4,531 research outputs found

    Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C.

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    VLGR1 (very large G protein-coupled receptor 1), also known as MASS1 (monogenic audiogenic seizure susceptible 1), is an orphan G protein-coupled receptor that contains a large extracellular N terminus with 35 calcium-binding domains. A truncating mutation in the Mass1 gene causes autosomal recessive, sound-induced seizures in the Frings mouse. However, the function of MASS1 and the mechanism underlying Frings mouse epilepsy are not known. Here, we found that MASS1 protein is enriched in the myelinated regions of the superior and inferior colliculi, critical areas for the initiation and propagation of audiogenic seizures. Using a panel of myelin antibodies, we discovered that myelin-associated glycoprotein (MAG) expression is dramatically decreased in Frings mice. MASS1 inhibits the ubiquitylation of MAG, thus enhancing the stability of this protein, and the calcium-binding domains of MASS1 are essential for this regulation. Furthermore, MASS1 interacts with Gαs/Gαq and activates PKA and PKC in response to extracellular calcium. Suppression of signaling by MASS1 RNAi or a specific inhibitor abrogates MAG up-regulation. We postulate that MASS1 senses extracellular calcium and activates cytosolic PKA/PKC pathways to regulate myelination by means of MAG protein stability in myelin-forming cells of the auditory pathway. Further work is required to determine whether MAG dysregulation is a cause or consequence of audiogenic epilepsy and whether there are other pathways regulated by MASS1

    MicroRNA-23a promotes myelination in the central nervous system.

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    Demyelinating disorders including leukodystrophies are devastating conditions that are still in need of better understanding, and both oligodendrocyte differentiation and myelin synthesis pathways are potential avenues for developing treatment. Overexpression of lamin B1 leads to leukodystrophy characterized by demyelination of the central nervous system, and microRNA-23 (miR-23) was found to suppress lamin B1 and enhance oligodendrocyte differentiation in vitro. Here, we demonstrated that miR-23a-overexpressing mice have increased myelin thickness, providing in vivo evidence that miR-23a enhances both oligodendrocyte differentiation and myelin synthesis. Using this mouse model, we explored possible miR-23a targets and revealed that the phosphatase and tensin homologue/phosphatidylinositol trisphosphate kinase/Akt/mammalian target of rapamycin pathway is modulated by miR-23a. Additionally, a long noncoding RNA, 2700046G09Rik, was identified as a miR-23a target and modulates phosphatase and tensin homologue itself in a miR-23a-dependent manner. The data presented here imply a unique role for miR-23a in the coordination of proteins and noncoding RNAs in generating and maintaining healthy myelin

    Web Services for forward integration in international tourism supply chains: A case study of tourism in Thailand

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    International tourism is a highly competitive and information-intensive industry. Customers need volumes of information for decision aids. Moreover, the decision-making processes are quite sensitive to the variables of personal preferences, the tourist industrial ecosystem, the legal regulations and political environments of destinations, the regional or global economic situations, the natural matters, and so on. Hence, the owners of tourism are motivated to upgrade the competitiveness of their businesses with information technologies. This paper intends to design the architecture of Web Services in international tourism, which can contribute to the forward integration in international tourism supply chains. First, the authors conduct an in-depth case study of a regional tour operator in Thailand. In the case study, we examine the strength, weakness, challenges visions, and strategic approaches of international tourism, and their relationships with the information systems in the tourist business. Then, this paper designs the architecture of Web Services in international tourism. The architecture is expected to improve the information transparency through the global tourism supply chain, construct business-to-business collaboration mechanism, provide efficient and effective information to tourists, and consequently contribute to forward integration in international tourism supply chains

