MFS transporters required for multidrug/multixenobiotic (MD/MX) resistance in the model yeast: understanding their physiological function through post-genomic approaches

Multidrug/Multixenobiotic resistance (MDR/MXR) is a widespread phenomenon with clinical, agricultural and biotechnological implications, where MDR/MXR transporters that are presumably able to catalyze the efflux of multiple cytotoxic compounds play a key role in the acquisition of resistance. However, although these proteins have been traditionally considered drug exporters, the physiological function of MDR/MXR transporters and the exact mechanism of their involvement in resistance to cytotoxic compounds are still open to debate. In fact, the wide range of structurally and functionally unrelated substrates that these transporters are presumably able to export has puzzled researchers for years. The discussion has now shifted towards the possibility of at least some MDR/MXR transporters exerting their effect as the result of a natural physiological role in the cell, rather than through the direct export of cytotoxic compounds, and the hypothesis that MDR/MXR transporters may have evolved in nature for other purposes than conferring chemoprotection has been gaining momentum in recent years. This review focuses on the drug transporters of the Major Facilitator Superfamily (MFS; drug:H+ antiporters) in the model yeast Saccharomyces cerevisiae. New insights into the natural roles of these transporters are described and discussed here, focusing on the knowledge obtained or suggested by post-genomic research. The new information reviewed here provides clues into the unexpectedly complex roles of these transporters, including a proposed indirect regulation of the stress response machinery and control of membrane potential and/or internal pH, with a special emphasis on a genome-wide view of the regulation and evolution of MDR/MXR-MFS transporters

Visual contrast sensitivity in tonic-clonic epileptic patients

We measured the effects of epilepsy on visual contrast sensitivity to linear and vertical sine-wave gratings. Sixteen female adults, aged 21 to 50 years, comprised the sample in this study, including eight adults with generalized tonic-clonic seizure-type epilepsy and eight age-matched controls without epilepsy. Contrast threshold was measured using a temporal two-alternative forced-choice binocular psychophysical method at a distance of 150 cm from the stimuli, with a mean luminance of 40.1 cd/m². A one-way analysis of variance (ANOVA) applied to the linear contrast threshold showed significant differences between groups (F[3,188] = 14.829; p < .05). Adults with epilepsy had higher contrast thresholds (1.45, 1.04, and 1.18 times for frequencies of 0.25, 2.0, and 8.0 cycles per degree of visual angle, respectively). The Tukey Honestly Significant Difference post hoc test showed significant differences (p < .05) for all of the tested spatial frequencies. The largest difference between groups was in the lowest spatial frequency. Therefore, epilepsy may cause more damage to the neural pathways that process low spatial frequencies. However, epilepsy probably alters both the magnocellular visual pathway, which processes low spatial frequencies, and the parvocellular visual pathway, which processes high spatial frequencies. The experimental group had lower visual contrast sensitivity to all tested spatial frequencies

Comparative evolutionary patterns of Burkholderia cenocepacia and B. multivorans during chronic co-infection of a cystic fibrosis patient lung

During chronic respiratory infections of cystic fibrosis (CF) patients, bacteria adaptively evolve in response to the nutritional and immune environment as well as influence other infecting microbes. The present study was designed to gain insights into the genetic mechanisms underlying adaptation and diversification by the two most prevalent pathogenic species of the Burkholderia cepacia complex (Bcc), B. cenocepacia and B. multivorans. Herein, we study the evolution of both of these species during coinfection of a CF patient for 4.4 years using genome sequences of 9 B. multivorans and 11 B. cenocepacia. This co-infection spanned at least 3 years following initial infection by B. multivorans and ultimately ended in the patient’s death by cepacia syndrome. Both species acquired several mutations with accumulation rates of 2.08 (B. cenocepacia) and 2.27 (B. multivorans) SNPs/year. Many of the mutated genes are associated with oxidative stress response, transition metal metabolism, defense mechanisms against antibiotics, and other metabolic alterations consistent with the idea that positive selection might be driven by the action of the host immune system, antibiotic therapy and low oxygen and iron concentrations. Two orthologous genes shared by B. cenocepacia and B. multivorans were found to be under strong selection and accumulated mutations associated with lineage diversification. One gene encodes a nucleotide sugar dehydratase involved in lipopolysaccharide O-antigen (OAg) biosynthesis (wbiI). The other gene encodes a putative two-component regulatory sensor kinase protein required to sense and adapt to oxidative- and heavy metal- inducing stresses. This study contributes to understanding of shared and species-specific evolutionary patterns of B. cenocepacia and B. multivorans evolving in the same CF lung environment

