Genotoxicity of inorganic mercury salts based on disturbed microtubule function

This study investigated the hypothesis that the chromosomal genotoxicity of inorganic mercury results from interaction(s) with cytoskeletal proteins. Effects of Hg2+ salts on functional activities of tubulin and kinesin were investigated by determining tubulin assembly and kinesin-driven motility in cell-free systems. Hg2+ inhibits microtubule assembly at concentrations above 1 μM, and inhibition is complete at about 10 μM. In this range, the tubulin assembly is fully (up to 6 μM) or partially (∼6-10 μM) reversible. The inhibition of tubulin assembly by mercury is independent of the anion, chloride or nitrate. The no-observed-effect- concentration for inhibition of microtubule assembly in vitro was 1 μM Hg2+, the IC50 5.8 μM. Mercury(II) salts at the IC 50 concentrations partly inhibiting tubulin assembly did not cause the formation of aberrant microtubule structures. Effects of mercury salts on the functionality of the microtubule motility apparatus were studied with the motor protein kinesin. By using a "gliding assay" mimicking intracellular movement and transport processes in vitro, HgCl2 affected the gliding velocity of paclitaxel-stabilised microtubules in a clear dose-dependent manner. An apparent effect is detected at a concentration of 0.1 μM and a complete inhibition is reached at 1 μM. Cytotoxicity of mercury chloride was studied in V79 cells using neutral red uptake, showing an influence above 17 μM HgCl2. Between 15 and 20 μM HgCl2 there was a steep increase in cell toxicity. Both mercury chloride and mercury nitrate induced micronuclei concentration-dependently, starting at concentrations above 0.01 μM. CREST analyses on micronuclei formation in V79 cells demonstrated both clastogenic (CREST-negative) and aneugenic effects of Hg2+, with some preponderance of aneugenicity. A morphological effect of high Hg2+ concentrations (100 μM HgCl2) on the microtubule cytoskeleton was verified in V79 cells by immuno-fluorescence staining. The overall data are consistent with the concept that the chromosomal genotoxicity could be due to interaction of Hg2+ with the motor protein kinesin mediating cellular transport processes. Interactions of Hg 2+ with the tubulin shown by in vitro investigations could also partly influence intracellular microtubule functions leading, together with the effects on the kinesin, to an impaired chromosome distribution as shown by the micronucleus test.

Determination of glutathione transferase (GSTT1-1) activities in different tissues based on formation of radioactive metabolites using 35S-glutathione

A new system has been developed to determine enzyme activities of glutathione transferase θ (GSTT1-1) based on radiometric product detection resulting from the enzymic reaction of methyl chloride with 35S-labelled glutathione. In principle, the method is universally applicable for determination of glutathione transferase activities towards a multiplicity of substrates. The method distinguishes between erythrocyte GSTT1-1 activities of human 'non-conjugators', 'low conjugators' and 'high conjugators'. Application to cytosol preparations of livers and kidneys of male and female Fischer 344 and B6C3F1 mice reveals differential GSTT1-1 activities in hepatic and renal tissues. These ought to be considered in species-specific modellings of organ toxicities of chlorinated hydrocarbons.

Species differences in acrylonitrile metabolism and toxicity between experimental animals and humans based on observations in human accidental poisonings

The high acute toxicity of acrylonitrile may be a result of its intrinsic biological reactivity or of its metabolite cyanide. Intravenous N-acetylcysteine has been recommended for treatment of accidental intoxications in acrylonitrile workers, but such recommendations vary internationally. Acrylonitrile is metabolized in humans and experimental animals via two competing pathways; the glutathione-dependent pathway is considered to represent an avenue of detoxication whilst the oxidative pathway leads to a genotoxic epoxide, cyanoethylene oxide, and to elimination of cyanide. Cases of acute acrylonitrile overexposure or intoxication have occurred within persons having industrial contact with acrylonitrile; the route of exposure was by inhalation and/or by skin contact. The combined observations lead to the conclusion of a much higher impact of the oxidative metabolism of acrylonitrile in humans than in rodents. This is confirmed by differences in the clinical picture of acute life-threatening intoxications in both species, as well as by differential efficacies of antidotes. A combination of N-acetylcysteine with sodium thiosulfate seems an appropriate measure for antidote therapy of acute acrylonitrile intoxications. Clinical observations also highlight the practical importance of human individual susceptibility differences. Furthermore, differential adduct monitoring, assessing protein adducts with different rates of decay, enables the development of more elaborated biological monitoring strategies for the surveillance of workers with potential acrylonitrile contact.

Porohyperelastic finite element model for the kangaroo humeral head cartilage based on experimental study and the consolidation theory

Solid-extracellular fluid interaction is believed to play an important role in the strain-rate dependent mechanical behaviors of shoulder articular cartilages. It is believed that the kangaroo shoulder joint is anatomically and biomechanically similar to human shoulder joint and it is easy to get in Australia. Therefore, the kangaroo humeral head cartilage was used as the suitable tissue for the study in this paper. Indentation tests from quasi-static (10-4/sec) to moderately high strain-rate (10-2/sec) on kangaroo humeral head cartilage tissues were conduced to investigate the strain-rate dependent behaviors. A finite element (FE) model was then developed, in which cartilage was conceptualized as a porous solid matrix filled with incompressible fluids. In this model, the solid matrix was modeled as an isotropic hyperelastic material and the percolating fluid follows Darcy’s law. Using inverse FE procedure, the constitutive parameters related to stiffness, compressibility of the solid matrix and permeability were obtained from the experimental results. The effect of solid-extracellular fluid interaction and drag force (the resistance to fluid movement) on strain-rate dependent behavior was investigated by comparing the influence of constant, strain dependent and strain-rate dependent permeability on FE model prediction. The newly developed porohyperelastic cartilage model with the inclusion of strain-rate dependent permeability was found to be able to predict the strain-rate dependent behaviors of cartilages.

