Emergence of glycogen synthase kinase-3 interaction domain enhances phosphorylation of SARS-CoV-2 nucleocapsid protein

A structural protein of SARS-CoV-2, nucleocapsid (N) protein is abundantly expressed during viral replication. The N protein is phosphorylated by glycogen synthase kinase (GSK)-3 on the serine/arginine (SR) rich motif located in disordered regions. Although phosphorylation by GSK-3{beta} constitutes a critical event for viral replication, the molecular mechanism underlying N phosphorylation is not well understood. In this study, we found the putative alpha-helix L/FxxxL/AxxRL motif known as the GSK-3 interacting domain (GID), commonly found in many endogenous GSK-3{beta} binding proteins, such as Axins, FRATs, WWOX and GSKIP. Indeed, N interacts with GSK-3{beta} similarly to Axin, and Leu to Glu substitution of the GID abolished the interaction, with loss of N phosphorylation. Unlike with endogenous GID proteins, the N interaction neither disturbs endogenous GSK-3 activity nor regulates subsequent canonical Wnt activity and the Snail-EMT program. Notably, N abundance in SARS-CoV-2 is incomparably high compared to other coronaviruses, such as 229E, OC43 and HKU1. Compared to other coronaviruses, N harbors a CDK1 primed phosphorylation site and Gly-rich linker for enhanced phosphorylation by GSK-3{beta}. Furthermore, we found that the S202R mutant found in Delta and R203K/G204R mutant found in the Omicron variant allows increased abundance and hyper-phosphorylation of N. Our observations suggest that the emergence of GID and mutations for increased phosphorylation in N may have contributed to the emergence of SARS-CoV-2 and evolution of variants, respectively. Further study, especially in a BSL3-equipped facility, is required to elucidate the functional importance of GID and N phosphorylation in SARS-CoV-2 and variants.

Subcutaneous emphysema related to dental procedures

OBJECTIVES: The objective of this study was to analyze 11 cases of subcutaneous emphysema associated with dental procedures from a single hospital and discuss approaches for accurate diagnosis and treatment of the condition. MATERIALS AND METHODS: The medical records of 11 patients who were treated for subcutaneous emphysema related to dental procedures between January 2009 and April 2017 were analyzed retrospectively. Patients with subcutaneous emphysema within the facial area or that spread to the neck and beyond, including the facial region, were assigned to two groups and compared in terms of age, sex, and durations of antibiotic use, hospitalization, and follow-up until improvement. The correlation between location of the origin tooth and range of emphysema spread was analyzed. RESULTS: The average durations of antibiotic use during conservative treatment and follow-up until improvement were 8.55 days (standard deviation [SD], 4.46 days) and 1.82 weeks (SD, 1.19 weeks), respectively. There was no intergroup difference in duration of antibiotic use (P=0.329) or follow-up (P=0.931). Subcutaneous emphysema was more common after dental procedures involving the maxilla or posterior region than after those involving the mandible or anterior region. There was no significant difference in air distribution according to location of the air orifice (maxilla, mandible, or both; P=0.106). CONCLUSION: Upon adequate conservative treatment accompanied by prophylactic antibiotic treatment considering the risk of infection, patients showed signs of improvement within a few days or weeks. There was no significant difference in treatment period between patients with subcutaneous emphysema localized to the facial region and those with subcutaneous emphysema spreading to the neck or beyond. These findings need to be confirmed by analysis of additional cases.

Three-dimensional analysis of the anterior loop of the inferior alveolar nerve in relation to the growth pattern of the mandibular functional subunit / 대한악안면성형재건외과학회지

BACKGROUND: The purpose of the present study was to investigate the differences in the position and shape of the anterior loop of the inferior alveolar nerve (ALIAN) in relation to the growth pattern of the mandibular functional subunit. METHODS: The study was conducted on 56 patients among those who had undergone orthognathic surgery at the Gangnam Severance Hospital between January 2010 and December 2015. Preoperative computerized tomography (CT) images were analyzed using the Simplant OMS software (ver.14.0 Materialise Medical, Leuven, Belgium). The anterior and inferior lengths of ALIAN (dAnt and dInf) and each length of the mandibular functional subunits were measured. The relationship between dAnt, dInf, and the growth pattern of the mandibular subunits was analyzed. RESULTS: The length of the anterior portion of ALIAN (dAnt) reached 3.34 ± 1.59 mm in prognathism and 1.00 ± 0.97 mm in retrognathism. The length of the inferior portion of ALIAN (dInf) reached 6.81 ± 1.33 mm in prognathism and 5.56 ± 1.34 mm in retrognathism. The analysis of Pearson’s correlation coefficiency on all samples showed that the lengths of functional subunits were positively correlated with the loop depth. The length of the symphysis area in prognathic patients was positively correlated with the anterior loop depth (p = 0.005). CONCLUSIONS: Both the anterior and inferior length of ALIAN are longer in prognathic patients. Especially, it seems to be associated with the growth of the symphysis area.