HDAC6 is a bruchpilot deacetylase that facilitates neurotransmitter release

Presynaptic densities are specialized structures involved in synaptic vesicle tethering and neurotransmission; however, the mechanisms regulating their function remain understudied. In Drosophila, Bruchpilot is a major constituent of the presynaptic density that tethers vesicles. Here, we show that HDAC6 is necessary and sufficient for deacetylation of Bruchpilot. HDAC6 expression is also controlled by TDP-43, an RNA-binding protein deregulated in amyotrophic lateral sclerosis (ALS). Animals expressing TDP-43 harboring pathogenic mutations show increased HDAC6 expression, decreased Bruchpilot acetylation, larger vesicle-tethering sites, and increased neurotransmission, defects similar to those seen upon expression of HDAC6 and opposite to hdac6 null mutants. Consequently, reduced levels of HDAC6 or increased levels of ELP3, a Bruchpilot acetyltransferase, rescue the presynaptic density defects in TDP-43-expressing flies as well as the decreased adult locomotion. Our work identifies HDAC6 as a Bruchpilot deacetylase and indicates that regulating acetylation of a presynaptic release-site protein is critical for maintaining normal neurotransmission

Espontaneidade e impulsividade: Definições, avaliação e relações mútuas

A espontaneidade é um constructo central na obra de Moreno. Apesar disso, persiste ainda hoje, alguma indefinição, a que não é alheia, não só a sua complexidade, como também, a dificuldade de avaliação pela investigação empírica. Por outro lado, existe também alguma falta de clareza quanto à sua relação com outros constructos, nomeadamente o de impulsividade. O objectivo deste estudo é avaliar a relação entre espontaneidade e impulsividade, contribuindo para o esclarecimento da sua distinção. A nossa hipótese foi a de que não existe relação estatisticamente significativa entre os níveis de espontaneidade e os de impulsividade. Os instrumentos utilizados para avaliar a espontaneidade e a impulsividade foram, respectivamente, o SAI-R (Kipper, 2005) e a sub-escala N-5 da dimensão Neuroticismo do NEO-PI (Costa & McCrae, 1989, versão portuguesa, Lima & Simões, 1997). Neste estudo participaram 90 sujeitos, com idades compreendidas entre 19 e os 65 anos, sendo a média 29 anos (M = 28.59, S.D. =10.99). A selecção dos participantes foi feita através do método de amostragem por conveniência. Os valores obtidos, apontando para a inexistência de uma relação estatisticamente significativa (p=0,063) entre os dois constructos, vieram, não só, confirmar a nossa hipótese de estudo como, também, proporcionam um suporte empírico à proposição teórica de Moreno no que diz respeito a esta questão.ABSTRACT: Spontaneity is a main construct in Moreno´s work. Nevertheless, some indefinition persist concerning, not only, its complexity, but also the difficulty in assessing it by empirical investigations. On the other hand, there´s also a lack of transparency in respect to it´s relations with other constructs, namely the one of impulsivity. The aim of this study is to assess the relation between spontaneity and impulsivity, helping to enlight the way to distinguish them. Our hypotesis is that there is not a statistically significant correlation between levels of spontaneity and of impulsivity. The SAI-R (Kipper, 2005) and the N5 scale of the Neuroticism dimension of the NEO-PI-R (Costa & McCrae, 1989, portuguese version, Lima & Simões, 1997) were administred to 90 individuals, the mean being 29 years old (M=28.59, S.D.=10.99). The participants were selected through convenient sampling. As expected, the results showed that there is no statistically significant correlation (p=0,063) between both constructs, giving empiric support to the theoretical proposition of Moreno concerning to this issue

Pharmacogenetic: screening relevant polymorphisms on antiretroviral therapy in a HIV Portuguese population

Poster presented at the 15th European AIDS Conference. Barcelona, 21-24 October 2015"Several factors cause heterogeneity of response to antiretroviral therapy. Genetic polymorphisms, particularly in metabolizing enzyme, cytochrome P450 isoenzymes and transport proteins MDR, MRP and SLC, may cause pharmacokinetic variability in some ARVs, leading to viral failure, drug toxicity and may explain the interpatient variability for drug absorption pathways.

