231 research outputs found

    Delayed Response to Radiofrequency Ablation of Accessory Connections

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72240/1/j.1540-8159.1993.tb01019.x.pd

    The brain-specific double-stranded RNA-binding protein Staufen2 is required for dendritic spine morphogenesis

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    Mammalian Staufen2 (Stau2) is a member of the double-stranded RNA-binding protein family. Its expression is largely restricted to the brain. It is thought to play a role in the delivery of RNA to dendrites of polarized neurons. To investigate the function of Stau2 in mature neurons, we interfered with Stau2 expression by RNA interference (RNAi). Mature neurons lacking Stau2 displayed a significant reduction in the number of dendritic spines and an increase in filopodia-like structures. The number of PSD95-positive synapses and miniature excitatory postsynaptic currents were markedly reduced in Stau2 down-regulated neurons. Akin effects were caused by overexpression of dominant-negative Stau2. The observed phenotype could be rescued by overexpression of two RNAi cleavage-resistant Stau2 isoforms. In situ hybridization revealed reduced expression levels of Ī²-actin mRNA and fewer dendritic Ī²-actin mRNPs in Stau2 down-regulated neurons. Thus, our data suggest an important role for Stau2 in the formation and maintenance of dendritic spines of hippocampal neurons

    Physical and functional interaction between the dopamine transporter and the synaptic vesicle protein synaptogyrin-3.

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    Uptake through the dopamine transporter (DAT) represents the primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that dopamine (DA) taken up by the transporter is used to replenish synaptic vesicle stores for subsequent release, the molecular details of this mechanism are not completely understood. Here, we identified the synaptic vesicle protein synaptogyrin-3 as a DAT interacting protein using the split ubiquitin system. This interaction was confirmed through coimmunoprecipitation experiments using heterologous cell lines and mouse brain. DAT and synaptogyrin-3 colocalized at presynaptic terminals from mouse striatum. Using fluorescence resonance energy transfer microscopy, we show that both proteins interact in live neurons. Pull-down assays with GST (glutathione S-transferase) proteins revealed that the cytoplasmic N termini of both DAT and synaptogyrin-3 are sufficient for this interaction. Furthermore, the N terminus of DAT is capable of binding purified synaptic vesicles from brain tissue. Functional assays revealed that synaptogyrin-3 expression correlated with DAT activity in PC12 and MN9D cells, but not in the non-neuronal HEK-293 cells. These changes were not attributed to changes in transporter cell surface levels or to direct effect of the protein-protein interaction. Instead, the synaptogyrin-3 effect on DAT activity was abolished in the presence of the vesicular monoamine transporter-2 (VMAT2) inhibitor reserpine, suggesting a dependence on the vesicular DA storage system. Finally, we provide evidence for a biochemical complex involving DAT, synaptogyrin-3, and VMAT2. Collectively, our data identify a novel interaction between DAT and synaptogyrin-3 and suggest a physical and functional link between DAT and the vesicular DA system

    The molecular epidemiology of respiratory viruses in military trainees in Iran

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    Background: Military populations are more prone to respiratory infections worldwide. There is a dearth of research about the role of viral pathogens in the etiology of respiratory infections in military trainees in Iran. Hence, we aimed to investigate the molecular epidemiology and clinical symptoms of respiratory viruses among this population. Methods: This cross-sectional study was performed on 400 military trainees with symptoms of respiratory infection, referred to the military medical clinic center in the basic military training camp of the General Staff of the Armed Forces of the Islamic Republic of Iran. Nucleic acid extraction from the throat or nasopharyngeal swab samples was performed by an automated extraction system. The extracts were then analyzed by the CLARTƂĀ® PneumoVir array system for the detection of respiratory viruses. Results: All military trainees were male, aged between 18 and 57 years (mean: 21.69 years). Sore throat (75.5), rhinorrhea (63.2), cough (59.2), fever (59.2), and nasal congestion (50.5) were amongst the most common symptoms. Overall, viral pathogens were detected in a total count of 124 (31). The most commonly detected viruses were rhinovirus (7.2), respiratory syncytial virus A (7.2) and influenza B virus (6). Conclusion: This study was an important first step for understanding the etiological role of viral pathogens in respiratory infection among military trainees population in Iran. Our results indicated that rhinovirus, respiratory syncytial virus A and influenza B virus are important viral pathogens causing respiratory infection in military trainees, respectively. However, further multi-center studies with larger sample size are strongly recommended to confirm our findings. ƂĀ© Iran University of Medical Sciences

