Carboxylic acids and light interact to affect nanoceria stability and dissolution in acidic aqueous environments

Cerium atoms on the surfaces of nanoceria (i.e., cerium oxide in the form of nanoparticles) can store or release oxygen, cycling between Ce3+ and Ce4+; therefore, they can cause or relieve oxidative stress within living systems. Nanoceria dissolution occurs in acidic environments. Nanoceria stabilization is a known problem even during its synthesis; in fact, a carboxylic acid, namely citric acid, is used in many synthesis protocols. Citric acid adsorbs onto nanoceria surfaces, limiting particle formation and creating stable dispersions with extended shelf life. To better understand factors influencing the fate of nanoceria, its dissolution and stabilization have been previously studied in vitro using acidic aqueous environments. Nanoceria agglomerated in the presence of some carboxylic acids over 30 weeks, and degraded in others, at pH 4.5 (i.e., the pH value in phagolysosomes). Plants release carboxylic acids, and cerium carboxylates are found in underground and aerial plant parts. To further test nanoceria stability, suspensions were exposed to light and dark conditions, simulating plant environments and biological systems. Light induced nanoceria agglomeration in the presence of some carboxylic acids. Nanoceria agglomeration did not occur in the dark in the presence of most carboxylic acids. Light initiates free radicals generated by ceria nanoparticles. Nanoceria completely dissolved in the presence of citric, malic, and isocitric acid when exposed to light, attributed to nanoceria dissolution, release of Ce3+ ions, and formation of cerium coordination complexes on the ceria nanoparticle surface that inhibit agglomeration. Key functional groups of carboxylic acids that prevented nanoceria agglomeration were identified. A long carbon chain backbone containing a carboxylic acid group geminal to a hydroxy group in addition to a second carboxylic acid group may optimally complex with nanoceria. The results provide mechanistic insight into the role of carboxylic acids in nanoceria dissolution and its fate in soils, plants, and biological systems

Waste Water Brine Purification through Electrodialysis Ion Exchange

Reutilizing resources onboard the International Space Station (ISS) and for future deep space missions are critical for mission longevity and sustainability. Waste water brine produced from water recovery systems contain chemical species that could be processed into a potential fertilizer for future plant systems.Fertilizer production can be achieved through a process called electrodialysis ion exchange. Waste water containing inorganic salt components are fed through a series of ion exchange membranes to produce fertilizer (a phosphate rich stream), electrolysis-grade water, and other useful commodities.A test bed was constructed to conduct controlled experiments and an experimental design procedure developed to determine the feasibility of the process. Conductivity and pH probes were utilized to determine the ion concentration in each of the product streams, along with ion chromatography (IC) to define the exact concentration of each ion in every stream throughout the experiment. This is crucial in order to convey the effectiveness of ion removal from the incoming waste water stream.The waste water and electrolyte streams were prepared in the lab prior to experimentation. Additionally, the ion exchange membrane configurations were developed and Opto 22 data analysis software incorporated to conduct measurements in real time.Ions successfully diffused across their respective membranes into the concentrate, acid, and base streams. This resulted in pure water, a phosphate rich stream, and a separate anion/hydrogen and cation/hydroxide stream

InnateDB: systems biology of innate immunity and beyond—recent updates and continuing curation

peer-reviewedInnateDB (http://www.innatedb.com) is an integrated analysis platform that has been specifically designed to facilitate systems-level analyses of mammalian innate immunity networks, pathways and genes. In this article, we provide details of recent updates and improvements to the database. InnateDB now contains >196 000 human, mouse and bovine experimentally validated molecular interactions and 3000 pathway annotations of relevance to all mammalian cellular systems (i.e. not just immune relevant pathways and interactions). In addition, the InnateDB team has, to date, manually curated in excess of 18 000 molecular interactions of relevance to innate immunity, providing unprecedented insight into innate immunity networks, pathways and their component molecules. More recently, InnateDB has also initiated the curation of allergy- and asthma-related interactions. Furthermore, we report a range of improvements to our integrated bioinformatics solutions including web service access to InnateDB interaction data using Proteomics Standards Initiative Common Query Interface, enhanced Gene Ontology analysis for innate immunity, and the availability of new network visualizations tools. Finally, the recent integration of bovine data makes InnateDB the first integrated network analysis platform for this agriculturally important model organism.This work was supported by Genome BC through the Pathogenomics of Innate Immunity (PI2) project and by the Foundation for the National Institutes of Health and the Canadian Institutes of Health Research under the Grand Challenges in Global Health Research Initiative [Grand Challenges ID: 419]. Further funding was also provided by AllerGen grants 12ASI1 and 12B&B2. D.J.L. was funded in part during this project by a postdoctoral trainee award from the Michael Smith Foundation for Health Research (MSFHR). F.S.L.B. is a MSFHR Senior Scholar and R.E.W.H. holds a Canada Research Chair (CRC). Funding to enable bovine systems biology in InnateDB is provided by Teagasc [RMIS6018] and the Teagasc Walsh Fellowship scheme. IMEx is funded by the European Commission under the PSIMEx project [contract number FP7-HEALTH-2007-223411]. Funding for open access charge: Teagasc [RMIS6018]

