Hippo Signaling Mediates TGFß-Dependent Transcriptional Inputs in Cardiac Cushion Mesenchymal Cells to Regulate Extracellular Matrix Remodeling.

The transforming growth factor beta (TGFß) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFß signaling and Hippo signaling are also important for cardiac cushion remodeling and septation during embryonic development. Loss of TGFß2 in mice causes cardiac cushion remodeling defects resulting in congenital heart disease. In this study, we used in vitro molecular and pharmacologic approaches in the cushion mesenchymal cell line (tsA58-AVM) and investigated if the Hippo pathway acts as a mediator of TGFß2 signaling. Immunofluorescence staining showed that TGFß2 induced nuclear translocation of activated SMAD3 in the cushion mesenchymal cells. In addition, the results indicate increased nuclear localization of Yes-associated protein 1 (YAP1) following a similar treatment of TGFß2. In collagen lattice formation assays, the TGFß2 treatment of cushion cells resulted in an enhanced collagen contraction compared to the untreated cushion cells. Interestingly, verteporfin, a YAP1 inhibitor, significantly blocked the ability of cushion cells to contract collagen gel in the absence or presence of exogenously added TGFß2. To confirm the molecular mechanisms of the verteporfin-induced inhibition of TGFß2-dependent extracellular matrix (ECM) reorganization, we performed a gene expression analysis of key mesenchymal genes involved in ECM remodeling in heart development and disease. Our results confirm that verteporfin significantly decreased the expression of α-smooth muscle actin (Acta2), collagen 1a1 (Col1a1), Ccn1 (i.e., Cyr61), and Ccn2 (i.e., Ctgf). Western blot analysis indicated that verteporfin treatment significantly blocked the TGFß2-induced activation of SMAD2/3 in cushion mesenchymal cells. Collectively, these results indicate that TGFß2 regulation of cushion mesenchymal cell behavior and ECM remodeling is mediated by YAP1. Thus, the TGFß2 and Hippo pathway integration represents an important step in understanding the etiology of congenital heart disease.

Influence of Ag Nanostructure Location on the Absorption Enhancement in Polymer Solar Cells.

The optical absorption enhancement in Ag nanocube (NC)- and nanosphere (NS)-embedded poly[ N-9'-heptadecanyl-2,7-carbazole- alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)]:[6,6]-phenyl C71-butyric acid methyl ester active layer was calculated using three-dimensional finite-difference time domain simulations. The simulations were carried out by incorporating Ag nanostructures as a two-dimensional array at various locations in the active layer matrix. High absorption enhancements of 53 and 61% were achieved with NSs and NCs, respectively, when they were incorporated at the top portion of the active layer. The influence of various passivation layers on the absorption enhancement was also investigated. The simulation results revealed that the absorption enhancement is mainly due to the near-field enhancement around the nanostructures and the backward reflection of incident light from the nanostructure array.