Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation

Copyright © 2010 the authorsBrain-derived neurotrophic factor (BDNF) signaling is critical for neuronal development and transmission. Recruitment of TrkB receptors to lipid rafts has been hown to be necessary for the activation of specific signaling pathways and modulation of neurotransmitter release by BDNF. Since TrkB receptors are known to be modulated by adenosine A2A receptor activation, we hypothesized that activation of A2A receptors could influence TrkB receptor localization among different membrane microdomains. We found that adenosine A2A receptor agonists increased the levels of TrkB receptors in the lipid raft fraction of cortical membranes and potentiated BDNF-induced augmentation of phosphorylated TrkB levels in lipid rafts. Blockade of the clathrin-mediated endocytosis with monodansylcadaverine(100µM) did not modify the effects of theA2A receptor agonists but significantly impairedBDNFeffects on TrkB recruitment to lipid rafts. The effect of A2A receptor activation in TrkB localization was mimicked by 5 µM forskolin, an adenylyl cyclase activator. Also, it was blocked by the PKA inhibitors Rp-cAMPs and PKI-(14 –22), and by the Src-family kinase inhibitor PP2. Moreover, removal of endogenous adenosine or disruption of lipid rafts reduced BDNF stimulatory effects on glutamate release from cortical synaptosomes. Lipid raft integrity was also required for the effects of BDNF on hippocampal long-term potentiation at CA1 synapses. Our data demonstrate, for the first time, a BDNF-independent recruitment of TrkB receptors to lipid rafts induced by activation of adenosine A2A receptors, with functional consequences for TrkB phosphorylation and BDNF-induced modulation of neurotransmitter release and hippocampal plasticity.Supported by Fundacão para a Ciência e a Tecnologia (SFRH/BD/21374/2005 for N.A.L., SFRH/BD/21359/2005 for V.C.S., and SFRH/BPD/11528/2002 for D.B.P.) and by the European Union [European Cooperation in Science and Technology (COST) COST B30 concerted action, Neural Regeneration and Plasticity (NEREPLAS)]

Non-relativistic quantum systems on topological defects space-times

We study the behavior of non-relativistic quantum particles interacting with different potentials in the space-times generated by a cosmic string and a global monopole. We find the energy spectra in the presence of these topological defects and show how they differ from their free space-time values.Comment: 17 pages, LATEX fil

Exploring the outcomes of digital marketing on historic sites' visitor behaviour

Purpose – Digital communication and social media have an increasing importance in society and in tourism boosting. This study aims to analyse the role of digital marketing in the destination image and visitor loyalty of historic sites. Design/methodology/approach – Using a mixed-method approach combining survey data from 318 respondents and three in-depth interviews. Using structural equations modelling results reveals experience, satisfaction, image and loyalty are concepts to be considered by the destinations’ digital marketing promotion, as well as the increasing use of digital marketing by tourists, in the sense that tourists are increasing the habit of checking the opinion of others before scheduling their trip and gives them more importance, and a growing importance is given by tourists to the web/social networks of places they intend to visit. Findings – This study contributes to the theory on tourism digital marketing which can be transposed to organizations management in order to encourage discussion on the processes of capture, retention and loyalty of target audiences. Research limitations/implications – To enhance the importance of digital marketing in the process of the tourist development of the city, it is fundamental to define a clear strategy for attracting and responding to the greatest demand from cultural tourists who are increasingly interested in actively participating in learning experiences. Practical implications – The results show that digital communication and social media have an increasing importance in society and in tourism boosting and economy recovery. Social implications – The paper presents digital marketing as a possible factor in tourism development and social inclusion, advancing practical measures aimed at social justice through a fairer distribution of tourism revenues and the defence of historic centre residents’ way (i.e. Barcelos’), and quality of life. Originality/value – The authors suggest the development of a strategic digital marketing plan applied to the development and promotion of tourism in the city of Barcelos (Portugal), to complement the research presented here, thus contributing with a more practical perspective of the subject under study.info:eu-repo/semantics/acceptedVersio

Aplicações da espectroscopia de RMN (CWFP) na medida de umidade em sementes e grãos.

Neste trabalho demonstramos as vantagens e desvantagens de se usar a técnica de CWFP para medidas de óleo e umidade em sementes, em relação as técnicas normais de RMN com o uso do FID e eco.bitstream/CNPDIA/8115/1/CiT14_2002.pd

Dermoscopic and Reflectance Confocal Microscopic Presentation of Hailey‐Hailey Disease: a Case Series

Background/purpose: Hailey-Hailey disease is a rare inherited acantholytic skin disorder characterized by heterogeneous clinical presentation. Its differential diagnosis might be wide, including other genodermatoses, inflammatory, and infectious skin diseases. Although histopathology remains as diagnostic gold standard, noninvasive techniques such as dermoscopy and reflectance confocal microscopy may assist clinical examination. Herein, we aim to further characterize the dermoscopic and reflectance confocal microscopic presentation of Hailey-Hailey disease with histologic correlation. Methods: Eight patients with Hailey-Hailey disease were consecutively recruited. All patients were examined using dermoscopy and reflectance confocal microscopy. Results: In all cases, dermoscopy enabled the visualization of polymorphous vessels, including glomerular and linear-looped vessels, within a pink-whitish background. Reflectance confocal microscopy revealed wide suprabasilar partial acantholysis and clefting, crusts, dilated papillae with tortuous vessels, and inflammatory cells. Dyskeratosis, uplocated papillae, and adnexal sparing were also observed. Conclusion: Although definite diagnosis was obtained by histopathology in all cases, dermoscopy and reflectance confocal microscopy allowed the identification of common features (even in cases with dissimilar clinical presentation) that may support an early diagnosis of Hailey-Hailey disease, and its differentiation from other more frequent skin disorders.info:eu-repo/semantics/publishedVersio

THYMUS-DEPENDENT AREAS IN THE LYMPHOID ORGANS OF NEONATALLY THYMECTOMIZED MICE

Specific areas of lymphocyte depletion, termed thymus-dependent areas, have been delineated in neonatally thymectomized C3H/Bi and F1 (C57BL x C3H/Bi) mice. They occur within the lymphoid follicles of the spleen immediately surrounding the central arterioles, and constitute the mid and deep cortical zones of the lymph nodes. These depleted areas appear in healthy thymectomized mice as early as 3 wk after operation but, in mice which survive for more than 6 to 7 wk, the thymus-dependent areas are repopulated by rapidly dividing pyroninophilic cells, the majority of which are immature plasma cells. Syngeneic thymus cells, labeled in vitro with tritiated adenosine localize preferentially in the thymus-dependent areas after intravenous injection. Similarly labeled spleen cells also accumulate in these areas but, in addition, are distributed at the periphery of splenic follicles and in the outer cortical zone of the lymph nodes. Many more spleen than thymus cells enter the lymphoid tissues and the spleen appears to be the primary target. The apparent paradox that syngeneic thymus cells are less efficient than spleen cells in restoring neonatally thymectomized mice to normality is discussed in the light of these results and possible routes by which the migrating cells could enter the lymphoid tissues are considered. The origin of the plasma cells which repopulate the lymphocyte depleted areas is also discussed. It is concluded that the normal thymus produces cells which contribute directly to the migratory or circulatory lymphocyte population but that there also exists another source of supply for the plasma cell series. These two systems may function synergistically so that the thymus may control, directly or indirectly, the balance of cell populations within the body