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Hui-Ju Yang Pin-Chun Chen Chien-Ting Huang Tzu-Lin Cheng Sheng-Ping Hsu Chien-Yu Chen Juu-Chin Lu Chih-Tien Wang 《The Journal of neuroscience》2021,41(13):2828
Common fusion machinery mediates the Ca2+-dependent exocytosis of synaptic vesicles (SVs) and dense-core vesicles (DCVs). Previously, Synapsin Ia (Syn Ia) was found to localize to SVs, essential for mobilizing SVs to the plasma membrane through phosphorylation. However, whether (or how) the phosphoprotein Syn Ia plays a role in regulating DCV exocytosis remains unknown. To answer these questions, we measured the dynamics of DCV exocytosis by using single-vesicle amperometry in PC12 cells (derived from the pheochromocytoma of rats of unknown sex) overexpressing wild-type or phosphodeficient Syn Ia. We found that overexpression of phosphodeficient Syn Ia decreased the DCV secretion rate, specifically via residues previously shown to undergo calmodulin-dependent kinase (CaMK)-mediated phosphorylation (S9, S566, and S603). Moreover, the fusion pore kinetics during DCV exocytosis were found to be differentially regulated by Syn Ia and two phosphodeficient Syn Ia mutants (Syn Ia-S62A and Syn Ia-S9,566,603A). Kinetic analysis suggested that Syn Ia may regulate the closure and dilation of DCV fusion pores via these sites, implying the potential interactions of Syn Ia with certain DCV proteins involved in the regulation of fusion pore dynamics. Furthermore, we predicted the interaction of Syn Ia with several DCV proteins, including Synaptophysin (Syp) and soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) proteins. By immunoprecipitation, we found that Syn Ia interacted with Syp via phosphorylation. Moreover, a proximity ligation assay (PLA) confirmed their phosphorylation-dependent, in situ interaction on DCVs. Together, these findings reveal a phosphorylation-mediated regulation of DCV exocytosis by Syn Ia.SIGNIFICANCE STATEMENT Although they exhibit distinct exocytosis dynamics upon stimulation, synaptic vesicles (SVs) and dense-core vesicles (DCVs) may undergo co-release in neurons and neuroendocrine cells through an undefined molecular mechanism. Synapsin Ia (Syn Ia) is known to recruit SVs to the plasma membrane via phosphorylation. Here, we examined whether Syn Ia also affects the dynamics of DCV exocytosis. We showed that Syn Ia regulates the DCV secretion rate and fusion pore kinetics during DCV exocytosis. Moreover, Syn Ia-mediated regulation of DCV exocytosis depends on phosphorylation. We further found that Syn Ia interacts with Synaptophysin (Syp) on DCVs in a phosphorylation-dependent manner. Thus, these results suggest that Syn Ia may regulate the release of DCVs via phosphorylation. 相似文献
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Meng-Ni Wu Pen-Tzu Fang Chih-Hsien Hung Chung-Yao Hsu Ping-Song Chou Yuan-Han Yang 《Medicine》2021,100(17)
Disrupted blood–brain barrier (BBB) in patients with ischemic stroke plays a critical role in malignant middle cerebral artery infarction (MMI) development.Cerebral white matter changes (WMC), particularly in the deep subcortical area or in severe one, may be also underlain by disrupted BBB. It is unclear whether the presence of WMC with potential premorbid disruption of BBB makes patients susceptible to MMI. Therefore, this study aimed to clarify any putative relationship between the MMI and WMC in terms of their severity and locations.In this case–control study, patients with infarction in the middle cerebral artery territory were retrospectively reviewed. Brain magnetic resonance images were analyzed according to Fazekas scale, and identified WMC were divided into periventricular WMC (PV-WMC) and deep subcortical WMC (deep-WMC). Patients were scored as having WMC, PV-WMC, deep-WMC, severe PV-WMC, and severe deep-WMC according to the severity and locations. Patients were defined as having MMI if either a progressive conscious disturbance or signs of uncal herniation was recorded in combination with a midline shift >5 mm identified on the follow-up computed tomography.Among 297 patients admitted between July 2009 and February 2015, 92 patients were eligible for final analysis. Compared to patients without MMI, patients with MMI had a higher score of National