A simplified model of scar contraction

The healing of wounds is a complex process and the contraction of the resulting scar can have a negative impact on the neighbouring skin. A finite element model of skin simulating the contraction of a scar and deformation of the surrounding skin is presented. The skin is represented by an orthotropic–viscoelastic constitutive law, which is validated against experimental data in the literature. A simplified experimental model of a contracting scar in real skin is also developed. The pattern and size of the wrinkles formed around the contracting scar in the finite element model compare favourably with those formed in the experimental model. The orthotropic nature of skin plays a significant role in the behaviour of skin around scars—the wrinkles have a preferential orientation that corresponds to a direction perpendicular to the Langer's lines in the skin. The pre-stress in skin (a property that is ignored in many skin models) is shown to be an important factor in wrinkle formation around scars. The proposed model can be used to analyse the suturing and closure of wounds of various shapes.     

Novel phenotypes identified by plasma biochemical screening in the mouse

We used ENU mutagenesis in the mouse for the rapid generation of novel mutant phenotypes for both gene function studies and use as new animal models of human disease (Nolan et al. 2000b). One focus of the program was the development of a blood biochemistry screen. At 8-12 weeks of age, approximately 300 ml of blood was collected from F1 offspring of ENU mutagenized male mice. This yielded approximately 125 ml of plasma, used to perform a profile of 17 standard biochemical tests on an Olympus analyzer. Cohorts of F1 mice were also aged and then retested to detect late onset phenotypes. In total, 1,961 F1s were screened. Outliers were identified by running means and standard deviations. Of 70 mice showing consistent abnormalities in plasma biochemistry, 29 were entered into inheritance testing. Of these, 9 phenotypes were confirmed as inherited, 10 found not to be inherited, and 10 are still being tested. Inherited mutant phenotypes include abnormal lipid profiles (low total and HDL cholesterol, high triglycerides); abnormalities in bone and liver metabolism (low ALP, high ALP, high ALT, and AST); abnormal plasma electrolyte levels (high sodium and chloride); as well as phenotypes of interest for the study of diabetes (high glucose). The gene loci bearing the mutations are currently being mapped and further characterized. Our results have validated our biochemical screen, which is applicable to other mutagenesis projects, and we have produced a new set of mutants with defined metabolic phenotypes.     

Mouse splenic macrophage cell lines with different antigen-presenting activities for CD4+ helper T cell subsets and allogeneic CD8+ T cells.

A panel of seven mouse splenic macrophage cell lines, derived from cloned progenitors, was compared for their ability to present antigen to Th1 or Th2 helper T cell lines and hybridomas, as well as to naive T cells, and to provide accessory cell function for the synthesis of antibody from primed B cells. One of the cell lines expressed MHC class II molecules and was the only line with constitutive antigen-presenting activity for Th1 cells. It may represent a subset of splenic macrophages responsible for the activation of naive Th1 helper cells in situ. The remaining six cell lines responded to INF-gamma by up-regulating their class II expression and acquiring Th1 antigen-presenting activity. They may represent cells which, in situ, lack constitutive antigen-presenting activity but are promoted to presenting status by Th1-derived INF-gamma. Five of the cell lines provided accessory cell function to Th2 cells, as indicated by antibody synthesis in suspensions of spleen cells from primed mice depleted of their antigen-presenting cells. One of the cell lines lacking accessory cell activity had constitutive antigen-presenting activity for Th1 cells. This reciprocal expression of antigen-presenting activity supports the idea that Th1 and Th2 helper cells are activated by different antigen-presenting cells. Finally, the cell lines differed in their ability to constitutively induce an allogeneic response; a response that was limited to CD8+ T cells occurred in a CD4+ helper cell-independent manner and was unaffected by the addition of INF-gamma. The alloantigen-presenting macrophage cell lines also possessed the most efficient accessory cell activity for antibody synthesis. These cell lines, which represent a spectrum of antigen-presenting activities in the spleen afford models for defining the roles of macrophages in the induction of immune responses and for resolving issues concerning their development.     

What works in conservation? Using expert assessment of summarised evidence to identify practices that enhance natural pest control in agriculture

This paper documents an exercise to synthesize and assess the best available scientific knowledge on the effectiveness of different farm practices at enhancing natural pest regulation in agriculture. It demonstrates a novel combination of three approaches to evidence synthesis—systematic literature search, collated synopsis and evidence assessment using an expert panel. These approaches follow a logical sequence moving from a large volume of disparate evidence to a simple, easily understandable answer for use in policy or practice. The example of natural pest regulation in agriculture was selected as a case study within two independent science-policy interface projects, one European and one British. A third funder, a private business, supported the final stage to translate the synthesized findings into a useful, simplified output for agronomists. As a whole, the case study showcases how a network of scientific knowledge holders and knowledge users can work together to improve the use of science in policy and practice. The process identified five practices with good evidence of a benefit to natural pest regulation, with the most beneficial being ‘Combine trap and repellent crops in a push–pull system’. It highlights knowledge gaps, or potential research priorities, by showing practices considered important by stakeholders for which there is not enough evidence to make an assessment of effects on natural pest regulation, including ‘Alter the timing of pesticide application.’ Finally, the process identifies several important practices where the volume of evidence of effects on natural pest regulation was too large (>300 experimental studies) to be summarised with the resources available, and for which focused systematic reviews may be the best approach. These very well studied practices include ‘Reduce tillage’ and ‘Plant more than one crop per field’.     

Influence of physical activity on tibial bone material properties in laying hens

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as cortical and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. These differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.