The reality of acoustic power emitted by therapeutic ultrasound equipment: a revision

The safety and efficiency of ultrasonic therapy may be compromised if the outlet power on the tranducer differs considerably from the value indicated on the equipment panel. This fact may be seen in the various publications which approach the referenced theme, where various studies determine that over 50% of equipment in routine use in clinics and physiotherapy departments are out of the specifications recommended by the International Electrotechinical Commission (IEC). This occurs as a result of the non regulation of technical production standards, the wear of the equipment itself in use and by the non adoption of routine metrological procedures on the part of the physiotherapist. The precision of the acoustic intensity would enable a more efficient therapy, besides the reproduction of protocols already defined in literature. Another important factor to be pointed out is the material used for coupling the ultrasonic transducer, where of the various means utilized, some propiciate the atenuation of irradiated energy. This revision intends to update the professional therapeutic ultrasound user, as well as make him aware of the need for adopting metrological measures for the equipment in use as routine practice.A segurança e a eficiência da terapia ultra-sônica poderá ser comprometida se a potência de saída no transdutor diferir consideravelmente do valor indicado no painel do equipamento. Este fato pode ser evidenciado nas várias publicações que abordam o referido tema, onde diversos estudos determinam que mais de 50% dos equipamentos, em uso rotineiro, nas clínicas e departamentos de fisioterapia estão fora das especificações postuladas pela International Eletrotechinical Commission (IEC) . Isso ocorre em função da não regulamentação das normas técnicas de produção, do próprio desgaste do equipamento em uso e pela não adoção de procedimentos metrológicos de rotina por parte do fisioterapeuta. A precisão da intensidade acústica irá possibilitar uma terapia mais eficiente, além da reprodução de protocolos já definidos na literatura. Outro importante fator a ser destacado é o material utilizado para o acoplamento do transdutor ultra-sônico, onde evidencia-se que dos vários meios utilizados, alguns propiciam a atenuação da energia irradiada. Esta revisão pretende atualizar o profissional usuário do ultra-som terapêutico, bem como conscientizá-lo da necessidade de adoção de medidas metrológicas como prática de rotina para os equipamentos em uso

Protective Coatings Based on PMMA–Silica Nanocomposites Reinforced with Carbon Nanotubes

Polymethylmethacrylate–silica hybrids have been prepared using the sol–gel route by the radical polymerization of methyl methacrylate(MMA) using benzoyl peroxide (BPO) as a thermal initiator and 3-(trimethoxysilyl)propyl methacrylate(MPTS) as a coupling agent, followed by acid-catalyzed hydrolytic condensation of tetraethoxysilane (TEOS). Carbon nanotubes (CNTs) were first dispersed either by surfactant addition or by functionalization with carboxyl groups and then added at a carbon (CNT) to silicon (TEOS and MPTS) molar ratio (CCNT/SiHybrid) of 0.05% to two different hybrid matrices prepared at BPO/MMA molar ratios of 0.01 and 0.05. Films of 2–7 μm thickness deposited onto carbon steel by dip-coating were characterized in terms of their microstructure and their mechanical, thermal and anticorrosive behavior. Atomic force microscopy and optical microscopy confirmed that there was a homogeneous dispersion of CNTs in the nanocomposites and that the surfaces of the films were very smooth. X-ray photoelectron spectroscopy (XPS) confirmed the nominal composition of the films while nuclear magnetic resonance showed that the connectivity of the silica network was unaffected by CNT loading. Thermogravimetric analysis and mechanical measurements confirmed an increase of thermal stability, hardness, adhesion and scratch resistance of CNT-loaded coatings relative to those without CNTs. Electrochemical impedance spectroscopy measurements in 3.5% NaCl solution interpreted in terms of equivalent circuits showed that the reinforced hybrid coatings, prepared at the higher BPO/MMA molar ratio used in this work, act as a very efficient anticorrosive barrier, with an impedance modulus up to 109 Ω cm2

