Splanchnic mesoderm in the region described as the second heart field (SHF)is marked by Islet1 expression in the mouse embryo. The anterior part of this region expresses a number of markers, including Fgf10, and the contribution of these cells to outflow tract and right ventricular myocardium has been established. We now show that the posterior region also has myocardial potential, giving rise specifically to differentiated cells of the atria. This conclusion is based on explant experiments using endogenous and transgenic markers and on DiI labelling, followed by embryo culture. Progenitor cells in the right or left posterior SHF contribute to the right or left common atrium, respectively. Explant experiments with transgenic embryos,in which the transgene marks the right atrium, show that atrial progenitor cells acquire right-left identity between the 4- and 6-somite stages, at the time when Pitx2c is first expressed. Manipulation of Pitx2c, by gain-and loss-of-function, shows that it represses the transgenic marker of right atrial identity. A repressive effect is also seen on the proliferation of cells in the left sinus venosus and in cultured explants from the left side of the posterior SHF. This report provides new insights into the contribution of the SHF to atrial myocardium and the effect of Pitx2c on the formation of the left atrium.

Reactive oxygen species (ROS) and mitochondria play a pivotal role in regulating platelet functions. Platelet activation determines a drastic change in redox balance and in platelet metabolism. Indeed, several signaling pathways have been demonstrated to induce ROS production by NAPDH oxidase (NOX) and mitochondria, upon platelet activation. Platelet-derived ROS, in turn, boost further ROS production and consequent platelet activation, adhesion and recruitment in an auto-amplifying loop. This vicious circle results in a platelet procoagulant phenotype and apoptosis, both accounting for the high thrombotic risk in oxidative stress-related diseases. This review sought to elucidate molecular mechanisms underlying ROS production upon platelet activation and the effects of an altered redox balance on platelet function, focusing on the main advances that have been made in platelet redox biology. Furthermore, given the increasing interest in this field, we also describe the up-to-date methods for detecting platelets, ROS and the platelet bioenergetic profile, which have been proposed as potential disease biomarkers.

The genes coding for white collar‐1 and white collar‐2 (wc‐1 and wc‐2 ) have been isolated previously, and their products characterized as Zn‐finger transcription factors involved in the control of blue light‐induced genes. Here, we show that the PAS dimerization domains present in both proteins enable the WC‐1 and WC‐2 proteins to dimerize in vitro. Homodimers and heterodimers are formed between the white collar (WC) proteins. A computer analysis of WC‐1 reveals a second domain, called LOV, also identified in NPH1, a putative blue light photoreceptor in plants and conserved in redox‐sensitive proteins and in the phytochromes. The WC‐1 LOV domain does not dimerize with canonical PAS domains, but it is able to self‐dimerize. The isolation of three blind wc‐1 strains, each with a single amino acid substitution only in the LOV domain, reveals that this region is essential for blue light responses in Neurospora. The demonstration that the WC‐1 proteins in these LOV mutants are still able to self‐dimerize suggests that this domain plays an additional role, essential in blue light signal transduction.

Bioactive glasses synthesized by the sol-gel technique possess many of the qualities associated with an ideal scaffold material for a bone graft substitute. In view of the potential clinical applications, we performed a detailed in vitro study of the biological reactivity of synthesized 58S bioactive glass containing-zinc, in terms of osteoblast morphology, proliferation, and deposition of a mineralized extracellular matrix (ECM). Human Sarcoma Osteoblast (SAOS-2) cells were used to i) assess cytotoxicity by lactate dehydrogenase (LDH) release and ii) evaluate the deposition of a calcified extracellular matrix by ELISA assay and quantitative RT-PCR (qRT-PCR). In comparison with pure silica and 58S, the 58S-Zn0.4 bioglass showed a significant increase in cellular proliferation and deposition of ECM components such as decorin, fibronectin, osteocalcin, osteonectin, osteopontin, type-I and -III collagens. Calcium deposition was significantly higher than on pure silica and 58S samples. Also Alkaline phosphatase (ALP) activity and its protein content was higher with respect to pure silica and 58S. qRT-PCR analysis revealed the up-regulation of type-I collagen, bone sialoprotein and osteopontin genes. All together these results demonstrate the cytocompatibility of 58S-Zn0.4 bioglass and its capability to promote osteoblast differentiation.

Objective— To test the potential of mesoangioblasts (Mabs) in reducing postischemic injury in comparison with bone marrow progenitor cells (BMPCs), fibroblasts (Fbs), and embryonic stem cell–derived endothelial cells (ECs), and to identify putative cellular protective mechanisms. Methods and Results— Cells were injected percutaneously in the left ventricular (LV) chamber of C57BL/6 mice, 3 to 6 hours after coronary ligation, and detected in the hearts 2 days and 6 weeks later. Echocardiographic examinations were performed at 6 weeks. LV dilation was reduced and LV shortening fraction was improved with Mabs and BMPCs but not with ECs and Fbs. Donor cell colonization of the host myocardium was modest and predominantly in the smooth muscle layer of vessels. Capillary density was higher in the peripheral infarct area and apoptotic cardiomyocytes were fewer with Mabs and BMPCs. Mabs and BMPCs, but not Fbs or ECs, promoted survival of cultured cardiocytes under low-oxygen in culture. This activity was present in Mab-conditioned medium and could be replaced by a combination of basic fibroblast growth factor (bFGF), insulin-like growth factor (IGF)-1, and hepatocyte growth factor (HGF), all of which are produced by these cells. Conditioned medium from Mabs, but not from Fbs, stimulated proliferation of smooth muscle cells in vitro. Conclusions— Mabs appear as effective as BMPCs in reducing postinfarction LV dysfunction, likely through production of antiapoptotic and angiogenic factors.