ABSTRACT
The overexpression of proto-oncogene Bcl3 is observed in various cancers. Bcl3 is extensively phosphorylated and associates with homodimers of NF-κB p50 and p52 to regulate transcription. Through cellular and biochemical assays, we observed that phospho-mimetic Glu substitution at Ser366 in addition to previously studied Ser33, 114 and 446 is necessary to switch Bcl3 from an IκB-like inhibitor to a transcriptional activator. To study interactive features of p52 and Bcl3, and phosphorylation- mediated changes in Bcl3 that regulate DNA-binding by p52, we performed HDX-MS of both Bcl3 and p52 within various complexes. Nature of interactions within Bcl3:(p52:p52) complex in presence and absence of DNA, differential flexibility of Bcl3, and allosteric changes in Bcl3 upon phospho-modifications revealed why a facile accommodation of DNA requires phosphorylation. The inhibitory nature of unphosphorylated Bcl3 on DNA binding by p52:p52 also relieved by a C-terminal deletion of Bcl3. Overall, this study revealed mechanistic bases of how Bcl3 phosphorylation regulates transcriptional potential of NF-κB and intricate cell physiology, a dysregulation of which can lead to cancers.
ABSTRACT
Background: Due to advances in digital technology, it is possible to obtain digital dental models through intraoral scanning. The stereolithographic data collected from the scanner can subsequently be printed into a three-dimensional dental model in resinic material. However, the accuracy between digital dental models and printed dental models needs to be evaluated since it might affect diagnosis and treatment planning in orthodontic treatment. This study aimed to evaluate the accuracy of digital models scanned by a Trios intraoral scanner and three-dimensional dental models printed using a Formlabs 2 3D printer in linear measurements and Bolton analysis. Methods: A total of 35 subjects were included in this study. All subjects were scanned using a Trios intraoral scanner to obtain digital study models. Stereolithographic data from previous scanning was printed using a Formlabs 2 3D printer to obtain printed study models. Mesiodistal, intercanine, intermolar, and Bolton analysis from all types of study models were measured. The intraclass correlation coefficient was used to assess intraobserver and interobserver reliability. All data were then statistically analyzed. Results: The reliability tests were high for both intraobserver and interobserver reliability, which demonstrates high reproducibility for all measurements on all model types. Most of the data compared between study models showed no statistically significant differences, though some data differed significantly. However, the differences are considered clinically insignificant. Conclusion: Digital dental models and three-dimensional printed dental models may be used interchangeably with plaster dental models for diagnostic and treatment planning purposes. Keywords: Accuracy, 3D printing, digital dental model, printed dental model.
