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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 865 records · Page 48

Gas-phase ion-molecule interactions in a collision reaction cell with triple quadrupole-inductively coupled plasma mass spectrometry: Investigations with N 2 O as the reaction gas

Nitrous oxide (N 2 O) was used as a reaction gas to investigate the gas phase ion-molecule interactions using the Agilent 8900 QQQ-ICP-MS. A multi-element standard containing 45 elements with masses ranging from 9 to 208 u was measured in the presence and absence of N 2 O. The main product ion species observed were oxides and nitrides. Comparison of the N 2 O reaction results with similar measurements conducted with O 2 revealed that N 2 O was more effective at forming oxides in general: the elements Cd and Pb were shown to produce oxides with N 2 O where the reaction did not occur with O 2 . Nitrous oxide was also shown to produce a significant amount of nitride species in a few cases. The general reactivity was shown to be consistent with density functional theory (DFT)-predicted reaction enthalpies, such that all predicted exothermic reactions produced product ions at levels at least 1% of the unreacted ion. Our results show that reaction enthalpy is a reasonable predictor of reactivity with N2O on the timescales of the interactions in non-thermal ICP-MS/MS systems. Our work demonstrates the utility of two relatively new platforms (commercial elemental ICP-MS/MS and EMSL Arrows interface to the NWChem program suite), which allows for the study of a large number of elements within a short period. While DFT with the basis sets utilized here is not the most accurate computational method, it is also not computationally expensive and is shown to be suitable for predicting gas phase reactivity in the QQQ-ICP-MS for the majority of ions studied. Here, the ease and rapidity of data collection and DFT calculations has the potential to be very impactful for the identification of targeted reaction chemistries to be leveraged for analytical method development, such as for the inline separation of isobaric interferences from analytes of interest.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

CD18-mediated adhesion is required for the induction of a proinflammatory phenotype in lung epithelial cells by mononuclear cell-derived extracellular vesicles

Highlights: • Monocytic extracellular vesicles upregulate proinflammatory mediators. • CD18-mediated adhesion to target lung epithelial cells is necessary. • An RGD-containing peptide and an anti-ICAM1 antibody inhibit the phenomenon. Extracellular vesicles are submicron vesicles that upregulate the synthesis of proinflammatory mediators by lung epithelial cells. We investigated whether these structures adhere to lung epithelial cells, and whether adhesion is a prerequisite for their proinflammatory activity. Extracellular vesicles were generated by stimulation of normal human mononuclear cells with the calcium ionophore A23187, and labelled with carboxyfluorescein diacetate succinimidyl ester. Adhesion of vesicles to monolayers of immortalized bronchial epithelial (16HBE) and alveolar (A549) cells was analyzed by fluorescence microscopy. The role of candidate adhesion receptors was evaluated with inhibitory monoclonal antibodies and soluble peptides. The synthesis of proinflammatory mediators was assessed by ELISA. Transmission electron microscopy confirmed the generation of closed vesicles with an approximate size range between 50 and 600 nm. Adhesion of extracellular vesicles to epithelial cells was upregulated upon stimulation of the latter with tumor necrosis factor-α. Adhesion was blocked by an anti-CD18 antibody, by peptides containing the sequence RGD and, to a lesser extent, by an antibody to ICAM-1. The same molecules also blocked the upregulation of the synthesis of interleukin-8 and monocyte chemotactic protein-1 induced by extracellular vesicles. CD18-mediated adhesion of extracellular vesicles is a prerequisite for their proinflammatory activity.

