Silica nanoparticles inhibit the cation channel TRPV4 in airway epithelial cells

Background

Silica nanoparticles (SiNPs) have numerous beneficial properties and are extensively used in cosmetics and food industries as anti-caking, densifying and hydrophobic agents. However, the increasing exposure levels experienced by the general population and the ability of SiNPs to penetrate cells and tissues have raised concerns about possible toxic effects of this material. Although SiNPs are known to affect the function of the airway epithelium, the molecular targets of these particles remain largely unknown. Given that SiNPs interact with the plasma membrane of epithelial cells we hypothesized that they may affect the function of Transient Receptor Potential Vanilloid 4 (TRPV4), a cation-permeable channel that regulates epithelial barrier function. The main aims of this study were to evaluate the effects of SiNPs on the activation of TRPV4 and to determine whether these alter the positive modulatory action of this channel on the ciliary beat frequency in airway epithelial cells.

Results

Using fluorometric measurements of intracellular Ca²⁺ concentration ([Ca²⁺]_i) we found that SiNPs inhibit activation of TRPV4 by the synthetic agonist GSK1016790A in cultured human airway epithelial cells 16HBE and in primary cultured mouse tracheobronchial epithelial cells. Inhibition of TRPV4 by SiNPs was confirmed in intracellular Ca²⁺ imaging and whole-cell patch-clamp experiments performed in HEK293T cells over-expressing this channel. In addition to these effects, SiNPs were found to induce a significant increase in basal [Ca²⁺]_i, but in a TRPV4-independent manner. SiNPs enhanced the activation of the capsaicin receptor TRPV1, demonstrating that these particles have a specific inhibitory action on TRPV4 activation. Finally, we found that SiNPs abrogate the increase in ciliary beat frequency induced by TRPV4 activation in mouse airway epithelial cells.

Conclusions

Our results show that SiNPs inhibit TRPV4 activation, and that this effect may impair the positive modulatory action of the stimulation of this channel on the ciliary function in airway epithelial cells. These findings unveil the cation channel TRPV4 as a primary molecular target of SiNPs.

     

PGRP-LB: An Inside View into the Mechanism of the Amidase Reaction

Peptidoglycan recognition proteins (PGRPs) are ubiquitous among animals and play pivotal functions in insect immunity. Non-catalytic PGRPs are involved in the activation of immune pathways by binding to the peptidoglycan (PGN), whereas amidase PGRPs are capable of cleaving the PGN into non-immunogenic compounds. Drosophila PGRP-LB belongs to the amidase PGRPs and downregulates the immune deficiency (IMD) pathway by cleaving meso-2,6-diaminopimelic (meso-DAP or DAP)-type PGN. While the recognition process is well analyzed for the non-catalytic PGRPs, little is known about the enzymatic mechanism for the amidase PGRPs, despite their essential function in immune homeostasis. Here, we analyzed the specific activity of different isoforms of Drosophila PGRP-LB towards various PGN substrates to understand their specificity and role in Drosophila immunity. We show that these isoforms have similar activity towards the different compounds. To analyze the mechanism of the amidase activity, we performed site directed mutagenesis and solved the X-ray structures of wild-type Drosophila PGRP-LB and its mutants, with one of these structures presenting a protein complexed with the tracheal cytotoxin (TCT), a muropeptide derived from the PGN. Only the Y78F mutation abolished the PGN cleavage while other mutations reduced the activity solely. Together, our findings suggest the dynamic role of the residue Y78 in the amidase mechanism by nucleophilic attack through a water molecule to the carbonyl group of the amide function destabilized by Zn²⁺.     

Thermal stability of NO 2 ⋅ and NO⋅ radicals formed in an Al23 catalyst during its preparation from a nitrate precursor

During the preparation of alumina as a catalyst support from aluminium nitrates by precipitation with a NH₄OH base, NO ₂ ^⋅ radicals have been formed in the catalyst after calcination under air in the solid at different temperatures. These radicals remained stable until a calcination temperature of 800°C. When the calcined catalyst was degassed under vacuum above 300 °C, the NO ₂ ^⋅ was reduced to give NO^⋅ and O^- species which were both tightly trapped in the solid. These latter species remained stable until vacuum treatment at 800 °C. This revised version was published online in July 2006 with corrections to the Cover Date.     

