS has been applied to trace the distribution of a hapten in human skin. Proof of principle was shown for nickel, and the technique can, in the future, be expanded for investigation of the skin distribution of clinically relevant sensitizers in general. [ABSTRACT FROM AUTHOR]

11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1; EC 1.1.1.146) generates active glucocorticoid hormones. Small molecule inhibitors have been developed to target 11β-HSD1 for the treatment of dementia; these must enter brain subregions, such as the hippocampus, to be effective. We previously reported mass spectrometry imaging measurement of murine tissue steroids, and deuterated steroid tracer infusion quantification of 11β-HSD1 turnover in humans. Here, these tools are combined to assess tissue pharmacokinetics and pharmacodynamics of an 11β-HSD1 inhibitor that accesses the brain. [9,11,12,12- 2 H] 4 -Cortisol was infused (1.75 mg/day) by minipump for 2 days into C57Bl6 mice (male, age 12 weeks, n = 3/group) after which an 11β-HSD1 inhibitor (UE2316) was administered (25 mg/kg oral gavage) and animals culled immediately or 1, 2 and 4 h post-dosing. Mice with global genetic disruption of Hsd11B1 were studied similarly. Turnover of d4-cortisol to d3-cortisone (by loss of the 11-deuterium) and regeneration of d3-cortisol (by 11β-HSD1-mediated reduction) were assessed in plasma, liver and brain using matrix assisted laser desorption ionization coupled to Fourier transform cyclotron resonance mass spectrometry. The tracer d4-cortisol was detected in liver and brain following a two day infusion. Turnover to d3-cortisone and on to d3-cortisol was slower in brain than liver. In contrast, d3-cortisol was not detected in mice lacking 11β-HSD1. UE2316 impaired d3-cortisol generation measured in whole body (assessed in plasma; 53.1% suppression in rate of appearance in d3-cortisol), liver and brain. Differential inhibition in brain regions was observed; active glucocorticoids were suppressed to a greater in extent hippocampus or cortex than in amygdala. These data confirm that the contribution of 11β-HSD1 to the tissue glucocorticoid pool, and the consequences of enzyme inhibition on active glucocorticoid concentrations, are substantial, including in the brain. They further demonstrate the value of mass spectrometry imaging in pharmacokinetic and pharmacodynamic studies. [ABSTRACT FROM AUTHOR]

Diarylheptanoids are a group of secondary metabolites widely distributed in the Betulaceae family and characteristic for Alnus species. In this study, the chemotaxonomic power of diarylheptanoids, such as hirsutanonol-5-O-β-d-glucopyranoside, rubranoside A, oregonin, platyphylloside, alnuside A and hirsutanonol, has been investigated in combination with principal component analysis (PCA) for differentiation of Alnus species. Concentrations of six diarylheptanoids in the bark extracts of two natural populations of Alnus glutinosa (black alder) and Alnus incana (gray alder) were determined by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). PCA clearly shows the separation of three groups. Populations I (A. glutinosa) and II (A. incana) both consisted of individuals of the corresponding species. Four individuals from both sampled populations formed a separate group (population III), which possibly represents a hybrid group. Accordingly, diarylheptanoids may serve in combination with PCA as chemotaxonomic markers at the species level, which may also reveal hybrid species. [ABSTRACT FROM AUTHOR]

Th/U radiochronometer was commonly used for uranium age determination which could help to reveal the origin of the nuclear material. Th was a relatively appropriate spike for measuring Th by isotope dilution mass spectrometry and its concentration needs to be calibrated before using as spike. A prepared Th solution which was used as Th isotope spike for age dating of CRM U850 sample were calibrated separately by Th and Th standard materials. The calibrated results were compared and evaluated. [ABSTRACT FROM AUTHOR]

