Key challenges facing data-driven multicellular systems biology

Increasingly sophisticated experiments, coupled with large-scale computational models, have the potential to systematically test biological hypotheses to drive our understanding of multicellular systems. In this short review, we explore key challenges that must be overcome to achieve robust, repeatable data-driven multicellular systems biology. If these challenges can be solved, we can grow beyond the current state of isolated tools and datasets to a community-driven ecosystem of interoperable data, software utilities, and computational modeling platforms. Progress is within our grasp, but it will take community (and financial) commitment

Understanding Concerns about Community Relations in Calderdale

•This study examined attitudes and dispositions towards greater ethnic and religious diversity, as well as community relations more generally, among residents of predominantly white British neighbourhoods. It also examined people’s attitudes and responses to anti-minority protest by groups like the English Defence League (EDL)and towards cohesion policy and practices. A mixed methods design was used combining a (non-representative) household survey (n=212) in three selected research sites (Illingworth, Sowerby Bridge and Todmorden) with eight key informant interviews (across key institutions) and nine focus group discussions (across age-ranges and localities) with local people

Understanding Concerns about Community Relations in Kirklees

This study examined attitudes and dispositions towards greater ethnic and religious diversity, as well as community relations more generally, among residents of predominantly white British neighbourhoods. It also examined people’s attitudes and responses to anti-minority protest by groups like the English Defence League (EDL) and towards cohesion policy and practices. A mixed methods design was used combining a (non-representative) household survey (n=434) in four selected research sites (three areas in north Kirklees, one area in south Kirklees) with six key informant interviews (across key institutions) and fifteen focus group discussions (across age-ranges and localities) with local peopl

An agent-based model for elasto-plastic mechanical interactions between cells, basement membrane and extracellular matrix

The basement membrane (BM) and extracellular matrix (ECM) play critical roles in developmental and cancer biology, and are of great interest in biomathematics. We introduce a model of mechanical cell-BM-ECM interactions that extends current (visco)elastic models (e.g. [8, 16]), and connects to recent agent-based cell models (e.g. [2, 3, 20, 26]). We model the BM as a linked series of Hookean springs, each with time-varying length, thickness, and spring constant. Each BM spring node exchanges adhesive and repulsive forces with the cell agents using potential functions. We model elastic BM-ECM interactions with analogous ECM springs. We introduce a new model of plastic BM and ECM reorganization in response to prolonged strains, and new constitutive relations that incorporate molecular-scale effects of plasticity into the spring constants. We find that varying the balance of BM and ECM elasticity alters the node spacing along cell boundaries, yielding a nonuniform BM thickness. Uneven node spacing generates stresses that are relieved by plasticity over long times. We find that elasto-viscoplastic cell shape response is critical to relieving uneven stresses in the BM. Our modeling advances and results highlight the importance of rigorously modeling of cell-BM-ECM interactions in clinically important conditions with signicant membrane deformations and time-varying membrane properties, such as aneurysms and progression from in situ to invasive carcinoma

Isotopic provenancing of Pb in Mitrovica, northern Kosovo: source identification of chronic Pb enrichment in soils, house dust and scalp hair

Mitrovica, northern Kosovo, is the site of some of the highest Pb concentrations reported in human populations; exemplified by Pb concentrations in scalp hair of up to 130 μg g-1 and widely-publicized of Pb-related ill-health and mortality amongst internally displaced populations. High human Pb burdens are accompanied by elevated concentrations of potentially harmful elements (PHEs) in soils and house dust within the city, which has a long history of mining and metallurgy. In this study enrichment-levels for PHEs in soils are quantified and compared to environmental quality guidelines and a statistically-derived estimation of background concentration. In addition, Pb isotopes (207Pb/206Pb, 208Pb/206Pb) are used to characterise the isotopic signatures of potential point sources of Pb and a mixing model employed to quantify the contribution of sources to Pb present in soils, house dust, and the scalp hair of children and young people. Pb isotopic evidence suggests that Pb in surface soils and house-dust is predominantly sourced from historical deposition of Pb-containing aerosols from metal smelting, with lower contributions from wind-blown dispersal of metalliferous waste. Pb present in scalp hair is interpreted as the result of non-occupational exposure and the ingestion and/or inhalation of Pb-enriched surface soil and house dust. This study represents one of the very few instances where this type of geochemical tracing technique has been successfully applied to definitively identify the source of Pb present within biological samples. The results of this study are of particular relevance to environmental management and highlight the human health risk posed by the legacy of now inactive mining and metallurgy in addition to the challenge posed in mitigating the risk posed by diffuse soil pollution. © 2015 Elsevier Ltd