Do binucleate cardiomyocytes have a role in myocardial repair? Insights using isolated rodent myocytes and cell culture.

Neonatal and adult cardiomyocytes were isolated from rat hearts. Some of the adult myocytes were cultured to allow for cell dedifferentiation, a phenomenon thought to mimic cell changes that occur in stressed myocardium, with myocytes regressing to a fetal pattern of metabolism and stellate neonatal shape.Using fluorescence deconvolution microscopy, cells were probed with fluorescent markers and scanned for a number of proteins associated with ion control, calcium movements and cardiac function. Image analysis of deconvoluted image stacks and sequential real-time image recordings of calcium transients of cells were made.All three myocyte groups were predominantly comprised of binucleate cells. Clustering of proteins to a single nucleus was a common observation, suggesting that one nucleus is active in protein synthesis pathways, while the other nucleus assumes a 'dormant' or different role and that cardiomyocytes might be mitotically active even in late development, or specific protein syntheses could be targeted and regulated for reintroduction into the cell cycle.Such possibilities would extend cardiac disease associated stem cell research and therapy options, while producing valuable insights into developmental and death pathways of binucleate cardiomyocytes (word count 183).

A blood-borne PDGF/VEGF-like ligand initiates wound-induced epidermal cell migration in Drosophila larvae

Wound healing is a conserved survival response whose function is to restore the integrity of the tissue after physical trauma. Despite numerous studies in the wound healing field, the signals and pathways that orchestrate and control the wound healing program are still not entirely known. To identify additional signals and pathways that regulate epidermal wound repair in Drosophila larvae, we performed a pilot in vivo RNAi screen using a live reporter for epidermal morphology and a wounding assay. From our pilot screen we identified Pvr, the Drosophila homolog of the vertebrate PDGF/VEGF receptors, and six other genes as epidermal wound healing genes. Morphological analysis of wound-edge cells lacking Pvr or the Drosophila Jun N-terminal Kinase (JNK), previously implicated in larval wound closure, suggest that Pvr signaling leads to cell process extension into the wound site while JNK mediates transient dedifferentiation of wound-edge epidermal cells. Furthermore, we found that one of the three known Pvr ligands, Pvf1, is also required for epidermal wound closure. Through tissue-specific knock down and rescue experiments, we propose a model in which epidermally-produced Pvf1 may be sequestered into the hemolymph (blood) and that tissue damage locally exposes blood-borne Pvf1 to Pvr receptors on epidermal cells at the wound edge, thus initiating epidermal cell process extension and migration into the wound gap. Together, our data suggest that the Pvr and JNK signaling pathways act in parallel to control different aspects of wound closure and that PDGF/VEGF ligands and receptors may have a conserved autocrine role in epidermal wound closure. ^