Institutes of Health Stroke Scale, a larger infarct volume, and an increasingly greater proportion of severe PV-WMC, deep-WMC, and severe deep-WMC, respectively. After adjustment for sex, age, infarct volume, and history of hypertension, severe deep-WMC (odds ratio [OR] = 6.362, 95% confidence interval [CI] = 1.444–28.023, P = .0144) and severe PV-WMC (odds ratio = 5.608, 95% confidence interval = 1.107–28.399, P = .0372) were significantly associated with MMI development.MMI and WMC are significantly associated such that MMI development is more likely when PV-WMC or deep-WMC is more severe. We hypothesize that Fazekas scale-defined severe deep-WMC and PV-WMC may be considered as clinically approachable predictors of MMI development. These findings support that the WMC with potential premorbid disrupted BBB may make patients susceptible to MMI, and further prospective study should be conducted to clarify this hypothesis. 相似文献
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Jia-Ming Chen Ping-Fang Chiu Feng-Mei Wu Po-Chi Hsu Li-Jyun Deng Chia-Chu Chang John Y. Chiang Lun-Chien Lo 《Medicine》2021,100(9)
Background:Traditional Chinese medicine (TCM) tongue diagnosis plays an important role in differentiation of symptoms because the tongue reflects the physiological and pathological condition of the body. The automatic tongue diagnosis system (ATDS), which noninvasively captures tongue images, can provide objective and reliable diagnostic information. Chronic kidney disease (CKD) currently is an important global public health problem and contributor to morbidity and mortality from non-communicable diseases. Thus, it is interesting to analyze and probe the relationship between tongue examination and CKD.Methods:This protocol is a cross-sectional, case-controlled observational study investigating the usefulness of the ATDS in clinical practice by examining its efficacy as a diagnostic tool for CKD. Volunteers over 20 years old with and without CKD will be enrolled. Tongue images will be captured and the patients divided into 2 groups: CKD group and healthy group. Nine primary tongue features will be extracted and analyzed, including tongue shape, tongue color, tooth mark, tongue fissure, fur color, fur thickness, saliva, ecchymosis, and red dots.Result:The results of this study will systematically evaluate tongue manifestations of patients and examine its efficacy as an early detection and diagnosis of CKD.Discussion:The aim of this protocol is to investigate discriminating tongue features to distinguish between CKD and normal people, and establish differentiating index to facilitate the noninvasive detection of CKD.Trial registries:ClinicalTrials.gov; Identifier: . NCT04708743相似文献
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T.-Y. Huang Y.-J. Hsia M.-Y. Sung Y.-T. Wu P.-C. Hsu 《International journal of oral and maxillofacial surgery》2021,50(8):1100-1106
Zygomatic implant treatment is widely applied for severe maxillary atrophy to help rehabilitate the maxillary dentition. This retrospective study was performed to evaluate the actual radiographic bone–implant contact (rBIC) lengths of zygomatic implants. The records of 28 patients who underwent zygomatic implant surgery and subsequent follow-up examinations between August 2013 and September 2018 in the Department of Oral and Maxillofacial Surgery, Taipei Tzu Chi Hospital were reviewed. The surgeries were performed by a single surgeon using the same treatment protocol. All patients had a computed tomography scan at 1 year after the surgery. Using three-dimensional imaging software, an investigator measured the rBIC lengths of 66 implants and documented their clinical status. The implant survival rate was 100%. The mean rBIC length was significantly longer in male patients than in female patients (20.80 ± 5.88 mm versus 17.79 ± 6.34 mm; P = 0.028). The mean rBIC length of double zygomatic implants was significantly longer when compared to that of single implants (21.11 ± 6.23 mm versus 17.75 ± 5.85 mm; P = 0.027). This article is novel in reporting the exact rBIC lengths of zygomatic implants in a clinical setting. The results showed that zygomatic implants are a viable treatment modality for full-mouth rehabilitation. 相似文献
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