Background: The smart control for food and feed technologies consist in the development of new methods that facilitate the control of productive processes guaranteeing the quality and safety of agrofood products. The importance given to this research line is a clear indicator of the interest of all of the agents implicated in promoting the introduction of innovative technologies. The goal is to implement new, fast, economical, analytical techniques, which constitute a real alternative to traditional control procedures. Objective: The aim of this study was to evaluate the use of an electronic sensor based on the impedance spectroscopy technique for the characterization of hams during the post-salting step (8, 10, 12 and 14 weeks). Materials and methods: 60 hams from three different categories (fat, semi-fat and lean), were tray salted under the conditions of a company (xNaCl = 0.11 g/g dry matter). For each time, samples were first evaluated with the electronic method (non-destructive analysis) and then analytical determinations of: mass variation, moisture content, fat content, salt content and water activity were performed on each ham in different zones. The electric data were evaluated using Principal Component Analysis (PCA) and regression with Partial Least Squares (PLS) through the analytical data. Results: The PCA analysis discriminated between the different evaluated zones. At eighth week 79.06% of the variance was explained and at tenth week, the 82.53%. No relation was observed for the different ham categories. The correlation between the impedance signal and the analytical determinations showed the best cross validation coefficient (R2CV) values for moisture content (0.75) and water activity (0.73). Conclusions: The impedance spectroscopy technique generated different signals between the zones of analysis during the first two post-salting times, eight and ten weeks, in which physicochemical differences were also observed as a consequence of the variation in the salt concentration between zones. [ABSTRACT FROM AUTHOR]

In their article, Morris and Baladandayuthapani clearly evidence the influence of statisticians in recent methodological advances throughout the bioinformatics pipeline and advocate for the expansion of this role. The latest acquisition platforms, such as next generation sequencing (genomics/transcriptomics) and hyphenated mass spectrometry (proteomics/metabolomics), output raw datasets in the order of gigabytes; it is not unusual to acquire a terabyte or more of data per study. The increasing computational burden this brings is a further impediment against the use of statistically rigorous methodology in the pre-processing stages of the bioinformatics pipeline. In this discussion I describe the mass spectrometry pipeline and use it as an example to show that beneath this challenge lies a two-fold opportunity: (a) Biological complexity and dynamic range is still well beyond what is captured by current processing methodology; hence, potential biomarkers and mechanistic insights are consistently missed; (b) Statistical science could play a larger role in optimizing the acquisition process itself. Data rates will continue to increase as routine clinical omics analysis moves to large-scale facilities with systematic, standardized protocols. Key inferential gains will be achieved by borrowing strength across the sum total of all analyzed studies, a task best underpinned by appropriate statistical modelling. [ABSTRACT FROM AUTHOR]

Exhaled breath is a body secretion, and the sampling process of this is simple and cost effective. It can be non-invasively collected for diagnostic procedures. Variations in the chemical composition of exhaled breath resulting from gaseous exchange in the extensive capillary network of the body are proposed to be associated with pathophysiological changes. In light of the foreseeable potential of exhaled breath as a diagnostic specimen, we used gas chromatography and mass spectrometry (GC-MS) to study the chemical compounds present in exhaled breath samples from patients with Alzheimer's disease (AD), Parkinson's disease (PD), and from healthy individuals as a control group. In addition, we also designed and developed a chemical-based exhaled breath sensor system to examine the distribution pattern in the patient and control groups. The results of our study showed that several chemical compounds, such as 1-phenantherol and ethyl 3-cyano-2,3-bis (2,5,-dimethyl-3-thienyl)-acrylate, had a higher percentage area in the AD group than in the PD and control groups. These results may indicate an association of these chemical components in exhaled breath with the progression of disease. In addition, in-house fabricated exhaled breath sensor systems, containing several types of gas sensors, showed significant differences in terms of the normalized response of the sensitivity characteristics between the patient and control groups. A subsequent clustering analysis was able to distinguish between the AD patients, PD patients, and healthy individuals using principal component analysis, Sammon's mapping, and a combination of both methods, in particular when using the exhaled breath sensor array system A consisting of eight sensors. With this in mind, the exhaled breath sensor system could provide alternative option for diagnosis and be applied as a useful, effective tool for the screening and diagnosis of AD in the near future. [ABSTRACT FROM AUTHOR]

Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined. We found that linagliptin, a DPP-4 inhibitor, suppressed capillary rarefaction in the hearts of mice with dietary obesity. Metabolomic analysis performed with capillary electrophoresis/mass spectrometry (LC-MS/MS) showed that linagliptin promoted favorable metabolic remodeling in cardiac tissue, which was characterized by high levels of citrulline and creatine. DNA microarray analysis revealed that the cardiac tissue level of early growth response protein 1 (EGR-1), which activates angiogenesis, was significantly reduced in untreated mice with dietary obesity, while this decrease was inhibited by administration of linagliptin. Mature fibroblast growth factor 2 (FGF-2) has a putative truncation site for DPP-4 at the NH2-terminal, and LC-MS/MS showed that recombinant DPP-4 protein cleaved the NH2-terminal dipeptides of mature FGF-2. Incubation of cultured neonatal rat cardiomyocytes with FGF-2 increased Egr1 expression, while it was suppressed by recombinant DPP-4 protein. Furthermore, vascular endothelial growth factor-A had a critical role in mediating FGF-2/EGR-1 signaling. In conclusion, pharmacological inhibition of DPP-4 suppressed capillary rarefaction and contributed to favorable remodeling of cardiac metabolism in mice with dietary obesity. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide. We validated the utility of plasma metabolomics analysis in the clinical diagnosis of acute TBI in a rat model of controlled cortical impact (CCI) using gas chromatography/mass spectrometry (GC/MS). Thirty Sprague-Dawley rats were randomly divided into two groups of 15 rats each: the CCI group and sham group. Blood samples were obtained from the rats within the first 24 h after TBI injury. GC/MS measurements were performed to evaluate the profile of acute TBI-induced metabolic changes, resulting in the identification of 45 metabolites in plasma. Principal component analysis, partial least squares-discriminant analysis, orthogonal partial least square discriminant analysis using hierarchical clustering and univariate/multivariate analyses revealed clear differences in the plasma metabolome between the acute CCI group and the sham group. CCI induced distinctive changes in metabolites including linoleic acid metabolism, amino acid metabolism, galactose metabolism, and arachidonic acid metabolism. Specifically, the acute CCI group exhibited significant alterations in proline, phosphoric acid, β-hydroxybutyric acid, galactose, creatinine, L-valine, linoleic acid and arachidonic acid. A receiver operating characteristic curve analysis showed that the above 8 metabolites in plasma could be used as the potential biomarkers for the diagnosis of acute TBI. Furthermore, this study is the first time to identify the galactose as a biomarker candidate for acute TBI. This comprehensive metabolic analysis complements target screening for potential diagnostic biomarkers of acute TBI and enhances predictive value for the therapeutic intervention of acute TBI. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy ( PVR) develops as a complication of retinal detachment surgery and represents a devastating condition leading to serious vision loss. A good animal model that permits extensive functional studies and drug testing is crucial in finding better therapeutic modalities for PVR. A previously established mouse model, using dispase injection, was analyzed from the proteomic point of view, examining global protein profile changes by 2D electrophoresis, image analysis and HPLC-tandem mass spectrometry-based protein identification. The easy applicability of the mouse model was used to study the role of transglutaminase 2 ( TG2) in PVR formation by proteomic examination of dispase-induced TG2 knockout vitreous samples. Our data demonstrate that, despite the altered appearance of crystallin proteins, the lack of TG2 did not prevent the development of PVR. [ABSTRACT FROM AUTHOR]

An analytical technique is proposed to determine ultratrace concentrations of Mo, V, and W found in seawater using mass spectrometry with inductively coupled plasma (ICP MS) after preliminary concentration by solid-phase extraction of metal complexes with 8-hydroxyquinoline (8-HQ) on C18 octadecyl silica. The technique utilizes 150 mL of a water sample. A preconcentration factor 50 is obtained. The detection limits are 0.25 nmol/kg, 0.041 nmol/kg, and 5 pmol/kg for Mo, V, and W, respectively. Dissolved Mo, V, and Wconcentrations in surface seawater from Atlantic Ocean transect were determined. The concentrations ranges along the transect were: 91-108 nmol/kg for Mo, 28-35 nmol/kg for V, and 55-75 pmol/kg for W. The Mo/W ratio varied from 1300 to 1800. [ABSTRACT FROM AUTHOR]