Activated Met Signalling in the Developing Mouse Heart Leads to Cardiac Disease

BACKGROUND: The Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine involved in many physiological processes, including skeletal muscle, placenta and liver development. Little is known about its role and that of Met tyrosine kinase receptor in cardiac development. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we generated two transgenic mice with cardiac-specific, tetracycline-suppressible expression of either Hepatocyte Growth Factor (HGF) or the constitutively activated Tpr-Met kinase to explore: i) the effect of stimulation of the endogenous Met receptor by autocrine production of HGF and ii) the consequence of sustained activation of Met signalling in the heart. We first showed that Met is present in the neonatal cardiomyocytes and is responsive to exogenous HGF. Exogenous HGF starting from prenatal stage enhanced cardiac proliferation and reduced sarcomeric proteins and Connexin43 (Cx43) in newborn mice. As adults, these transgenics developed systolic contractile dysfunction. Conversely, prenatal Tpr-Met expression was lethal after birth. Inducing Tpr-Met expression during postnatal life caused early-onset heart failure, characterized by decreased Cx43, upregulation of fetal genes and hypertrophy. CONCLUSIONS/SIGNIFICANCE: Taken together, our data show that excessive activation of the HGF/Met system in development may result in cardiac damage and suggest that Met signalling may be implicated in the pathogenesis of cardiac disease

Exploring the transport of plant metabolites using positron emitting radiotracers

Short-lived positron-emitting radiotracer techniques provide time-dependent data that are critical for developing models of metabolite transport and resource distribution in plants and their microenvironments. Until recently these techniques were applied to measure radiotracer accumulation in coarse regions along transport pathways. The recent application of positron emission tomography (PET) techniques to plant research allows for detailed quantification of real-time metabolite dynamics on previously unexplored spatial scales. PET provides dynamic information with millimeter-scale resolution on labeled carbon, nitrogen, and water transport over a small plant-size field of view. Because details at the millimeter scale may not be required for all regions of interest, hybrid detection systems that combine high-resolution imaging with other radiotracer counting technologies offer the versatility needed to pursue wide-ranging plant physiological and ecological research. In this perspective we describe a recently developed hybrid detection system at Duke University that provides researchers with the flexibility required to carry out measurements of the dynamic responses of whole plants to environmental change using short-lived radiotracers. Following a brief historical development of radiotracer applications to plant research, the role of radiotracers is presented in the context of various applications at the leaf to the whole-plant level that integrates cellular and subcellular signals and∕or controls