Vinculin haploinsufficiency impairs integrin-mediated costamere remodeling on stiffer microenvironments.

Vinculin (VCL) is a key adapter protein located in force-bearing costamere complexes, which mechanically couples the sarcomere to the ECM. Heterozygous vinculin frameshift genetic variants can contribute to cardiomyopathy when external stress is applied, but the mechanosensitive pathways underpinning VCL haploinsufficiency remain elusive. Here, we show that in response to extracellular matrix stiffening, heterozygous loss of VCL disrupts force-mediated costamere protein recruitment, thereby impairing cardiomyocyte contractility and sarcomere organization.

Conductive Microfibers Improve Stem Cell-Derived Cardiac Spheroid Maturation.

Conventional two-dimensional (2D) cardiomyocyte differentiation protocols create cells with limited maturity, which impairs their predictive capacity and has driven interest in three-dimensional (3D) engineered cardiac tissue models of varying maturity and scalability. Cardiac spheroids are attractive high-throughput models that have demonstrated improved functional and transcriptional maturity over conventional 2D differentiations. However, these 3D models still tend to have limited contractile and electrical maturity compared to highly engineered cardiac tissues; hence, we incorporated a library of conductive polymer microfibers in cardiac spheroids to determine if fiber properties could accelerate maturation.

Fundamental Insights into Copper-Epoxy Interfaces for High-Frequency Chip-to-Chip Interconnects.

Future processes and materials are needed to enable multichip packages with chip-to-chip (C2C) data rates of 50 GB/s or higher. This presents a fundamental challenge because of the skin effect, which exacerbates signal transmission losses at high frequencies. Our results indicate that smooth copper interconnects with relatively thin cuprous oxides (CuO, Cu) and amine-functional silane adhesion promoters improve interfacial adhesion with epoxy dielectrics by nearly an order of magnitude.

The Role of Sibling Patterns in the Educational Attainment of Hungarian Twins.

Studies concerning twins with a sociological focus are scarce in Hungary as well as international research, although the number of twin births has increased dramatically worldwide. The raising and education of twins are tasks demanding special attention from both the family and institutions. In our study we examine these aspects, looking back from adulthood, using the narrow scope of the available data from research based on the 'Hungarostudy 2021' database ( total: 7000; twins: 106).

Single-cell multi-modal integrative analyses highlight functional dynamic gene regulatory networks directing human cardiac development.

Illuminating the precise stepwise genetic programs directing cardiac development provides insights into the mechanisms of congenital heart disease and strategies for cardiac regenerative therapies. Here, we integrate in vitro and in vivo human single-cell multi-omic studies with high-throughput functional genomic screening to reveal dynamic, cardiac-specific gene regulatory networks (GRNs) and transcriptional regulators during human cardiomyocyte development. Interrogating developmental trajectories reconstructed from single-cell data unexpectedly reveal divergent cardiomyocyte lineages with distinct gene programs based on developmental signaling pathways.