60 APPLIED LIFE SCIENCES↗

SAHA and cisplatin sensitize gastric cancer cells to doxorubicin by induction of DNA damage, apoptosis and perturbation of AMPK-mTOR signalling

Highlights: • Gastric adenocarcinoma cells were sensitized to doxorubicin by histone deacetylase inhibitors and cisplatin. • SAHA synergized with doxorubicin to induce apoptosis in gastric cancer cells. • γH2AX accumulates in doxorubicin-SAHA treatment, but downstream effector 53BP1 and Rad51 protein levels were attenuated. • The drug treatment downregulated AMPK inhibitory phosphorylation on Ser-485. • The drug treatment downregulated mTOR signalling. Chemotherapy remains the most prescribed anti-cancer therapy, despite patients suffering severe side effects and frequently developing chemoresistance. These complications can be partially overcome by combining different chemotherapeutic agents that target multiple biological pathways. However, selecting efficacious drug combinations remains challenging. We previously used fission yeast Schizosaccharomycespombe as a surrogate model to predict drug combinations, and showed that suberoylanilide hydroxamic acid (SAHA) and cisplatin can sensitise gastric adenocarcinoma cells toward the cytotoxic effects of doxorubicin. Yet, how this combination undermines cell viability is unknown. Here, we show that SAHA and doxorubicin markedly enhance the cleavage of two apoptosis markers, caspase 3 and poly-ADP ribose polymerase (PARP-1), and increase the phosphorylation of γH2AX, a marker of DNA damage. Further, we found a prominent reduction in Ser485 phosphorylation of AMP-dependent protein kinase (AMPK), and reductions in its target mTOR and downstream ribosomal protein S6 phosphorylation. We show that SAHA contributes most of the effect, as confirmed using another histone deacetylase inhibitor, trichostatin A. Overall, our results show that the combination of SAHA and doxorubicin can induce apoptosis in gastric adenocarcinoma in a synthetically lethal manner, and that fission yeast offers an efficient tool for identifying potent drug combinations against human cancer cells.

60 APPLIED LIFE SCIENCES↗

Benzo[a]pyrene Induction of Glutathione S-transferases: An activity-based protein profiling investigation

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants generated from combustion of carbon-based matter. Upon ingestion, these molecules can be bioactivated by cytochrome P450 monooxygenases to oxidized toxic metabolites. Some of these metabolites are potent carcinogens that can form irreversible adducts with DNA and other biological macromolecules. Conjugative enzymes, such as glutathione S-transferases or UDP-glucuronosyltransferases, are responsible for the detoxification and/or facilitate the elimination of these carcinogens. While responses to PAH exposures have been extensively studied for the bioactivating cytochrome P450 enzymes, much less is known regarding the response of glutathione S-transferases in mammalian systems. In this study, we investigated the expression and activity responses of murine hepatic glutathione S-transferases to benzo[a]pyrene exposure using global proteomics and activity-based protein profiling for chemoproteomics, respectively. Using this approach, we identified several enzymes exhibiting increased activity including GSTA2, M1, M2, M4, M6, and P1. One enzyme, GSTA4, was found to be highly enzymatically repressed with increasing B[a]P dose. Activity responses of several of these enzymes were identified as being expression-independent when comparing global and activity-based datasets, possibly alluding to as of yet unknown regulatory post-translational mechanisms.

Stoddard, Ethan G.↗

The Curious Case of Pu + : Insight on 5f Orbital Activity from Inductively Coupled Plasma Tandem Mass Spectrometry (ICP-MS/MS) Reactions

A comprehensive understanding of when and how 5f orbitals participate in complex chemical bonding is important for a variety of applications. The actinides are unique in that they possess 5f orbitals and can access high oxidation states, which make them attractive for use in catalysis. Fundamental studies of actinide–ligand interactions offer a mechanism to examine the activation of the 5f orbitals so that the selectivity of 5f orbitals can be assessed. A previous study examined the reaction of Pu + + CO 2 and determined that the reaction efficiency is restricted by a barrier, namely, promotion from the Pu + ground-state configuration, 5f 6 7s, to a reactive-state configuration, 5f 5 6d 2 . Here, the present study illustrates the benefit of activation of Pu’s 5f orbitals when studying the reaction of Pu + + NO. In this reaction, PuO + forms in an exothermic, barrierless process. The 5f orbitals can and do participate in forming a linear intermediate, [N-Pu-O] + , and this drives the exothermic reaction. Understanding the conditions under which 5f orbitals are active in chemical bonding is the key to exploiting the actinides’ selective catalytic capabilities.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