Changes in subcellular structures and states of pumilio 1 regulate the translation of target Mad2 and cyclin B1 mRNAs.

Temporal and spatial control of mRNA translation has emerged as a major mechanism for promoting diverse biological processes. However, the molecular nature of temporal and spatial control of translation remains unclear. In oocytes, many mRNAs are deposited as a translationally repressed form and are translated at appropriate times to promote the progression of meiosis and development. Here, we show that changes in subcellular structures and states of the RNA-binding protein pumilio 1 (Pum1) regulate the translation of target mRNAs and progression of oocyte maturation. Pum1 was shown to bind to Mad2 (also known as Mad2l1) and cyclin B1 mRNAs, assemble highly clustered aggregates, and surround Mad2 and cyclin B1 RNA granules in mouse oocytes. These Pum1 aggregates were dissolved prior to the translational activation of target mRNAs, possibly through phosphorylation. Stabilization of Pum1 aggregates prevented the translational activation of target mRNAs and progression of oocyte maturation. Together, our results provide an aggregation-dissolution model for the temporal and spatial control of translation.

Pumilio1 phosphorylation precedes translational activation of its target mRNA in zebrafish oocytes.

SummaryTranslational regulation of mRNAs is crucial for promoting various cellular and developmental processes. Pumilio1 (Pum1) has been shown to play key roles in translational regulation of target mRNAs in many systems of diverse organisms. In zebrafish immature oocytes, Pum1 was shown to bind to cyclin B1 mRNA and promote the formation of cyclin B1 RNA granules. This Pum1-mediated RNA granule formation seemed critical to determine the timing of translational activation of cyclin B1 mRNA during oocyte maturation, leading to activation of maturation/M-phase-promoting factor (MPF) at the appropriate timing. Despite its fundamental importance, the mechanisms of translational regulation by Pum1 remain elusive. In this study, we examined the phosphorylation of Pum1 as a first step to understand the mechanisms of Pum1-mediated translation. SDS-PAGE analyses and phosphatase treatments showed that Pum1 was phosphorylated at multiple sites during oocyte maturation. This phosphorylation began in an early period after induction of oocyte maturation, which preceded the polyadenylation of cyclin B1 mRNA. Interestingly, depolymerization of actin filaments in immature oocytes caused phosphorylation of Pum1, disassembly of cyclin B1 RNA granules, and polyadenylation of cyclin B1 mRNA but not translational activation of the mRNA. Overexpression of the Pum1 N-terminus prevented the phosphorylation of Pum1, disassembly of cyclin B1 RNA granules, and translational activation of the mRNA even after induction of oocyte maturation. These results suggest that Pum1 phosphorylation in the early period of oocyte maturation is one of the key processes for promoting the disassembly of cyclin B1 RNA granules and translational activation of target mRNA.

Verification of a Three-day Hospitalization Protocol for Chronic Subdural Hematoma Surgery.

Chronic subdural hematoma (CSH) is predominantly a disease of the elderly. Aging societies in advanced countries are seeing the number of CSH cases increasing. We applied a three-day hospitalization protocol for CSH surgery to reduce healthcare costs and more efficiently manage hospital beds. We investigated the clinical factors that influenced prolonged hospitalization. From January 2015 to December 2020, we performed irrigation, evacuation, and drainage of CSH cases in 221 consecutive patients. The χ2 test and logistic regression analysis were conducted to detect clinical factors influencing prolonged hospitalization. A p-value below 0.05 was considered statistically significant. Applying a three-day hospitalization protocol showed no adverse outcomes. Fifty-two (24%) of 221 patients experienced prolonged hospitalization. The χ2 test showed that female gender, atrial fibrillation, alcohol abuse, preoperative consciousness level, verbal function disturbance, and perioperative activities of daily living were significantly related to prolonged hospitalization. Female gender, atrial fibrillation, and alcohol abuse were significant factors in the logistic regression analysis. A three-day hospitalization protocol for CSH is suitable for patient care; however, particular attention needs to be focused on the female gender, atrial fibrillation, and alcohol abuse, all three of which prolong hospitalization.

Acute myocardial infarction caused by delayed heparin-induced thrombocytopenia and acute immunoreaction due to re-exposure to heparin in a systemic lupus erythematosus patient with HIT antibodies.

A patient with systemic lupus erythematosus and anticardiolipin antibodies and antibodies to platelet factor 4/heparin complexes suffered an acute myocardial infarction caused by delayed heparin-induced thrombocytopenia after heparin administration given to treat pulmonary hypertension. Furthermore, additional heparin administration for emergency coronary angiography appeared to have led to an acute immunoreaction, which might have resulted in acute coronary occlusion during coronary angiography and to a decreased platelet count. The present findings suggest that one must suspect delayed-type HIT in rare cases of induction of thrombosis after the cessation of heparin treatment, and avoid re-exposure to heparin in such cases.