Surface-Controlled Dissolution Rates: A Case Study of Nanoceria in Carboxylic Acid Solutions

Nanoparticle dissolution in local milieu can affect their ecotoxicity and therapeutic applications. For example, carboxylic acid release from plant roots can solubilize nanoceria in the rhizosphere, affecting cerium uptake in plants. Nanoparticle dispersions were dialyzed against ten carboxylic acid solutions for up to 30 weeks; the membrane passed cerium-ligand complexes but not nanoceria. Dispersion and solution samples were analyzed for cerium by inductively coupled plasma mass spectrometry (ICP-MS). Particle size and shape distributions were measured by transmission electron microscopy (TEM). Nanoceria dissolved in all carboxylic acid solutions, leading to cascades of progressively smaller nanoparticles and producing soluble products. The dissolution rate was proportional to nanoparticle surface area. Values of the apparent dissolution rate coefficients varied with the ligand. Both nanoceria size and shape distributions were altered by the dissolution process. Density functional theory (DFT) estimates for some possible Ce(IV) products showed that their dissolution was thermodynamically favored. However, dissolution rate coefficients did not generally correlate with energy of formation values. The surface-controlled dissolution model provides a quantitative measure for nanoparticle dissolution rates: further studies of dissolution cascades should lead to improved understanding of mechanisms and processes at nanoparticle surfaces

Influence of the Alternative Sigma Factor RpoN on Global Gene Expression and Carbon Catabolism in Enterococcus faecalis V583

The alternative sigma factor σ54 has been shown to regulate the expression of a wide array of virulence-associated genes, as well as central metabolism, in bacterial pathogens. In Gram-positive organisms, the σ54 is commonly associated with carbon metabolism. In this study, we show that the Enterococcus faecalis alternative sigma factor σ54 (RpoN) and its cognate enhancer binding protein MptR are essential for mannose utilization and are primary contributors to glucose uptake through the Mpt phosphotransferase system. To gain further insight into how RpoN contributes to global transcriptional changes, we performed microarray transcriptional analysis of strain V583 and an isogenic rpoN mutant grown in a chemically defined medium with glucose as the sole carbon source. Transcripts of 340 genes were differentially affected in the rpoN mutant; the predicted functions of these genes mainly related to nutrient acquisition. These differentially expressed genes included those with predicted catabolite-responsive element (cre) sites, consistent with loss of repression by the major carbon catabolite repressor CcpA. To determine if the inability to efficiently metabolize glucose/mannose affected infection outcome, we utilized two distinct infection models. We found that the rpoN mutant is significantly attenuated in both rabbit endocarditis and murine catheter-associated urinary tract infection (CAUTI). Here, we examined a ccpA mutant in the CAUTI model and showed that the absence of carbon catabolite control also significantly attenuates bacterial tissue burden in this model. Our data highlight the contribution of central carbon metabolism to growth of E. faecalis at various sites of infection

Carboxylic Acids Accelerate Acidic Environment-Mediated Nanoceria Dissolution

Ligands that accelerate nanoceria dissolution may greatly affect its fate and effects. This project assessed the carboxylic acid contribution to nanoceria dissolution in aqueous, acidic environments. Nanoceria has commercial and potential therapeutic and energy storage applications. It biotransforms in vivo. Citric acid stabilizes nanoceria during synthesis and in aqueous dispersions. In this study, citrate-stabilized nanoceria dispersions (∼4 nm average primary particle size) were loaded into dialysis cassettes whose membranes passed cerium salts but not nanoceria particles. The cassettes were immersed in iso-osmotic baths containing carboxylic acids at pH 4.5 and 37 °C, or other select agents. Cerium atom material balances were conducted for the cassette and bath by sampling of each chamber and cerium quantitation by ICP-MS. Samples were collected from the cassette for high-resolution transmission electron microscopy observation of nanoceria size. In carboxylic acid solutions, nanoceria dissolution increased bath cerium concentration to \u3e96% of the cerium introduced as nanoceria into the cassette and decreased nanoceria primary particle size in the cassette. In solutions of citric, malic, and lactic acids and the ammonium ion ∼15 nm, ceria agglomerates persisted. In solutions of other carboxylic acids, some select nanoceria agglomerates grew to ∼1 micron. In carboxylic acid solutions, dissolution half-lives were 800–4000 h; in water and horseradish peroxidase they were ≥55,000 h. Extending these findings to in vivo and environmental systems, one expects acidic environments containing carboxylic acids to degrade nanoceria by dissolution; two examples would be phagolysosomes and in the plant rhizosphere

