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)]

Experimental Study of a Single Droplet Impinging Upon a Heated Dry Surface Using Jet Fuel and Biofuel Mixtures

The aeronautical sector is dependent on fossil fuels which contribute to a considerable amount of pollutant emissions to the atmosphere. In an attempt to reduce these pollutant emissions in a short period of time and without several changes to the aircraft and their engines, this study focuses on the physical phenomena that happen inside the combustion chamber of an internal combustion engine during fuel injection. However, instead of considering only a conventional jet fuel, an alternative fuel is also investigated. The mixture is composed of at least 50% in volume of conventional jet fuel, as demanded by the current legislation, and a biofuel to decrease the consumption of petroleum-based fuels and to reduce pollutant emissions. The main goal of this study is to experimentally observe droplet impact on a heated dry stainless-steel surface for different fuel mixtures, impact energies (Weber number between 174 and 955, and Reynolds number between 1099 and 12365), and wall temperatures (Tw = 20 − 300 ºC) to identify the different heat regimes and the physical differences between the distinct sets of impact conditions. To achieve that purpose an experimental setup was designed and built including the acquisition of high-speed images, a droplet dispensing system, a heating device to accurately control the temperature of the target surface and the illumination of the impact site. To enhance the knowledge about the impacts, three different perspectives of the phenomena were captured. The typical front perspective, a second perspective where the camera has a ≈ 20◦ angle to the impact surface to capture more details of the impact, and finally, at a lower frame rate, an isometric perspective to measure the evaporation time. From these data, the impact regimes were identified and the influence of surface temperature, fluid properties, and impact energy was analyzed.Fundação para a Ciência e a Tecnologiainfo:eu-repo/semantics/publishedVersio

Modificação de betumes com aditivos líquidos para aplicação em países tropicais

A modificação de betumes é uma das soluções mais utilizadas na pavimentação, sobretudo em países com climas quentes, pois permite minimizar problemas tais como o fendilhamento, o envelhecimento do betume, e em especial as deformações permanentes. Este trabalho visa estudar uma solução para modificação do betume de modo a contornar os problemas acima indicados do betume puro existente nesses países. Para isso foram utilizados dois aditivos líquidos, SBR líquido e ácido polifosfórico (PPA), e foram estudadas diferentes percentagens de adição dos mesmos em betumes puros, de modo a selecionar o aditivo com mais potencial e a percentagem em que devia ser incorporado.Fundos QREN, através da ANI, no âmbito do projeto Tropical-Pav – “Soluções de Pavimentação Rodoviária para Climas Tropicais”, num consórcio constituído por duas empresas e quatro entidades do Sistema Científico e Tecnológico Nacional (SCTN), nomeadamente Elevo Grupo, Mota-Engil Engenharia e Construção, Instituto Superior Técnico, Laboratório Nacional de Engenharia Civil, Universidade de Coimbra e Universidade do Minho

Insights on bubble encapsulation after drop impact on thin liquid films

The accurate understanding of the phenomenology of drop impact onto dry/ wetted and cold/heated surfaces is increasingly relevant to implement biofuels in civil aviation. The outcome of drop impact depends on the pre-impact conditions and a seldom researched event is the encapsulation of a bubble when this impact occurs on thin liquid films. Therefore, the goal of the experimental work reported is to investigate the mechanism of this bubble encapsulation. Results show that the mechanism leading to a bubble formation has two stages. In the first stage, after the drop impacts a steady liquid film, a prompt splash occurs followed by a crown splash. The uprising sheet propagates in an almost normal direction relative to the liquid film, but its radius at the base continues to expand, eventually leading to the inward collapse of the crown-bounding rim encapsulating air inside the dome. In the second stage, three different phenomenologies of bubble encapsulation can occur. At the top of the closed crown, one jet (phenomenology 1) or two jets are formed (phenomenologies 2 and 3). For phenomenology 2, the upward jet eventually collapses due to gravitational influence, while the downward jet continues to grow until it reaches the liquid film, attaching to it, stretching and detaching from the top at the hemispheric thin sheet, forming a bubble. In phenomenology 3, the upward jet is high enough to allow its breakup and ejection of one large droplet before the collapse of the upward jet. Many secondary droplets fall on the bubble and one of them will eventually break the dome, leading to more secondary atomization. Additionally, the first perturbation imposed on the liquid film by the droplet impact is studied and an empirical correlation is proposed for its propagation velocity. Finally, bubble geometry is investigated.Fundação para a Ciência e a Tecnologiainfo:eu-repo/semantics/publishedVersio

