Development of new structural alerts suitable for chemical category formation for assigning covalent and non-covalent mechanisms relevant to DNA binding

The need to assess the ability of a chemical to act as a mutagen is one of the primary requirements in regulatory toxicology. Several pieces of legislation have led to an increased interest in the use of in silico methods, specifically the formation of chemical categories and read-across for the assessment of toxicological endpoints. One of the key steps in the development of chemical categories for mutagenicity is defining the mechanistic organic chemistry associated with the formation of a covalent bond between DNA and an exogenous chemical. To this end this study has analysed, by use of a large set of mutagenicity data (Ames test), the mechanistic coverage of a recently published set of in silico structural alerts developed for category formation. The results show that the majority of chemicals with a positive result in the Ames test were assigned at least one covalent binding mechanism related to the formation of a DNA adduct. The remaining chemicals with positive data in the Ames assay were subjected to a detailed mechanistic analysis from which 26 new structural alerts relating to covalent binding mechanisms were developed. In addition, structural alerts for radical and non-covalent intercalation mechanisms were also defined. The structural alerts outlined in this study are not intended to predict mutagenicity but rather to identify mechanisms associated with covalent and non-covalent DNA binding. This mechanistic profiling information can then be used to form chemical categories suitable for filling data gaps via read-across. A strategy for chemical category formation for mutagenicity is also presented.     

The influence of intraspecific competition on resource allocation during dependent colony foundation in a social insect

Organisms face a trade-off between investment in fewer, larger offspring, or more, smaller offspring. Most organisms can adjust investment through variation in the size and number of offspring in response to factors such as resource availability and competition. In some social animals, established colonies divide into groups of individuals that become autonomous, a process known as colony fission (also dependent colony foundation in social insects). Resource allocation under fission can be fine-tuned by adjusting the number of new groups (offspring number) and the number of individuals in each new group (offspring size). We assessed the influence of competition on resource allocation during fission in the ant Cataglyphis cursor, by allowing colonies to fission in experimental enclosures of high or low conspecific colony density. The pattern of colony fission was similar to that observed in the field: each fissioning colony produced a few new nests comprising a highly variable number of workers and a single queen, the old queen was often replaced, and new queens were produced in excess. The number of new nests produced depended on the available workforce in the parent colony but was not affected by differences in colony density. Comparison with data from fission under natural field conditions, however, indicates that colonies in enclosures produced fewer, larger new nests, suggesting that resource investment patterns during fission are indeed subject to extrinsic factors. The density of conspecific colonies in the immediate surroundings may be an unreliable estimate of competition intensity and other factors should be considered.     

Neighbouring chimpanzee communities show different preferences in social grooming behaviour

Grooming handclasp (GHC) behaviour was originally advocated as the first evidence of social culture in chimpanzees owing to the finding that some populations engaged in the behaviour and others do not. To date, however, the validity of this claim and the extent to which this social behaviour varies between groups is unclear. Here, we measured (i) variation, (ii) durability and (iii) expansion of the GHC behaviour in four chimpanzee communities that do not systematically differ in their genetic backgrounds and live in similar ecological environments. Ninety chimpanzees were studied for a total of 1029 h; 1394 GHC bouts were observed between 2010 and 2012. Critically, GHC style (defined by points of bodily contact) could be systematically linked to the chimpanzee''s group identity, showed temporal consistency both within and between groups, and could not be accounted for by the arm-length differential between partners. GHC has been part of the behavioural repertoire of the chimpanzees under study for more than 9 years (surpassing durability criterion) and spread across generations (surpassing expansion criterion). These results strongly indicate that chimpanzees'' social behaviour is not only motivated by innate predispositions and individual inclinations, but may also be partly cultural in nature.     

High strain rate compressive properties of bovine muscle tissue determined using a split Hopkinson bar apparatus

The polymeric split Hopkinson pressure bar (PSHPB) apparatus is introduced as a means for measuring the high strain rate (1,000-2,500 s(-1)) compressive properties of soft tissues. Issues related to specimen design are discussed, and protocols are presented for specimen preparation. Proposed specimen geometries were validated using high-speed photography. Stress-strain data were obtained for high strain rate compression of bovine muscle tissue to strains as high as 80%. The stress-strain curves were found to be strain rate-sensitive and concave upward, as is typical of soft tissues. Rigor had a significant impact on the material properties between 5 and 24 h post mortem, while at longer times, properties returned essentially to their pre-rigor values. This study presents some of the first published high rate properties of muscle tissue, data that are urgently for advanced modeling of the human body and for evaluation of safety systems for the human body.     

Influence of freshwater macrophytes on the littoral ecosystem structure and function of a young Colorado reservoir

The presence of rooted macrophytes, mostly the milfoil Myriophyllum sibiricum, was manipulated in enclosures in the littoral zone of a Colorado reservoir. The presence of macrophytes significantly increased the abundance of major invertebrate taxa by 70–1725% and increased the emission of methane 127%. The increase in abundance of most invertebrates was probably due to the habitat and surfaces provided by milfoil as stable isotope analyses indicated that milfoil was an insignificant carbon source for all of the invertebrate taxa, except for the milfoil midge Cricotopus myriophylli. Cricotopus is known to specialize on milfoil (other members of the genus specialize on Hydrilla or are generalists), had an isotopic signature that indicated a diet of milfoil, and was about 15 times more abundant when milfoil was present than when it was absent. Milfoil had no detectable effect on the total particulate phosphorus (TPP), soluble reactive phosphorus (SRP), total dissolved phosphorus (TDP), dissolved organic phosphorus (DOP), and Chl a of water within the enclosures. However, enclosures containing milfoil had higher concentrations of SRP in the pore water of surface sediments than enclosures that had milfoil removed. SRP in pore water dropped below 2 μg/L at >2 cm sediment depth and DOP increased progressively from nearly zero at the surface to about 150 μg/L at 15 cm depth, regardless of vegetation. Thus, milfoil had significant effects on many, but not all, measures of littoral ecosystem structure and function that were monitored.     

A review of the status of alternative approaches to animal testing and the development of integrated testing strategies for assessing the toxicity of chemicals under REACH--a summary of a DEFRA-funded project conducted by Liverpool John Moores University and FRAME

Liverpool John Moores University and FRAME were recently awarded a DEFRA tender to conduct a review of the status of alternative approaches to animal testing, and to recommend further research with regard to the forthcoming European Union REACH (Registration, Evaluation and Authorisation of Chemicals) system for the safety testing and risk assessment of chemicals. The outcome of the project is summarised, including the prospects for in vitro and in silico testing, areas where reduction and refinement could be applied, and how decision-tree integrated testing strategies could be used to reduce the number of animals needed to fulfil the testing requirements of the REACH system. This paper is a prelude to a series of individual papers on detailed suggestions for applying non-animal methods to each of the major toxicity endpoints in REACH.