Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors

© 1998 Society for NeuroscienceATP analogs substituted in the γ-phosphorus (ATPγS, β, γ-imido-ATP, and β, γ-methylene-ATP) were used to probe the involvement of P2 receptors in the modulation of synaptic transmission in the hippocampus, because their extracellular catabolism was virtually not detected in CA1 slices. ATP and γ-substituted analogs were equipotent to inhibit synaptic transmission in CA1 pyramid synapses (IC50 of 17–22 μM). The inhibitory effect of ATP and γ-phosphorus-substituted ATP analogs (30 μM) was not modified by the P2 receptor antagonist suramin (100 μM), was inhibited by 42–49% by the ecto-5’- nucleotidase inhibitor and α, β-methylene ADP (100 μM), was inhibited by 74–85% by 2 U/ml adenosine deaminase (which converts adenosine into its inactive metabolite-inosine), and was nearly prevented by the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10 nM). Stronger support for the involvement of extracellular adenosine formation as a main requirement for the inhibitory effect of ATP and γ-substituted ATP analogs was the observation that an inhibitor of adenosine uptake, dipyridamole (20 μM), potentiated by 92–124% the inhibitory effect of ATP and γ-substituted ATP analogs (10 μM), a potentiation similar to that obtained for 10 μM adenosine (113%). Thus, the present results indicate that inhibition by extracellular ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ectonucleotidases and channeling of the generated adenosine to adenosine A1 receptors.This work was supported by Junta Nacional de Investigação Cientifica e Tecnológica, Praxis XXI, Gulbenkian Foundation, and European Union (BIOMED 2 programme

Caffeine and adenosine

© 2010 – IOS Press and the authors. All rights reservedCaffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine.The work in the authors’ laboratory is supported by research grants from Fundação para a Ciência e Tecnologia (FCT), Gulbenkian Foundation and European Union (COST B30)

Pricing of project finance bonds: a comparative analysis of primary market spreads

This paper provides a comparative analysis of project finance (PF) and traditional corporate finance (CF) bond spreads and pricing. Using a cross-section of 47,196 bonds issued worldwide in the 1993–2020 period, we show that PF and CF bonds are differently priced, PF bonds have higher spreads than comparable CF bonds, and although ratings are the most important pricing determinant for PF and CF bonds at issuance, investors rely on other contractual, macroeconomic, and firms' characteristics beyond these ratings. Our results do not support the hypothesis of PF transactions as mechanisms of reducing sponsoring firms' funding costs: the cost of borrowing affects financing choices and PF transactions' weighted average spread is higher than that of comparable CF bond deals. We also find that economies of scale, risk management, and information asymmetry arguments affect sponsoring firms' choice between PF and CF transactions.N/

On the role of stigmergy in cognition

Cognition in animals is produced by the self- organized activity of mutually entrained body and brain. Given that stigmergy plays a major role in self-organization of societies, we identify stigmergic behavior in cognitive systems, as a common mechanism ranging from brain activity to social systems. We analyze natural societies and artificial systems exploiting stigmergy to produce cognition. Several authors have identified the importance of stigmergy in the behavior and cognition of social systems. However, the perspective of stigmergy playing a central role in brain activity is novel, to the best of our knowledge. We present several evidences of such processes in the brain and discuss their importance in the formation of cognition. With this we try to motivate further research on stigmergy as a relevant component for intelligent systems.info:eu-repo/semantics/acceptedVersio

Self-reported knowledge, experiences and predisposition towards interprofessional education and collaborative practice in faculty members from the centre-west region of Brazil: a qualitative study

The mechanisms that facilitate interprofessional education and collaborative practice (IPECP) associated with the academic training project include the effective involvement of faculty members, a topic about which there is little available knowledge in Portuguese speaking countries. The goal of the present study was the understanding of self-reported knowledge, experiences, and willingness towards IPECP of health/related areas professors, from two universities in the centre-west region of Brazil. The intentional sample included 16 professors, members of the College and Teaching Structuring Cores (definition, management and update of undergraduate pedagogical projects), who answered a semi structured interview script and filled in a sociodemographic and professional profile questionnaire. The interviews were transcribed verbatim, validated by the participants and then submitted to a thematic content analysis, supported by NVivo, version 11. The resultsrevealed six inductive thematic categories (Undergraduate Training Process, Professional Experience in IPECP, Mechanisms for IPECP, Openness to IPECP, Interprofessional Relations and Representation of IPECP), and 24 subcategories. In general, participants revealed to be open to IPECP, even though not all had knowledge of the mechanisms or technical, political, and ethical tools that favour the development of IPECP, in undergraduate degrees

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)]

Amyotrophic Lateral Sclerosis ALS and adenosine receptors

Copyright © 2018 Sebastião, Rei and Ribeiro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.In the present review we discuss the potential involvement of adenosinergic signaling, in particular the role of adenosine receptors, in amyotrophic lateral sclerosis (ALS). Though the literature on this topic is not abundant, the information so far available on adenosine receptors in animal models of ALS highlights the interest to continue to explore the role of these receptors in this neurodegenerative disease. Indeed, all motor neurons affected in ALS are responsive to adenosine receptor ligands but interestingly, there are alterations in pre-symptomatic or early symptomatic stages that mirror those in advanced disease stages. Information starts to emerge pointing toward a beneficial role of A2A receptors (A2AR), most probably at early disease states, and a detrimental role of caffeine, in clear contrast with what occurs in other neurodegenerative diseases. However, some evidence also exists on a beneficial action of A2AR antagonists. It may happen that there are time windows where A2AR prove beneficial and others where their blockade is required. Furthermore, the same changes may not occur simultaneously at the different synapses. In line with this, it is not fully understood if ALS is a dying back disease or if it propagates in a centrifugal way. It thus seems crucial to understand how motor neuron dysfunction occurs, how adenosine receptors are involved in those dysfunctions and whether the early changes in purinergic signaling are compensatory or triggers for the disease. Getting this information is crucial before starting the design of purinergic based strategies to halt or delay disease progression.This work was supported by LISBOA-01-0145-FEDER-007391, project co-funded by FEDER through POR Lisboa 2020 (Programa Operacional Regional de Lisboa) from PORTUGAL 2020 and Fundação para a Ciência e Tecnologia (FCT) and by a Twinning action (SynaNet) from the EU H2020 program (Project Number: 692340). NR is in receipt of an FCT fellowship (PD /BD/113463/2015) and is a fellow of the M2B-Ph.D. Program.info:eu-repo/semantics/publishedVersio

On the Renormalizability of Theories with Gauge Anomalies

We consider the detailed renormalization of two (1+1)-dimensional gauge theories which are quantized without preserving gauge invariance: the chiral and the "anomalous" Schwinger models. By regularizing the non-perturbative divergences that appear in fermionic Green's functions of both models, we show that the "tree level" photon propagator is ill-defined, thus forcing one to use the complete photon propagator in the loop expansion of these functions. We perform the renormalization of these divergences in both models to one loop level, defining it in a consistent and semi-perturbative sense that we propose in this paper.Comment: Final version, new title and abstract, introduction and conclusion rewritten, detailed semiperturbative discussion included, references added; to appear in International Journal of Modern Physics

Hábitos alimentares de utentes adultos do centro de saúde de Castelo Branco

Em Portugal têm vindo a revelar-se alguns erros alimentares praticados por grande parte da população. Esses erros cometem-se por excesso de ingestão de certo tipo de alimentos que, consequentemente, levam a problemas no organismo, como é o caso da obesidade, diabetes, hipertensão arterial, entre outras doenças