The transforming growth factor beta (TGF-β) is a cytokine that is known for its immunoregulatory and also pro-fibrotic properties that are critically involved in airway remodeling during asthma . This dual property has been associated to the fact that TGF-β1 induces immunosuppressive T regulatory cells and together with IL-6 induces TH17-dominated immune response . TGF-β is secreted in an inactive, latent form bound to the latency-associated protein (LAP). The LAP-TGF-β complex can be linked to glycoprotein A repetitions predominant (GARP), which is a transmembrane protein known to bind LAP-TGF-β on different cell types [16,17]. GARP expression on immune cells promotes tolerance, preventing inflammation in diseases like allergies. The mature TGF-β1 homodimer is released upon degradation of LAP. Activators of this process can be integrins like αvβ6 or αvβ8 integrin .
Our previous publication on the PreDicta cohort showed similar results in preschool children . Rhinovirus infection reduced TGF-β production markedly, while in contrast to our adult participants, there was an induction of TGF-βRII mRNA levels in the RV-infected cells. The adult asthmatics showed higher TGF-βRII gene expression in untouched PBMC. It might be that asthmatic subjects, capture free TGF-β via binding to TGF-βRII without exerting any signal transduction, as TGF-βRI is not differentially regulated. On the other hand, this could represent a better responsiveness to TGF-β1 binding and could therefore drive tissue remodeling in the asthmatic patients with higher receptor expression . Moreover, TGF-β receptors are also known to undergo various posttranslational modifications that might alter the receptor activity . Further investigations in this direction would be needed.
Biomolecular dynamics of proteins and nucleic acids can be detected by smFRET and other single-molecule techniques. Extracting testable kinetic rate models from the experimental time traces is complicated by experimental shortcomings. Multiple labs joined forces to directly test the performance of diverse analytical approaches to infer kinetic rate constants in a blind study.
The power-driven devices were utilized to remove plaque from model teeth in dummy heads. The percentage of residual artificial plaque after 2 min of supra- or subgingival instrumentation was calculated by means of image-processing techniques at four sites (n = 576) of each tooth. The Health-Risk-Index (HRI: spatter/residual plaque quotient) with the different power-driven devices was assessed during treatment. 2b1af7f3a8