Biodegradation assessment of a 16th century fresco from Southern Portugal

This work reports the study of the frescoes from the Casa de Fresco dos Sanches Baena in Vila Viçosa (Southeast Portugal) to allow their material characterisation, to identify the different populations of microorganisms and to assess their role in the deterioration of these paintings

Searching for the G516T Polymorphism on the CYP2B6 gene in HIV-1Patients

Poster presented at the International Young Researchers in Life Sciences Conference. Pasteur Institute, Paris, France, 26-28 May 2014

The Demise of Multidrug-Resistant HIV-1: the National Time Trend in Portugal

OBJECTIVES: Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal. PATIENTS AND METHODS: We used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR. RESULTS: We observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7-8.4) in 2001-03, 6.0% (95% CI: 4.9-7.2) in 2003-05, 3.7% (95% CI: 2.8-4.8) in 2005-07 and 1.6% (95% CI: 1.1-2.2) in 2007-09 down to 0.6% (95% CI: 0.3-0.9) in 2009-12 [OR=0.80 (95% CI: 0.75-0.86); P<0.001]. In July 2011 the last new case of MDR was seen. CONCLUSIONS: The prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.info:eu-repo/semantics/publishedVersio

Adenosine A(2A) receptor blockade reverts hippocampal stress-induced deficits and restores corticosterone circadian oscillation

Maternal separation (MS) is an early life stress model that induces permanent changes in the central nervous system, impairing hippocampal long-term potentiation (LTP) and spatial working memory. There are compelling evidences for a role of hippocampal adenosine A(2A) receptors in stress-induced modifications related to cognition, thus opening a potential window for therapeutic intervention. Here, we submitted rats to MS and evaluated the long-lasting molecular, electrophysiological and behavioral impairments in adulthood. We then assessed the therapeutic potential of KW6002, a blocker of A(2A) receptors, in stress-impaired animals. We report that the blockade of A(2A) receptors was efficient in reverting the behavior, electrophysiological and morphological impairments induced by MS. In addition, this effect is associated with restoration of the hypothalamic-pituitary-adrenal axis (HPA-axis) activity, as both the plasma corticosterone levels and hippocampal glucocorticoid receptor expression pattern returned to physiological-like status after the treatment. These results reveal the involvement of A(2A) receptors in the stress-associated impairments and directly in the stress response system by showing that the dysfunction of the HPA-axis as well as the long-lasting synaptic and behavioral effects of MS can be reverted by targeting adenosine A(2A) receptors. These findings provide a novel evidence for the use of adenosine A(2A) receptor antagonists as potential therapy against psychopathologiesWe acknowledge Alexandre de Mendonca, David Blum and Rodrigo Cunha for helpful discussions. VLB is thankful to Joao Baiao and Carla Batalha for technical assistance. VLB has been awarded a PhD fellowship from Fundacao para a Ciencia e Tecnologia (BD/63041/2009). LVL is funded by Fundacao para a Ciencia e Tecnologia (PTDC/SAU-NEU/099853/2008) and by EU programme Egide-Pessoa. YB and CEM were funded by the Ministry for Education and Research (BMBF, Grant number 01EW0911) in the frame of ERA-NET NEURON

Overexpression of Adenosine A2A receptors in rats: effects on depression, locomotion, and anxiety

Copyright: © 2014 Coelho, Alves, Canas, Valadas, Shmidt, Batalha, Ferreira, Ribeiro, Bader, Cunha, do Couto and Lopes. 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) or licensor 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.Adenosine A2A receptors (A2AR) are a sub-type of receptors enriched in basal ganglia, activated by the neuromodulator adenosine, which interact with dopamine D2 receptors. Although this reciprocal antagonistic interaction is well-established in motor function, the outcome in dopamine-related behaviors remains uncertain, in particular in depression and anxiety. We have demonstrated an upsurge of A2AR associated to aging and chronic stress. Furthermore, Alzheimer's disease patients present A2AR accumulation in cortical areas together with depressive signs. We now tested the impact of overexpressing A2AR in forebrain neurons on dopamine-related behavior, namely depression. Adult male rats overexpressing human A2AR under the control of CaMKII promoter [Tg(CaMKII-hA2AR)] and aged-matched wild-types (WT) of the same strain (Sprague-Dawley) were studied. The forced swimming test (FST), sucrose preference test (SPT), and the open-field test (OFT) were performed to evaluate behavioral despair, anhedonia, locomotion, and anxiety. Tg(CaMKII-hA2AR) animals spent more time floating and less time swimming in the FST and presented a decreased sucrose preference at 48 h in the SPT. They also covered higher distances in the OFT and spent more time in the central zone than the WT. The results indicate that Tg(CaMKII-hA2AR) rats exhibit depressive-like behavior, hyperlocomotion, and altered exploratory behavior. This A2AR overexpression may explain the depressive signs found in aging, chronic stress, and Alzheimer's disease.Joana E. Coelho, Vânia L. Batalha and Diana G. Ferreira were supported by a grant from Fundação para a Ciência e Tecnologia (FCT); Paula M. Canas and Rodrigo A. Cunha were supported by FCT (PTDC/SAU-NSC/122254/2010) and Defense Advanced Research Projects Agency (DARPA, grant 09-68-ESR- FP-010). Luísa V. Lopes is an Investigator FCT, funded by Fundação para a Ciência e Tecnologia (PTDC-099853/2009) and Bial.info:eu-repo/semantics/publishedVersio