Analysis And Visualization Of The Perturbations Imposed On The Liquid Film By Crown Sheet Collapse Or Closure

Bubble encapsulation is a phenomenon that results from droplet impact on a liquid film for very specific impact conditions. After splashing, the crown liquid sheet starts to bend inwards, and eventually, the jets at the top of the crown merge and form a perfect empty bubble. This bubble bursts due to the impingement of a secondary droplet that falls in the spherical dome or by reaching its critical thickness. However, bubble encapsulation is seldom reported in the literature. Due to that, this work focuses on understanding better its dynamics and formation mechanisms. By using a bottom perspective of the phenomenon, important information about its dynamics is disclosed. From the bottom shadowgraphs, the capillary waves and the perturbations imposed on the steady liquid film are clearly observed. From previous works, it was confirmed that its occurrence is systematic, so, one of the goals of this study is to realize how the impact conditions influence the phenomenon and if we can establish a criterion for its occurrence. Despite the scarce information about the phenomenon, there are some works about it that are focused on the cavity underneath the bubble. In this study, we observed the cavity and conclude that the cavity shape does not influence the bubble encapsulation phenomenon. Finally, the crown closure time was measured for a specific set of impact conditions and it was analyzed depending on the dimensionless thickness of the liquid film.Fundação para a Ciência e a Tecnologiainfo:eu-repo/semantics/publishedVersio

Insights on Bubbling Formation after Drop Impact on Thin Liquid Films

Over the years, the phenomena obtained when a drop impinges upon a dry, wetted or heated surface have been thoroughly studied. In previous works, the existence of splash was investigated by the authors with the goal of evaluating the possible implementation of biofuels in the civil aviation and it was found an episode of a phenomenon, seldom reported in the literature under specific pre-impingement conditions. The mechanism that leads to a bubble formation has two stages. After the drop impacts a steady liquid film, prompt splash occurs followed by crown splash. In the first stages of crown splash, the uprising sheet propagates almost normal to the liquid film, but its radius at the base continues to expand, eventually leading to the inward collapse of the crown bounding rim. Thus, the top of the crown closes in a bubble-like shape with the formation of two jets, one upwards and other downwards. The upward jet eventually disappears due to gravitational influence, while the downward jet continues to grow until it reaches the liquid film, attaching to it, stretching and detaching from the top at the hemispheric thin-sheet, forming a perfect bubble. Many secondary droplets fall on the bubble and one of them will eventually break the dome, leading to more secondary atomization. The few works reported in the literature referring to this phenomenon as “bubbling” or “floating bubble,” scarcely explore the hydrodynamic mechanism associated with this bubble formation and occurrence, mainly focusing on droplets impacting upon deep pools. However, in a previous study, the authors observed this event for a liquid film dimensionless thickness of 0:5 in a fluid mixture of Jet A-1 and biofuel NEXBTL. In this study, the impact conditions in the experiments performed allow to recreate the floating bubble with 100% of occurrence. After that, the authors present an extensive characterization of the bubbling phenomenon to understand better the mechanisms which lead to its formation, as well as its practical significance. A high-speed digital camera acquires several images of the floating bubble formation from different points of view (side and bottom). Namely, capturing the phenomenon from below, high-quality images allow retrieving essential data to describe the hydrodynamic mechanism accurately. The most relevant features include the bubble height and diameter, and the propagation velocity of the first perturbation imposed on the liquid film.info:eu-repo/semantics/publishedVersio

Dibucaine in Ionic-Gradient Liposomes: Biophysical, Toxicological, and Activity Characterization

Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 μM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of dibucaine.Fil: Couto, Verônica M.. Universidade Estadual de Campinas; BrasilFil: Prieto, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Igartúa, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Feas, Daniela Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: Ribeiro, Lígia N.M.. Universidade Estadual de Campinas; BrasilFil: Silva, Camila M.G.. Universidade Estadual de Campinas; BrasilFil: Castro, Simone R.. Universidade Estadual de Campinas; BrasilFil: Guilherme, Viviane A.. Universidade Estadual de Campinas; BrasilFil: Dantzger, Darlene D.. Universidade Estadual de Campinas; BrasilFil: Machado, Daisy. Universidade Estadual de Campinas; BrasilFil: Alonso, Silvia del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB | Universidad Nacional de la Plata. Instituto Multidisciplinario de Biología Celular. Grupo Vinculado al IMBICE - Grupo de Biología Estructural y Biotecnología-Universidad Nacional de Quilmes - GBEyB; ArgentinaFil: de Paula, Eneida. Universidade Estadual de Campinas; Brasi

A study of droplet deformation: The effect of crossflow velocity on jet fuel and biofuel droplets impinging onto a dry smooth surface

The aeronautical sector has been, in the last decade, one of those that most invested in more efficient and ecological solutions in order to reduce significantly greenhouse gas and pollutant emissions. The introduction of biofuels in fuel mixtures for aircraft engines is a promising alternative in this sector. The main objective of this experimental study is understanding the influence of crossflow variation on droplet deformation and consequent impact outcomes. An experimental facility was developed and validated to study the impact of single droplets onto a dry, smooth aluminium impact surface under the influence of several crossflow velocities. Different crossflow velocities of 4,5,6,7 and 8m/s were tested. A combination of conventional jet fuel and a biofuel was considered to understand the behavior of jet fuel and biofuel mixtures, and three fluids were used: 100% jet fuel, 75% jet fuel/25% biofuel and 50% jet fuel/50% biofuel. Several parameters, including velocity components, impact angle and eccentricity, were analysed for the different crossflow velocities, and the spread and splash regimes were also defined for the different fluids. The results display that, for each crossflow velocity, an increase in the droplet impact velocity causes a shift from the spread to the splash regime. The presence of a crossflow induces deformation on the droplet, altering its outcome. Ellipsoidal droplets promote the occurrence of spreading, whereas splashing tends to occur for spherical forms, corresponding to higher and lower eccentricity values, respectively. A substantial increase in the crossflow velocity leads to aerodynamic breakup of the droplet.Fundação para a Ciência e a Tecnologiainfo:eu-repo/semantics/publishedVersio

Oromucosal Alginate Films with Zein Nanoparticles as a Novel Delivery System for Digoxin

Digoxin is a hydrophobic drug used for the treatment of heart failure that possesses a narrow therapeutic index, which raises safety concerns for toxicity. This is of utmost relevance in specific populations, such as the elderly. This study aimed to demonstrate the potential of the sodium alginate films as buccal drug delivery system containing zein nanoparticles incorporated with digoxin to reduce the number of doses, facilitating the administration with a quick onset of action. The film was prepared using the solvent casting method, whereas nanoparticles by the nanoprecipitation method. The nanoparticles incorporated with digoxin (0.25 mg/mL) exhibited a mean size of 87.20 ± 0.88 nm, a polydispersity index of 0.23 ± 0.00, and a zeta potential of 21.23 ± 0.07 mV. Digoxin was successfully encapsulated into zein nanoparticles with an encapsulation efficiency of 91% (±0.00). Films with/without glycerol and with different concentrations of ethanol were produced. The sodium alginate (SA) films with 10% ethanol demonstrated good performance for swelling (maximum of 1474%) and mechanical properties, with a mean tensile strength of 0.40 ± 0.04 MPa and an elongation at break of 27.85% (±0.58), compatible with drug delivery application into the buccal mucosa. The current study suggests that SA films with digoxin-loaded zein nanoparticles can be an effective alternative to the dosage forms available on the market for digoxin administration