Simulated Biological Fluid Exposure Changes Nanoceria’s Surface Properties but not its Biological Response

Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce3+ and Ce4+, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria’s surface properties and biological activity. This was investigated by measuring the physicochemical properties of nanoceria with a citric acid coating (size; morphology; crystal structure; surface elemental composition, charge, and functional groups; and weight) before and after exposure to simulated lung, gastric, and intestinal fluids. SBF-exposed nanoceria biological effect was assessed as A549 or Caco-2 cell resazurin metabolism and mitochondrial oxygen consumption rate. SBF exposure resulted in loss or overcoating of nanoceria’s surface citrate, greater nanoceria agglomeration, deposition of some SBF components on nanoceria’s surface, and small changes in its zeta potential. The engineered nanoceria and SBF-exposed nanoceria produced no statistically significant changes in cell viability or cellular oxygen consumption rates

The Preparation Temperature Influences the Physicochemical Nature and Activity of Nanoceria

Cerium oxide nanoparticles, so-called nanoceria, are engineered nanomaterials prepared by many methods that result in products with varying physicochemical properties and applications. Those used industrially are often calcined, an example is NM-212. Other nanoceria have beneficial pharmaceutical properties and are often prepared by solvothermal synthesis. Solvothermally synthesized nanoceria dissolve in acidic environments, accelerated by carboxylic acids. NM-212 dissolution has been reported to be minimal. To gain insight into the role of high-temperature exposure on nanoceria dissolution, product susceptibility to carboxylic acid-accelerated dissolution, and its effect on biological and catalytic properties of nanoceria, the dissolution of NM-212, a solvothermally synthesized nanoceria material, and a calcined form of the solvothermally synthesized nanoceria material (ca. 40, 4, and 40 nm diameter, respectively) was investigated. Two dissolution methods were employed. Dissolution of NM-212 and the calcined nanoceria was much slower than that of the non-calcined form. The decreased solubility was attributed to an increased amount of surface Ce4+ species induced by the high temperature. Carboxylic acids doubled the very low dissolution rate of NM-212. Nanoceria dissolution releases Ce3+ ions, which, with phosphate, form insoluble cerium phosphate in vivo. The addition of immobilized phosphates did not accelerate nanoceria dissolution, suggesting that the Ce3+ ion release during nanoceria dissolution was phosphate-independent. Smaller particles resulting from partial nanoceria dissolution led to less cellular protein carbonyl formation, attributed to an increased amount of surface Ce3+ species. Surface reactivity was greater for the solvothermally synthesized nanoceria, which had more Ce3+ species at the surface. The results show that temperature treatment of nanoceria can produce significant differences in solubility and surface cerium valence, which affect the biological and catalytic properties of nanoceria

2012 Annual Report - Advanced Biomedical Information Technology Core

This material is based upon work supported in part by the following funding agencies and grant awards: • Lilly Endowment, for its support of the Indiana Genomics Initiative (INGEN) – 2000; Indiana Metabolomics and Cytomics Initiative (METACyt); Indiana Pervasive Computing Research (IPCRES) initiative and Pervasive Technology Institute (1999 and 2008 respectively) • National Science Foundation under grants 01116050 MRI: Creation of the AVIDD Data Facility: A Distributed Facility for Managing, Analyzing and Visualizing Instrument-Driven Data (Michael A. McRobbie, PI); 0521433 MRI: Acquisition of a High-Speed, High Capacity Storage System to Support Scientific Computing: The Data Capacitor (Craig A. Stewart, PI); 0521433 ABI Development: National Center for Genome Analysis Support (Craig A. Stewart, PI) • National Institutes of Health NIAAA awards U24 AA014818-01 (Craig A. Stewart, PI) and U24 AA014818-04 (William K. Barnett, PI) Informatics Core for the Collaborative Initiative on Fetal Alcohol Spectrum Disorder • Subcontracts through the following NIH grant awards: 5P40RR024928 (Kenneth Cornetta, PI), 2U01AA014809 (Tatiana Foroud, PI), 1DP2OD007363-01 (Alexander Niculescu, PI), UL1RR025761-01 (Anantha Shekhar, PI), 3UL1RR025761-04S2 (Anantha Shekhar, PI), and 3UL1RR025761-04S3 (Anantha Shekhar, PI) • Funding from the general funds of Indiana University Any opinions expressed in this document are those of the authors and do not necessarily reflect the views of the funding agencies above