    Electrogram Patterns Associated with Successful Radiofrequency Ablation of Accessory Pathways in Children

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    Electrograms observed prior to successful and unsuccessful ablation trials in 33 patients (362 attempts) with manifest pathways and 18 patients (194 attempts) with concealed pathways were compared to identify the electrogram patterns that are associated with successful radiofrequency ablation of accessory atrioventricular connections in young patients (mean age 12.7 years; range 4ā€“22 years). Success was defined as permanent or transient interruption of conduction in the accessory connection. Predictors of success in patients with manifest pathways were local ventricular preexcitation ( p = 0.0001), left-sidedness (43 or 174) of the accessory connection compared ( p = 0.04) to right-sidedness (27 of 172), a probable Kent bundle potential (29 of 84 versus 39 of 256; p = 0.0001), and short antegrade atrioventricular conduction intervals (53.1 Ā± 31.9 ms versus 64.6 Ā± 32.0 ms; p = 0.02). Predictors of success in patients with concealed pathways were short ventriculoatrial conduction times (103.3 Ā± 35.8 ms versus 117.9 Ā± 34.8 ms; p = 0.01), and left-sided (42 of 125) pathways ( p = 0.03; versus right-sided, 11 of 60). The presence of a Kent bundle potential was not significant. We conclude that specific electrogram patterns can predict successful ablation of either manifest or concealed accessory pathways. Use of these criteria may reduce the delivery of unnecessary energy to young myocardium.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42377/1/246-17-3-137_17n3p137.pd

    MRI-based contrast clearance analysis shows high differentiation accuracy between radiation-induced reactions and progressive disease after cranial radiotherapy

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    BACKGROUND: Pseudoprogression (PsP) or radiation necrosis (RN) may frequently occur after cranial radiotherapy and show a similar imaging pattern compared with progressive disease (PD). We aimed to evaluate the diagnostic accuracy of magnetic resonance imaging-based contrast clearance analysis (CCA) in this clinical setting. PATIENTS AND METHODS: Patients with equivocal imaging findings after cranial radiotherapy were consecutively included into this monocentric prospective study. CCA was carried out by software-based automated subtraction of imaging features in late versus early T1-weighted sequences after contrast agent application. Two experienced neuroradiologists evaluated CCA with respect to PsP/RN and PD being blinded for histological findings. The radiological assessment was compared with the histopathological results, and its accuracy was calculated statistically. RESULTS: A total of 33 patients were included; 16 (48.5%) were treated because of a primary brain tumor (BT), and 17 (51.1%) because of a secondary BT. In one patient, CCA was technically infeasible. The accuracy of CCA in predicting the histological result was 0.84 [95% confidence interval (CI) 0.67-0.95; one-sided PĀ = 0.051; nĀ = 32]. Sensitivity and specificity of CCA were 0.93 (95% CI 0.66-1.00) and 0.78 (95% CI 0.52-0.94), respectively. The accuracy in patients with secondary BTs was 0.94 (95% CI 0.71-1.00) and nonsignificantly higher compared with patients with primary BT with an accuracy of 0.73 (95% CI 0.45-0.92), PĀ = 0.16. CONCLUSIONS: In this study, CCA was a highly accurate, easy, and helpful method for distinguishing PsP or RN from PD after cranial radiotherapy, especially in patients with secondary tumors after radiosurgical treatment

    In vivo multiphoton imaging reveals gradual growth of newborn amyloid plaques over weeks

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    The kinetics of amyloid plaque formation and growth as one of the characteristic hallmarks of Alzheimerā€™s disease (AD) are fundamental issues in AD research. Especially the question how fast amyloid plaques grow to their final size after they are born remains controversial. By long-term two-photon in vivo imaging we monitored individual methoxy-X04-stained amyloid plaques over 6Ā weeks in 12 and 18Ā months old Tg2576 mice. We found that in 12Ā months old mice, newly appearing amyloid plaques were initially small in volume and subsequently grew over time. The growth rate of plaques was inversely proportional to their volume; thus amyloid plaques that were already present at the first imaging time point grew over time but slower compared to new plaques. Additionally, we analyzed 18Ā months old Tg2576 mice in which we neither found newly appearing plaques nor a significant growth of pre-existing plaques over 6Ā weeks of imaging. In conclusion, newly appearing amyloid plaques are initially small in size but grow over time until plaque growth can not be detected anymore in aged mice. These results suggest that drugs that target plaque formation should be most effective early in the disease, when plaques are growing
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