Effect of dietary lipid sources on odour‐active compounds in muscle of turbot (Psetta maxima)

Odour‐active compounds in muscle of turbot (Psetta maxima) fed experimental diets containing fish oil (FO), soybean oil (SO) or linseed oil (LO) were investigated by a gas chromatography/olfactometry technique. Thirty‐one areas associated with odours were detected in muscle extracts. Among the compounds responsible for these odours, 23 were formed by oxidation of unsaturated fatty acids. Independently of diet, (E)‐2‐penten‐1‐ol and (E)‐3‐hexen‐1‐ol contribute strongly to the odour of turbot. (E,Z)‐2,6‐Nonadienal, (E)‐2‐pentenal and (E,E)‐1,3‐(Z)‐5‐octatriene seem to contribute strongly to the odour of turbot fed diets containing high levels of n‐3 PUFA (FO and LO groups). Hexanal and decanal show a high detection frequency in turbot fed diets containing vegetable oils. Odorous compounds which are not formed by lipid oxidation (methional, 1‐acetyl pyrazine, 4‐ethyl benzaldehyde and 2‐acetyl‐2‐thiazoline) were not affected by dietary lipid sources. © 2001 Society of Chemical Industry     

Synthesis by Spark Plasma Sintering: A new way to obtain electrode materials for lithium ion batteries

In the search of high-performance materials for lithium ion batteries, Li₂CoPO₄F offers many advantages like high theoretical capacity and high operating potential. The synthesis of Li₂CoPO₄F has been reinvestigated considering a conventional solid state reaction and an unconventional way. Due to the long heat-treatments required by the conventional approach, a beginning of grains coalescence is observed. Limiting particles growth has been allowed by a shorter reaction done by SPS (Spark Plasma Sintering). By this method, the synthesis of Li₂CoPO₄F was greatly shortened (from 10 h to 9 min), which favours the getting of submicrometric particles. The comparison of the electrochemical properties of the Li₂CoPO₄F obtained by the different ways confirms the advantages of SPS synthesis in performance enhancement.     

Assessment of biogas potential hazards

Biogas produced from anaerobic fermentation of organic substances represents an alternative renewable energy source. Its utilization would contribute to substantial reduction of the solid waste volume in land-filling and incineration. Biogas so produced could be utilized on site or it could be injected into the natural gas distribution network. Microbiological and chemical compositions of different biogas types were determined in order to conduct qualitative and quantitative risk assessments of the potential health hazards associated with biogas use for cooking. Biogas types that could be allowed for injection in the natural gas pipelines were listed with recommendations, while outlining the European biogas injection policy. Results indicated that the injection of the processed biogas in the distribution network did not present any additional chemical or microbiological risk to consumers when compared to natural gas, provided that the biogas resulted from the fermentation of non-dangerous waste. However, since this study did not examine the microbiological and chemical composition of biogas originating from wastewater sludges and/or industrial wastes, the injection of this type of biogas into the gas distribution network should not be allowed unless a similar risk evaluation study is conducted for each case.     

A Semantic Web-Based Approach to Knowledge Management for Grid Applications

Knowledge has become increasingly important to support intelligent process automation and collaborative problem solving in large-scale science over the Internet. This paper addresses distributed knowledge management, its approach and methodology, in the context of grid application. We start by analyzing the nature of grid computing and its requirements for knowledge support; then, we discuss knowledge characteristics and the challenges for knowledge management on the grid. A semantic Web-based approach is proposed to tackle the six challenges of the knowledge lifecycle - namely, those of acquiring, modeling, retrieving, reusing, publishing, and maintaining knowledge. To facilitate the application of the approach, a systematic methodology is conceived and designed to provide a general implementation guideline. We use a real-world Grid application, the GEODISE project, as a case study in which the core semantic Web technologies such as ontologies, semantic enrichment, and semantic reasoning are used for knowledge engineering and management. The case study has been fully implemented and deployed through which the evaluation and validation for the approach and methodology have been performed     

