Expression and function of the P2X7 receptor in human osteoblasts: The role of NFATc1 transcription factor

Bone mineralization is an orchestrated process by which mineral crystals are de- posited by osteoblasts; however, the detailed mechanisms remain to be elucidated. The presence of P2X7 receptor (P2X7R) in immature and mature bone cells is well established, but contrasting evidence on its role in osteogenic differentiation and deposition of calcified bone matrix remains. To clarify these controversies in the present study, we investigated P2X7R participation in bone maturation. We de- monstrated that the P2X7R is expressed and functional in human primary osteo- blasts, and identified in the P2RX7 promoter several binding sites for transcription factors involved in bone mineralization. Of particular interest was the finding that P2X7R expression is enhanced by nuclear factor of activated T cells cytoplasmic 1 (NFATc1) overexpression, and accordingly, NFATc1 is recruited at the P2RX7 gene promoter in SaOS2 osteoblastic like cells. In conclusion, our data provide further insights into the regulation of P2X7R expression and support the development of drugs targeting this receptor for the therapy of bone diseases

Integration of the biophysical and social sciences using an indicator approach: Addressing water problems at different scales

To be operationally sustainable, any system of environmental management needs to be based on a truly holistic assessment of all of the relevant factors influencing it. This is of course a daunting task, demanding as it does detailed and reliable data, not only from both the physical and social sciences, but also incorporating some representation of that part of knowledge which could be described as non-scientific. This could be said to include the uncertainties of market forces and political will, as well as traditional knowledge systems, and artistic representation. Recognising the limitations of our own knowledge system is important if we are to make progress in the achievement of sustainability. The development of less deterministic models is a step forward in that direction. This paper provides some discussion on the challenges associated with the integration of data from different disciplines, and the application of that data at different scales. Alternative approaches to the assessment of water resources for policy making are highlighted, and the validity of using such assessments at different scales is discussed. Using the Water Poverty Index as illustration, examples are provided of how an integrated assessment framework can be used to provide consistency and transparency in decision-making, and how this can, in practice, be applied at a variety of scales