    RESEARCH ON THE MARKETING AND PUBLIC RELATIONS EFFECT AND SPORT EVENT SATISFACTION OF THE TAIPEI 2017 UNIVERSIADE

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    The purpose of this study is to investigate the spectators’ marketing and public relations and sport event satisfaction with their participation in the Taipei 2017 Universiade. Meanwhile, based on the comparison of different personal background variables, this study compares the attractiveness and satisfaction of the spectators’ marketing and public relations recognition, marketing and public relations attitude, event planning and sport event services. A random sampling method is adopted in this study. Among spectators, university students of the Taipei 2017 Universiade are selected. A total of 700 questionnaires are distributed and 680 valid questionnaires are collected. The effective recovery rate is 97.14%. The research tool of this study is “Satisfaction scale of marketing and public relations effect and sport event satisfaction of the Taipei 2017 Universiade”. This study uses statistical methods such as descriptive statistics, independent sample t-tests, and so forth. The results of this study are: (1) In the Taipei 2017 Universiade, spectators have the highest attractiveness with “Internet” in “media tools” of marketing and public relations recognition, followed by the factor of “TV”; (2) In “marketing and public relations attitude” of the Taipei 2017 Universiade, “marketing and public relations present efforts and earnest of Taiwan” ranks the highest, followed by “marketing and public relations are impressed”; (3) In “sport event services” of the Taipei 2017 Universiade, “auditorium” ranks the highest, followed by “broadcast notification”; (4) There is no significant difference in the attractiveness and satisfaction among spectators with different personal background for “marketing and public relations recognition”, “marketing and public relations attitude”, and “sport event services” in the Taipei 2017 Universiade.  Article visualizations

    THE INFLUENCE OF TASK-BASED LANGUAGE TEACHING AND AUDIO-LINGUAL TEACHING APPROACH ON MANDARIN LANGUAGE LEARNING OUTCOMES

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    The aim of this study is to look into the influence of Task-based Language Teaching (TBLT) and audio-lingual teaching approaches on Malaysia tertiary level non-native Mandarin learners’ learning outcomes in the teaching of Mandarin as a global language. A quasi-experimental study was carried out on 43 Universiti Malaysia Kelantan students, where they were divided into two groups. Group A contained 21 students, while Group B had 22 students. The two groups were studied to compare the influence of the two different teaching approaches: TBLT (Group A) and audio-lingual teaching approach (Group B). Willis’ (2006) Task-based Learning Framework was applied as the teaching framework in Group A (TBLT), while dialogue memorisation was applied in Group B (audio-lingual teaching approach). The results of the teaching approaches were analysed using simulated oral test, where language fluency, language accuracy and language pronunciation were the elements the researcher looked into. The results of the findings showed that Group A indicated a drop in the learning outcomes’ mean score in the first cycle of the post-treatment test, but the condition changed in the second cycle post-treatment test and delayed post-treatment test, where the learning outcomes of Group A (TBLT) outperformed the control group’s (audio-lingual teaching approach). The finding of the research provides suggestions towards teachers to apply communicative task between non-native learners and native speakers to improve learners’ learning outcomes. It also advises teachers to apply TBLT in a longer term rather than in a short term.&nbsp

    Downregulated serum 14, 15-epoxyeicosatrienoic acid is associated with abdominal aortic calcification in patients with primary aldosteronism

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    Patients with primary aldosteronism (PA) have increased risk of target-organ damage, among which vascular calcification is an important indicator of cardiovascular mortality. 14, 15-Epoxyeicosatrienoic acid (14, 15-EET) has been shown to have beneficial effects in vascular remodeling. However, whether 14, 15-EET associates with vascular calcification in PA is unknown. Thus, we aimed to investigate the association between 14, 15-EET and abdominal aortic calcification (AAC) in patients with PA. Sixty-nine patients with PA and 69 controls with essential hypertension, matched for age, sex, and blood pressure, were studied. 14, 15-Dihydroxyeicosatrienoic acid (14, 15-DHET), the inactive metabolite from 14, 15-EET, was estimated to reflect serum 14, 15-EET levels. AAC was assessed by computed tomographic scanning. Compared with matched controls, the AAC prevalence was almost 1-fold higher in patients with PA (27 [39.1%] versus 14 [20.3%]; P=0.023), accompanied by significantly higher serum 14, 15-DHET levels (7.18±4.98 versus 3.50±2.07 ng/mL; P<0.001). Plasma aldosterone concentration was positively associated with 14, 15-DHET (β=0.444; P<0.001). Multivariable logistic analysis revealed that lower 14, 15-DHET was an independent risk factor for AAC in PA (odds ratio, 1.371; 95% confidence interval, 1.145–1.640; P<0.001), especially in young patients with mild hypertension and normal body mass index. In conclusion, PA patients exibited more severe AAC, accompanied by higher serum 14, 15-DHET levels. On the contrary, decreased 14, 15-EET was significantly associated with AAC prevalence in PA patients, especially in those at low cardiovascular risk
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