Patients with Fibrodysplasia Ossificans Progressiva (FOP) suffer from ectopic bone formation, which progresses during life and results in dramatic movement restrictions. Cause of the disease are point mutations in the Activin A receptor type 1 (ACVR1), with p.R206H being most common. In this study we compared the signalling responses of ACVR1 and ACVR1 to different ligands. ACVR1, but not ACVR1 inhibited BMP signalling of BMP2 or BMP4 in a ligand binding domain independent manner. Likewise, the basal BMP signalling activity of the receptor BMPR1A or BMPR1B was inhibited by ACVR1, but enhanced by ACVR1. In comparison, BMP6 or BMP7 activated ACVR1 and caused a hyper-activation of ACVR1. These effects were dependent on an intact ligand binding domain. Finally, the neofunction of Activin A in FOP was tested and found to depend on the ligand binding domain for activating ACVR1. We conclude that the FOP mutation ACVR1 is more sensitive to a number of natural ligands. The mutant receptor apparently lost some essential inhibitory interactions with its ligands and co-receptors, thereby conferring an enhanced ligand-dependent signalling and stimulating ectopic bone formation as observed in the patients.

Oral paracoccidioidomycosis is an uncommon lesion observed in oral biopsy samples. The differences in the relative frequency of oral paracoccidioidomycosis are related to geographical variations. Men between 50 and 59 years are more affected. This study provides helpful information for clinicians in the diagnosis of oral paracoccidioidomycosis.

Collectively, these data suggest that ALDH1 immunostaining in the invasive front and in adjacent non-tumor epithelium may help identify tumors with a more aggressive behavior, potentially contributing to improving treatment customization and the monitoring of patients with head and neck cancer.

A significantly delayed DES coverage after CTO-PCI was observed. Given the known increased rate of ST following CTO-PCI and the known association between delayed DES coverage and ST, OCT may aid in determining the optimal duration of dual antiplatelet therapy after CTO-PCI.