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Background Little is known concerning the function of inositol 1,4,5-triphosphate receptors (IP3Rs) in the adult heart experimentally. Moreover, whether these Ca2+ release channels are present and play a critical role in human cardiomyocytes remains to be defined. IP3Rs may be activated following Gαq-protein-coupled receptors (GPCR) stimulation affecting Ca2+ cycling, enhancing myocyte performance and, potentially, favoring an increase in the incidence of arrhythmias. Methods and Results IP3R function was determined in human left ventricular (LV) myocytes and this analysis was integrated with assays in mouse myocytes to identify the mechanisms by which IP3Rs influence the electrical and mechanical properties of the myocardium. We report that IP3Rs are expressed and operative in human LV myocytes. Following GPCR activation, Ca2+ mobilized from the sarcoplasmic reticulum via IP3Rs contributes to the decrease in resting membrane potential, prolongation of the action-potential, and occurrence of early after-depolarizations. Ca2+ transient amplitude and cell shortening are enhanced, and extra-systolic and dysregulated Ca2+ elevations and contractions become apparent. These alterations in the electromechanical behavior of human cardiomyocytes are coupled with increased isometric twitch of the myocardium and arrhythmic events, suggesting that GPCR activation provide inotropic reserve, which is hampered by electrical instability and contractile abnormalities. Additionally, our findings support the notion that increases in Ca2+ load by IP3Rs promote Ca2+ extrusion by forward mode Na+/Ca2+ exchange, an important mechanism of arrhythmic events. Conclusions Thus, the GPCR/IP3R axis modulates the electromechanical properties of the human myocardium and its propensity to develop arrhythmias.

As we watched the growing excitement and hype around the human genome project, we at the BMJ had a vision of the Oscar ceremonies. The scientists are in their tuxedos and sparkling dresses, slapping each other on the back, slurping champagne, and making extravagant, tearful speeches. Our readers are like the silent army of cleaners waiting outside: once the scientists have moved on to the next (postgenomic) party, they'll come in and start cleaning.

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This article discusses the relationship between a deconstructivist method in science and technology studies (STS) and the more recent moves towards a reconstructivist engagement with science and science policy making.Drawing on examples from the author's own research, the article identifies three forms of engagement and their relative utility and limitations. The article argues that these are typical of STS work that seeks direct engagement with science policy making and which could form the basis for a more "serviceable STS" that retains its critical and independent perspective on science. The paper concludes by arguing that the analysis has important implications for the ways in which STS expertise can articulate with science policy making.

Mesenchymal stem cells (MSCs) are in development for many clinical indications, based both on ‘stem’ properties (tissue repair or regeneration) and on signaling repertoire (immunomodulatory and anti-inflammatory effects). Potential conflation of MSC properties with those of tissue-derived stromal cells presents difficulties in comparing study outcomes and represents a source of confusion in cell therapy development. Cultured MSCs demonstrate significant heterogeneity in clonogenicity and multi-lineage differentiation potential. However in vivo biology of MSCs includes native functions unrelated to regenerative medicine applications, so do nomenclature and heterogeneity matter? In this perspective we examine some consequences of the nomenclature debate and heterogeneity of MSCs. Regulatory expectations are considered, emphasizing that product development should prioritize detailed characterization of therapeutic cell populations for specific indications.

This paper explores the impact of a new IT system on the knowledge claims and occupational boundaries made by professional groups within a hospital laboratory setting. Within organizational settings professional groups enjoy considerable power and status through the specialised knowledge claims they make, deploying a variety of material and discursive resources to secure these. However, when organizations introduce new technologies to manage information needs, professional boundaries and claims to expertise may be threatened. This paper examines the strategies deployed by two key professional groups -Medical Laboratory Scientific Officers and medics -to secure their knowledge claims and statuses within the new organizational context shaped in part by an IT system. Though medics were more successful here, they had to accommodate to new demands within the organization. The professional identity and organizational space of the MLSOs were also redefined but, in contrast, by being narrowed. The different experiences and strategies of the two groups reflect their unequal holding of cultural capital and their differential capacity to define their status relative to the organization itself

This article discusses the emergence of a patenting culture in university science. Patenting culture is examined empirically in the context of the increasing commercialization of science, and theoretically within debates over scientific "credibility. " The article explores the translation of academic credit into patents, and vice versa, and argues that this process raises new questions for our understanding of scientific recognition and of scientists' networks. In particular, the analysis suggests that scientists must move between two distinct social worlds to manage the rewards that academic and patent cultures carry.