Is Etiology a Key Factor for Regenerative Endodontic Treatment Outcomes?

INTRODUCTION: This study aimed to evaluate treatment outcomes of regenerative endodontic treatment (RET) in nonvital immature permanent teeth due to developmental malformation and trauma, and to analyze the influence of etiology on the prognosis. METHODS: Fifty-five cases were included and divided into a malformation group (n = 33) and a trauma group (n = 22). Treatment outcomes were classified as healed, healing, and failure. Root development was evaluated in terms of root morphology and the percentage changes in root length, root width, and apical diameter during a follow-up period of 12-85 months (mean 30.8 months). RESULTS: The mean age and the mean degree of root development in the trauma group were significantly younger than that in the malformation group. The success rate of RET was 93.9% (81.8% healed, 12.1% healing) in the malformation group and 90.9% (68.2% healed, 22.7% healing) in the trauma group, showing no statistically significant difference. The proportion of type I-III root morphology in the malformation group (97%, 32/33) was significantly higher than that in the trauma group (77.3%, 17/22) (P < .05), whereas there was no significant difference in the percentage changes of root length, root width, and apical diameter between the 2 groups. Six cases (6/55, 10.9%) showed no significant root development (type IV-V) (1 in the malformation group and 5 in the trauma group). Six cases (6/55, 10.9%) revealed intracanal calcification. CONCLUSIONS: RET achieved reliable outcomes regarding the healing of apical periodontitis and continued root development. The etiology seems to influence the outcome of RET. Malformation cases presented with a better prognosis than trauma cases after RET.

Site-specific phosphorylation of PSD-95 dynamically regulates the postsynaptic density as observed by phase separation.

Postsynaptic density protein 95 is a key scaffolding protein in the postsynaptic density of excitatory glutamatergic neurons, organizing signaling complexes primarily via its three PSD-95/Discs-large/Zona occludens domains. PSD-95 is regulated by phosphorylation, but technical challenges have limited studies of the molecular details. Here, we genetically introduced site-specific phosphorylations in single, tandem, and full-length PSD-95 and generated a total of 11 phosphorylated protein variants. We examined how these phosphorylations affected binding to known interaction partners and the impact on phase separation of PSD-95 complexes and identified two new phosphorylation sites with opposing effects. Phosphorylation of Ser78 inhibited phase separation with the glutamate receptor subunit GluN2B and the auxiliary protein stargazin, whereas phosphorylation of Ser116 induced phase separation with stargazin only. Thus, by genetically introducing phosphoserine site-specifically and exploring the impact on phase separation, we have provided new insights into the regulation of PSD-95 by phosphorylation and the dynamics of the PSD.

Catalytic Asymmetric [3 + 2] Annulation of Hantzsch Esters with Racemic N-Sulfonylaziridines.

Hantzsch esters (HEs) served as two-carbon partners in a copper(I)-catalyzed enantioselective [3 + 2] annulation with racemic 2-(hetero)aryl-N-sulfonyl aziridines via kinetic resolution to provide pyrrolo[2,3-b]tetrahydropyridines containing multiple contiguous stereogenic centers including all-carbon quaternary centers in excellent yields and enantiopurities and moderate-to-excellent diastereoselectivities. Mainly dependent upon the structures of the aziridines, a competitive hydrogenolysis process with HEs as the hydrogen source was also observed in some cases.

Mechanisms underlying the synaptic trafficking of the glutamate delta receptor GluD1.

Ionotropic glutamate delta receptors do not bind glutamate and do not generate ionic current, resulting in difficulty in studying the function and trafficking of these receptors. Here, we utilize chimeric constructs, in which the ligand-binding domain of GluD1 is replaced by that of GluK1, to examine its synaptic trafficking and plasticity. GluD1 trafficked to the synapse, but was incapable of expressing long-term potentiation (LTP). The C-terminal domain (CT) of GluD1 has a classic PDZ-binding motif, which is critical for the synaptic trafficking of other glutamate receptors, but we found that its binding to PSD-95 was very weak, and deleting the PDZ-binding motif failed to alter synaptic trafficking. However, deletion of the entire CT abolished synaptic trafficking, but not surface expression. We found that mutation of threonine (T) T923 to an alanine disrupted synaptic trafficking. Therefore, GluD1 receptors have strikingly different trafficking mechanisms compared with AMPARs. These results highlight the diversity of ionotropic glutamate receptor trafficking rules at a single type of synapse. Since this receptor is genetically associated with schizophrenia, our findings may provide an important clue to understand schizophrenia.

Structural insights into ankyrin repeat-mediated recognition of the kinesin motor protein KIF21A by KANK1, a scaffold protein in focal adhesion.

Kidney ankyrin repeat-containing proteins (KANK1/2/3/4) belong to a family of scaffold proteins, playing critical roles in cytoskeleton organization, cell polarity, and migration. Mutations in KANK proteins are implicated in cancers and genetic diseases, such as nephrotic syndrome. KANK proteins can bind various target proteins through different protein regions, including a highly conserved ankyrin repeat domain (ANKRD). However, the molecular basis for target recognition by the ANKRD remains elusive. In this study, we solved a high-resolution crystal structure of the ANKRD of KANK1 in complex with a short sequence of the motor protein kinesin family member 21A (KIF21A), revealing that the highly specific target-binding mode of the ANKRD involves combinatorial use of two interfaces. Mutations in either interface disrupted the KANK1-KIF21A interaction. Cellular immunofluorescence localization analysis indicated that binding-deficient mutations block recruitment of KIF21A to focal adhesions by KANK1. In conclusion, our structural study provides mechanistic explanations for the ANKRD-mediated recognition of KIF21A and for many disease-related mutations identified in human KANK proteins.