To examine the mechanism of the network formation of silk fibroin (SF), monodispersed colloidal particles (MDCPs) are used as well defined foreign substrates to quantify their effect on the primary nucleation of β‐crystallites in molecular networks (silk nanofibrils) and the hierarchical network formation of SF. It follows that MDCPs are capable of accelerating the SF gelation by reducing the multistep nucleation barrier, which gives rise to a high density of silk fibril domain networks due to the increase of primary nucleation sites. Consequently, through governing the change in the hierarchical mesoscopic structure, the macroscopic performance of silk materials (e.g., the rheological properties of SF hydrogels and the tensile stress of fibers) can be controlled directly. As SF hydrogels represent a typical example of weak fibril domain–domain network interactions, the increase of fibril domain density leads to weaker gels. On the other hand, SF fibers correspond to strong fibril domain–domain network interactions, the increase of fibril domain density ends up with much tougher fibers. The knowledge obtained provides a facile strategy in controlling the complex hierarchical structure and macroscopic performance of SF materials, and offers useful routes for general design and functionalization of soft materials.

Background:The NFAT signaling pathway is linked to pulmonary arterial hypertension. Results: MicroRNA screening revealed that miR-124 robustly inhibits NFAT activity, dephosphorylation, and nuclear translocation of NFAT by targeting multiple genes, NFATc1, CAMTA1, and PTBP1. Conclusion: miR-124 is an effective and multipronged inhibitor of NFAT signaling. Significance: miR-124 might be a potential immunosuppressant that may have biological effects linked to pulmonary arterial hypertension.

Gene regulatory divergence is thought to play a central role in determining human-specific traits. However, our ability to link divergent regulation to divergent phenotypes is limited. Here, we utilized human-chimpanzee hybrid induced pluripotent stem cells to study gene expression separating these species. The tetraploid hybrid cells allowed us to separate cis - from trans -regulatory effects, and to control for non-genetic confounding factors. We differentiated these cells into cranial neural crest cells (CNCCs), the primary cell type giving rise to the face. We discovered evidence of lineage-specific selection on the hedgehog signaling pathway, including a human-specific 6-fold down-regulation of EVC2 (LIMBIN) , a key hedgehog gene. Inducing a similar down-regulation of EVC2 substantially reduced hedgehog signaling output. Mice and humans lacking functional EVC2 show striking phenotypic parallels to human-chimpanzee craniofacial differences, suggesting that the regulatory divergence of hedgehog signaling may have contributed to the unique craniofacial morphology of humans.

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