Compound exocytosis is considered the most massive mode of exocytosis, during which the membranes of secretory granules (SGs) fuse with each other to form a channel through which the entire contents of their granules is released. The underlying mechanisms of compound exocytosis remain largely unresolved. Here we show that the small GTPase Rab5, a known regulator of endocytosis, is pivotal for compound exocytosis in mast cells. Silencing of Rab5 shifts receptor-triggered secretion from a compound to a full exocytosis mode, in which SGs individually fuse with the plasma membrane. Moreover, we show that Rab5 is essential for FcεRI-triggered association of the SNARE protein SNAP23 with the SGs. Direct evidence is provided for SNAP23 involvement in homotypic SG fusion that occurs in the activated cells. Finally, we show that this fusion event is prevented by inhibition of the IKKβ2 kinase, however, neither a phosphorylation-deficient nor a phosphomimetic mutant of SNAP23 can mediate homotypic SG fusion in triggered cells. Taken together our findings identify Rab5 as a heretofore-unrecognized regulator of compound exocytosis that is essential for SNAP23-mediated granule-granule fusion. Our results also implicate phosphorylation cycles in controlling SNAP23 SNARE function in homotypic SG fusion.
BackgroundIliosacral screw fixation has become a common method for surgical stabilization of acute disruptions of the pelvic ring. Placement of iliosacral screws into the first sacral (S1) body is the preferred method of fixation, but size limitations and sacral dysmorphism may preclude S1 fixation. In these clinical situations, fixation into the second sacral (S2) body has been recommended. The objective of this study was to evaluate the bone quality of the S1 compared to S2 in the described “safe zone” of iliosacral screw fixation in trauma patients.Materials and methodsThe pelvic computed tomography scans of 25 consecutive trauma patients, ages 18–49, at a level 1 trauma center were prospectively analyzed. Hounsfield units, a standardized computed tomography attenuation coefficient, was utilized to measure regional cancellous bone mineral density of the S1 and S2. No change in the clinical protocol or treatment occurred as a consequence of inclusion in this study.ResultsA statically significant difference in bone quality was found when comparing the first and second sacral segment (p = 0.0001). Age, gender, or smoking status did not independently affect bone quality.ConclusionIn relatively young, otherwise healthy trauma patients there is a statistically significant difference in the bone density of the first sacral segment compared to the second sacral segment. This study highlights the need for future biomechanical studies to investigate whether this difference is clinically relevant. Due to the relative osteopenia in the second sacral segment, which may impact the quality of fixation, we feel this technique should be used with caution.Level of evidenceIII
Хлопчик О., народжений на 38-му тижні гестації від V вагітності, III пологів (у матері було два викид-ні). Маса при народженні 2300 г. Стан після наро-дження задовільний.Дитина надійшла у відділення патології ново-народжених комунальної міської дитячої клінічної лікарні м. Львова на 26-й день життя.Анамнез захворювання: зі слів матері, хлопчик хворіє 5-ту добу. Захворювання почалося з нежиті, на 2-гу добу приєдналися кашель і задишка.Âèïàäîê ³ç ïðàêòèêè / Case Report ® Стан при надходженні тяжкий. Огляд. Наявний періоральний ціаноз. Тургор тканин задовільний. Дихання носом утруднене че-рез масивний набряк носових ходів. При аускульта-ції в легенях жорстке дихання, з обох сторін вологі хрипи, що дуже повільно зменшувалися впродовж лікування, та спостерігався короткочасний ефект після інгаляційно-дренажної терапії. Звертала на себе увагу нетипова картина бронхообструктивного синдрому, що мав затяжний перебіг і повністю не регресував на фоні призначеного лікування.УДК 616.132.14-053.2-036-07 DOI: 10.22141/2224616.132.14-053.2-036-07 DOI: 10.22141/ -0551.12.5.2017 Áåø Ë.Â.
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