417 research outputs found

    Phosphocholine – an agonist of metabotropic but not of ionotropic functions of alpha9-containing nicotinic acetylcholine receptors

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    We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1beta from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1beta is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1beta release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing alpha9 and alpha10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of alpha9 subunits or heteromeric receptors containing alpha9 and alpha10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions

    Empirical Investigation on Agile Methods Usage: Issues Identified from Early Adopters in Malaysia

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    Agile Methods are a set of software practices that can help to produce products faster and at the same time deliver what customers want. Despite the benefits that Agile methods can deliver, however, we found few studies from the Southeast Asia region, particularly Malaysia. As a result, less empirical evidence can be obtained in the country making its implementation harder. To use a new method, experience from other practitioners is critical, which describes what is important, what is possible and what is not possible concerning Agile. We conducted a qualitative study to understand the issues faced by early adopters in Malaysia where Agile methods are still relatively new. The initial study involves 13 participants including project managers, CEOs, founders and software developers from seven organisations. Our study has shown that social and human aspects are important when using Agile methods. While technical aspects have always been considered to exist in software development, we found these factors to be less important when using Agile methods. The results obtained can serve as guidelines to practitioners in the country and the neighbouring regions

    Comparing HBV Viral Load in Serum, Cerumen, and Saliva and Correlation With HBeAg Serum Status in Patients With Chronic Hepatitis B Infection

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    Background: Hepatitis B is a disease that is prevalent worldwide and is responsible for 10 of the deaths that occur every year. The virus persists in 5 of infected adults and 90 of infected children and can cause chronic hepatitis. In addition to blood, the virus may also be present in other secretions. Transmission through saliva, sexual fluids, and urine has also been confirmed. Objectives: The main aim of this study was to compare viral DNA copies in the serum, cerumen, and saliva of patients with HBeAg levels in their sera. Patients and Methods: This was a cross-sectional study and subjects were selected by non-randomized methods. Serum, cerumen, and saliva samples were collected from 50 patients who were diagnosed with chronic hepatitis B about a year prior to the study. Enzyme-linked immunosorbent assay (ELISA) was performed to determine the presence of HBsAg and HBeAg in the gathered specimens. Viral DNA was extracted from specimens by using a Qiagen kit. The number of viral DNA copies was determined using a real-time polymerase chain reaction (PCR) assay. The study was performed in Ilam province in western Iran. Results: Twenty-eight percent of the patients were HBeAg positive. The average number of viral copies in serum, cerumen, and saliva was higher in women than in men, and a significant correlation was observed between the gender and average viral copies. However, no significant correlation was observed between viral copies present in the serum and cerumen with the age and gender of patients. In addition, no correlation was observed between serum HBeAg and viral copies present in serum, cerumen, and saliva. The correlation analysis confirmed a direct and definite correlation between viral DNA loads in the patients' serum and cerumen. Conclusions: A significant direct correlation was observed between the viral DNA copies present in patients' cerumen and serum. However, the correlation between saliva viral load with serum and cerumen viral load was very low and inverse. These findings suggest that the presence of the hepatitis B virus (HBV) in non-invasive specimens (such as cerumen and saliva) should also be evaluated when monitoring patients to determine the course of infection and disease

    (New) Bulgarian Enlighteners and Ambassadors? The Reinvention of National Identity in Times of Crisis

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    Drawing on empirical data from 37 Bulgarian students and young professionals in the UK, this article explores the intersection of the discourses produced by the European crises and migrants' national identity. In Bulgaria, the crisis narrative is embedded in the arguably never‐ending democratic transition, manifested in socio‐economic instability and political volatility. Simultaneously, “Brexit Britain” is enveloped in strong Eurosceptic sentiments, propelled by a combination of austerity measures and intensified Eastern European migratory flows. Both contexts subject Bulgarian migrants to stigmatizing representations. Looking at migrants' everyday practices, the data reveals that young Bulgarians draw on the related ideas of the “new” Enlightener and Ambassador to counterbalance negative discourses. Thus, the article explores the meanings and significance attributed to the Enlighteners and the Ambassadors, arguing that the participants engage in “social creativity” and “individual mobility” strategies that lead to reinvention of national identity
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