Identity ambiguity and the promises and practices of hybrid e-HRM project teams

The role of IS project team identity work in the enactment of day-to-day relationships with their internal clients is under-researched. We address this gap by examining the identity work undertaken by an electronic human resource management (e-HRM) ‘hybrid’ project team engaged in an enterprise-wide IS implementation for their multi-national organisation. Utilising social identity theory, we identify three distinctive, interrelated dimensions of project team identity work (project team management, team ‘value propositions’ (promises) and the team’s ‘knowledge practice’). We reveal how dissonance between two perspectives of e-HRM project identity work (clients’ expected norms of project team’s service and project team’s expected norms of themselves) results in identity ambiguity. Our research contributions are to identity studies in the IS project management, HR and hybrid literatures and to managerial practice by challenging the assumption that hybrid experts are the panacea for problems associated with IS projects.     

Biosynthesis of polyunsaturated fatty acids in the developing brain: II. Metabolic transformations of intracranially administered [3-14C] eicosatrienoic acid,evidence for lack of Δ8 desaturasedesaturase

[3-¹⁴C] Eicosatrienoic acid (Δ11,14,17) chemically synthesized from [1-¹⁴C] linolenic acid was injected intracranially into 14-day old rats and sacrificed 8 hr later. The analysis of brain fatty acids by radio-gas liquid chromatography before and after ozonolysis showed that the tetraene fraction consisted of a desaturated product, Δ5,11,17–20∶4, and its elongated product, Δ7,13,16,19–22∶4. Both of these products, with a combined total of 61% of the total radioactivity recovered in the tetraene fraction, contain a nonmethylene interrupted double bond system and, therefore, are unsuitable for further desaturation. The other two components, Δ6,9,12,15–18∶4 and Δ8,11,14,17–20∶4, must have been formed from Δ9,12,15–18∶3, formed by retroconversion of the starting material 20∶3, followed by desaturation and elongation. These results suggest a lack of Δ⁸ desaturase in the developing brain, leading to formation of Δ5,11,14,17–20∶4 rather than Δ8,11,14,17–20∶4. Howeve, the nonmethylene interrupted double bond isomer does not restrict chain elongation.     

Clinical and Molecular Characterization of Patients with Mucopolysaccharidosis Type I in an Algerian Series

Mucopolysaccharidoses (MPS’s) represent a subgroup of lysosomal storage diseases related to a deficiency of enzymes that catalyze glycosaminoglycans degradation. Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder caused by a deficiency of α-l-iduronidase encoded by the IDUA gene. Partially degraded heparan sulfate and dermatan sulfate accumulate progressively and lead to multiorgan dysfunction and damage. The aim of this study is to describe the clinical, biochemical, and molecular characteristics of 13 Algerian patients from 11 distinct families. MPS I diagnosis was confirmed by molecular study of the patients’ IDUA gene. Clinical features at the diagnosis and during the follow-up are reported. Eighty-four percent of the studied patients presented with a mild clinical phenotype. Molecular study of the IDUA gene allowed the characterization of four pathological variations at the homozygous or compound heterozygote status: IDUA NM_00203.4:c.1598C>G-p.(Pro533Arg) in 21/26 alleles, IDUA NM_00203.4:c.532G>A-p.(Glu178Lys) in 2/26 alleles, IDUA NM_00203.4:c.501C>G-p.(Tyr167*) in 2/26 alleles, and IDUA NM_00203. 4: c.1743C>G-p.(Tyr581*) in 1/26 alleles. This molecular study unveils the predominance of p.(Pro533Arg) variation in our MPS I patients. In this series, the occurrence of some clinical features linked to the Scheie syndrome is consistent with the literature, such as systematic valvulopathies, corneal opacity, and umbilical hernia; however, storage signs, facial dysmorphic features, and hepatomegaly were more frequent in our series. Screening measures for these debilitating diseases in highly consanguineous at-risk populations must be considered a priority health problem.