Developing a transdisciplinary approach to improve urban traffic congestion based on Product Ecosystem theory

Product Ecosystem theory is an emerging theory that shows that disruptive “game changing” innovation is only possible when the entire ecosystem is considered. When environmental variables change faster than products or services can adapt, disruptive innovation is required to keep pace. This has many parallels with natural ecosystems where species that cannot keep up with changes to the environment will struggle or become extinct. In this case the environment is the city, the environmental pressures are pollution and congestion, the product is the car and the product ecosystem is comprised of roads, bridges, traffic lights, legislation, refuelling facilities etc. Each one of these components is the responsibility of a different organisation and so any change that affects the whole ecosystem requires a transdisciplinary approach. As a simple example, cars that communicate wirelessly with traffic lights are only of value if wireless-enabled traffic lights exist and vice versa. Cars that drive themselves are technically possible but legislation in most places doesn’t allow their use. According to innovation theory, incremental innovation tends to chase ever diminishing returns and becomes increasingly unable to tackle the “big issues.” Eventually “game changing” disruptive innovation comes along and solves the “big issues” and/or provides new opportunities. Seen through this lens, the environmental pressures of urban traffic congestion and pollution are the “big issues.” It can be argued that the design of cars and the other components of the product ecosystem follow an incremental innovation approach. That is why the “big issues” remain unresolved. This paper explores the problems of pollution and congestion in urban environments from a Product Ecosystem perspective. From this a strategy will be proposed for a transdisciplinary approach to develop and implement solutions.

Score-level multibiometric fusion based on Dempster-Shafer theory incorporating uncertainty factors

While existing multi-biometic Dempster-Shafer the- ory fusion approaches have demonstrated promising perfor- mance, they do not model the uncertainty appropriately, sug- gesting that further improvement can be achieved. This research seeks to develop a unified framework for multimodal biometric fusion to take advantage of the uncertainty concept of Dempster- Shafer theory, improving the performance of multi-biometric authentication systems. Modeling uncertainty as a function of uncertainty factors affecting the recognition performance of the biometric systems helps to address the uncertainty of the data and the confidence of the fusion outcome. A weighted combination of quality measures and classifiers performance (Equal Error Rate) are proposed to encode the uncertainty concept to improve the fusion. We also found that quality measures contribute unequally to the recognition performance, thus selecting only significant factors and fusing them with a Dempster-Shafer approach to generate an overall quality score play an important role in the success of uncertainty modeling. The proposed approach achieved a competitive performance (approximate 1% EER) in comparison with other Dempster-Shafer based approaches and other conventional fusion approaches.

A novel manoeuvering model based on low-aspect-ratio lift theory and Lagrangian mechanics

This paper proposes a physically motivated reappraisal of manoeuvring models for ships and presents a new model developed from first principles by application of low aspect-ratio aerodynamic theory and Lagrangian mechanics. The coefficients of the model are shown to be related to physical processes, and validation is presented using the results from a planar motion mechanism dataset.

Co-movements in commodity prices : a note based on network analysis

This article analyses co-movements in a wide group of commodity prices during the time period 1992–2010. Our methodological approach is based on the correlation matrix and the networks inside. Through this approach we are able to summarize global interaction and interdependence, capturing the existing heterogeneity in the degrees of synchronization between commodity prices. Our results produce two main findings: (a) we do not observe a persistent increase in the degree of co-movement of the commodity prices in our time sample, however from mid-2008 to the end of 2009 co-movements almost doubled when compared with the average correlation; (b) we observe three groups of commodities which have exhibited similar price dynamics (metals, oil and grains, and oilseeds) and which have increased their degree of co-movement during the sampled period.

Synonymization of key pest species within the Bactrocera dorsalis species complex (Diptera: Tephritidae): Taxonomic changes based on a review of 20 years of integrative morphological, molecular, cytogenetic, behavioural and chemoecological data

Bactrocera papayae Drew & Hancock, Bactrocera philippinensis Drew & Hancock, Bactrocera carambolae Drew & Hancock, and Bactrocera invadens Drew, Tsuruta & White are four horticultural pest tephritid fruit fly species that are highly similar, morphologically and genetically, to the destructive pest, the Oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae). This similarity has rendered the discovery of reliable diagnostic characters problematic, which, in view of the economic importance of these taxa and the international trade implications, has resulted in ongoing difficulties for many areas of plant protection and food security. Consequently, a major international collaborative and integrated multidisciplinary research effort was initiated in 2009 to build upon existing literature with the specific aim of resolving biological species limits among B. papayae, B. philippinensis, B. carambolae, B. invadens and B. dorsalis to overcome constraints to pest management and international trade. Bactrocera philippinensis has recently been synonymized with B. papayae as a result of this initiative and this review corroborates that finding; however, the other names remain in use. While consistent characters have been found to reliably distinguish B. carambolae from B. dorsalis, B. invadens and B. papayae, no such characters have been found to differentiate the latter three putative species. We conclude that B. carambolae is a valid species and that the remaining taxa, B. dorsalis, B. invadens and B. papayae, represent the same species. Thus, we consider B. dorsalis (Hendel) as the senior synonym of B. papayae Drew and Hancock syn.n. and B. invadens Drew, Tsuruta & White syn.n. A redescription of B. dorsalis is provided. Given the agricultural importance of B. dorsalis, this taxonomic decision will have significant global plant biosecurity implications, affecting pest management, quarantine, international trade, postharvest treatment and basic research. Throughout the paper, we emphasize the value of independent and multidisciplinary tools in delimiting species, particularly in complicated cases involving morphologically cryptic taxa.