Replication-independent incorporation of variant histone H3.3 has a profound impact on chromatin function and numerous cellular processes, including the differentiation of muscle cells. The histone chaperone HIRA and H3.3 have essential roles in MyoD regulation during myoblast differentiation. However, the precise mechanism that determines the onset of H3.3 deposition in response to differentiation signals is unclear. Here we show that HIRA is phosphorylated by Akt kinase, an important signaling modulator in muscle cells. By generating a phosphospecific antibody, we found that a significant amount of HIRA was phosphorylated in myoblasts. The phosphorylation level of HIRA and the occupancy of phosphorylated protein on muscle genes gradually decreased during cellular differentiation. Remarkably, the forced expression of the phosphomimic form of HIRA resulted in reduced H3.3 deposition and suppressed the activation of muscle genes in myotubes. Our data show that HIRA phosphorylation limits the expression of myogenic genes, while the dephosphorylation of HIRA is required for proficient H3.3 deposition and gene activation, demonstrating that the phosphorylation switch is exploited to modulate HIRA/H3.3-mediated muscle gene regulation during myogenesis.
Antibodies, Phospho-Specific ; Chromatin ; Histones* ; Muscle Cells* ; Muscle Development ; Muscle Fibers, Skeletal ; Myoblasts ; Phosphorylation* ; Phosphotransferases ; Transcriptional Activation

Objective: This study evaluated the accuracy of the pre-hospital shock index multiplied by the AVPU scale (PSIAVPU) as a predictor of massive transfusion (MT) and traumatic coagulopathy. Methods: This research was a retrospective single-center study that included patients consecutively presenting to a trauma center between 2017 and 2020. The predictive value of the PSIAVPU for MT, in-hospital mortality, and traumatic coagulopathy was measured using the area under the curve (AUC) of the receiver operating characteristic curve. The AUC of the PSIAVPU was compared with the Reverse Shock Index multiplied by the Glasgow Coma Scale (rSIG) measured at the trauma center presentation. Results: One thousand seven hundred and ninety-two patients were included, of which 163 patients (9.09%) received MT and 195 patients (10.88%) died during their hospital stay. Traumatic coagulopathy was observed in 245 patients. The AUC values for the PSIAVPU in terms of predicting MT, hospital mortality, and traumatic coagulopathy were 0.755, 0.752, and 0.736, respectively. Conclusion In patients with trauma, the predictive power of the PSIAVPU was higher than that of the prehospital shock index and was comparable to that of the rSIG. The PSIAVPU is a useful indicator that can be used easily and quickly for trauma patients at the prehospital stage.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel.There may be more transmissions with this VOC in Korea than reported.