A vision of the future for BMC Medicine: serving science, medicine and authors

In June 2009, BMC Medicine received its first official impact factor of 3.28 from Thomson Reuters. In recognition of this landmark event, the BMC Medicine editorial team present and discuss the vision and aims of the journal

Stochastic loss and gain of symmetric divisions in the C. elegans epidermis perturbs robustness of stem cell number

Biological systems are subject to inherent stochasticity. Nevertheless, development is remarkably robust, ensuring the consistency of key phenotypic traits such as correct cell numbers in a certain tissue. It is currently unclear which genes modulate phenotypic variability, what their relationship is to core components of developmental gene networks, and what is the developmental basis of variable phenotypes. Here, we start addressing these questions using the robust number of Caenorhabditis elegans epidermal stem cells, known as seam cells, as a readout. We employ genetics, cell lineage tracing, and single molecule imaging to show that mutations in lin-22, a Hes-related basic helix-loop-helix (bHLH) transcription factor, increase seam cell number variability. We show that the increase in phenotypic variability is due to stochastic conversion of normally symmetric cell divisions to asymmetric and vice versa during development, which affect the terminal seam cell number in opposing directions. We demonstrate that LIN-22 acts within the epidermal gene network to antagonise the Wnt signalling pathway. However, lin-22 mutants exhibit cell-to-cell variability in Wnt pathway activation, which correlates with and may drive phenotypic variability. Our study demonstrates the feasibility to study phenotypic trait variance in tractable model organisms using unbiased mutagenesis screens

Residual photosensitivity in mice lacking both rod opsin and cone photoreceptor cyclic nucleotide gated channel 3 alpha subunit

The mammalian retina contains three classes of photoreceptor. In addition to the rods and cones, a subset of retinal ganglion cells that express the putative sensory photopigment melanopsin are intrinsically photosensitive. Functional and anatomical studies suggest that these inner retinal photoreceptors provide light information for a number of non-image-forming light responses including photoentrainment of the circadian clock and the pupil light reflex. Here, we employ a newly developed mouse model bearing lesions of both rod and cone phototransduction cascades (Rho-/- Cnga3-/-) to further examine the function of these non-rod non-cone photoreceptors. Calcium imaging confirms the presence of inner retinal photoreceptors in Rho-/- Cnga3-/- mice. Moreover, these animals retain a pupil light reflex, photoentrainment, and light induction of the immediate early gene c-fos in the suprachiasmatic nuclei, consistent with previous findings that pupillary and circadian responses can employ inner retinal photoreceptors. Rho-/- Cnga3-/- mice also show a light-dependent increase in the number of FOS-positive cells in both the ganglion cell and (particularly) inner nuclear layers of the retina. The average number of cells affected is several times greater than the number of melanopsin-positive cells in the mouse retina, suggesting functional intercellular connections from these inner retinal photoreceptors within the retina. Finally, however, while we show that wild types exhibit an increase in heart rate upon light exposure, this response is absent in Rho-/- Cnga3-/- mice. Thus, it seems that non-rod non-cone photoreceptors can drive many, but not all, non-image-forming light responses

Participatory adaptation planning and costing. Applications in agricultural adaptation in Western Kenya

Adaptation to climate change is an important theme in the strategy and policy of institutions around the world. Billions of dollars are allocated every year, based on cost estimates of actions to cope with, or benefit from the impacts of climate change. Costing adaptation, however, is complex, involving multiple actors with differing values and a spectrum of possible adaptation strategies and pathways. Currently, expert driven, top-down approaches dominate adaptation costing in practice. These approaches are subject to misallocation, with global funds not always reaching vulnerable communities in most need. This paper introduces an analytical framework called Participatory Social Return on Investment (PSROI), which provides a structured framework for multi-stakeholder planning, selection and valuation of appropriate methods of adaptation. The broader economic, social and environmental impacts of these adaptation actions are explored and valued through a participatory process. PSROI is strength-based, building local capacity and generating stakeholder buy-in. The financial valuation generated provides an additional tool for examining and prioritizing adaptation actions based on their impact. Results from a pilot of the PSROI framework in a smallholder farming community in Western Kenya provide empirical evidence for the difference between expert driven desk-based and ground-based cost estimates that involve local communities. There was an approximate 70 % reduction in the valuation of an agroforestry intervention, selected by the local community, when compared between the desk-based valuation and that of the local community, using primary field data. This reduced expectation of the desk-based PSROI is justified by coherent explanations such as lack of knowledge about the intervention, misconception about the potential costs and benefits, and the risk-averse nature of the farmers. These and other important insights are fundamental for planning and decision-making, as well as appropriate targeting and delivery of funding for adaptation.Abrar S. Chaudhury, Ariella Helfgott, Thomas F. Thornton, Chase Sov