On the structure of high performance anticorrosive PMMA–siloxane–silica hybrid coatings

Environmentally compliant organic–inorganic hybrid coatings for efficient corrosion protection of metallic surfaces are potential alternatives to the current method based on chromate passivation. In this context PMMA–siloxane–silica (PMMA–SS) hybrid films were prepared using the sol–gel process from the radical copolymerization of methyl methacrylate and 3-(trimethoxysilyl)propyl methacrylate followed by acidic hydrolysis and polycondensation of tetraethoxysilane (TEOS), under variation of the ethanol to H2O ratio (0.0–1.0). The structural properties of about 2 μm thick coatings, deposited by dip-coating onto carbon steel, were related with their corrosion protection efficiency. The correlation of data obtained by X-ray photoelectron spectroscopy, nuclear magnetic resonance and small angle X-ray scattering has shown for intermediate ethanol to H2O ratios the highest connectivity (∼83%) of the inorganic phase, bonded covalently to organic moieties, yielding a dense and homogeneous nanocomposite structure with high thermal stability, very good adhesion to the metallic substrate and excellent barrier properties. The electrochemical impedance spectroscopy measurements have shown for coatings prepared at intermediate EtOH/H2O ratios a high corrosion resistance of almost 10 GΩ cm2, which remained unchanged for more than 6 months in contact with 3.5% NaCl solution and more than 3 months exposed to an acidic NaCl environment

Modulatory effects of cAMP and PKC activation on gap junctional intercellular communication among thymic epithelial cells

<p>Abstract</p> <p>Background</p> <p>We investigated the effects of the signaling molecules, cyclic AMP (cAMP) and protein-kinase C (PKC), on gap junctional intercellular communication (GJIC) between thymic epithelial cells (TEC).</p> <p>Results</p> <p>Treatment with 8-Br-cAMP, a cAMP analog; or forskolin, which stimulates cAMP production, resulted in an increase in dye transfer between adjacent TEC, inducing a three-fold enhancement in the mean fluorescence of coupled cells, ascertained by flow cytometry after calcein transfer. These treatments also increased Cx43 mRNA expression, and stimulated Cx43 protein accumulation in regions of intercellular contacts. VIP, adenosine, and epinephrine which may also signal through cyclic nucleotides were tested. The first two molecules did not mimic the effects of 8-Br-cAMP, however epinephrine was able to increase GJIC suggesting that this molecule functions as an endogenous inter-TEC GJIC modulators. Stimulation of PKC by phorbol-myristate-acetate inhibited inter-TEC GJIC. Importantly, both the enhancing and the decreasing effects, respectively induced by cAMP and PKC, were observed in both mouse and human TEC preparations. Lastly, experiments using mouse thymocyte/TEC heterocellular co-cultures suggested that the presence of thymocytes does not affect the degree of inter-TEC GJIC.</p> <p>Conclusions</p> <p>Overall, our data indicate that cAMP and PKC intracellular pathways are involved in the homeostatic control of the gap junction-mediated communication in the thymic epithelium, exerting respectively a positive and negative role upon cell coupling. This control is phylogenetically conserved in the thymus, since it was seen in both mouse and human TEC preparations. Lastly, our work provides new clues for a better understanding of how the thymic epithelial network can work as a physiological syncytium.</p

Attenuation of motor deficits by hydroethanolic extract of Poincianella pyramidalis in a Parkinson's disease model

The present study aimed to evaluate the possible neuroprotective effect of the hydroethanolic extract of Poincianella pyramidalis (EFIPp) (Tul.) L. P. Queiroz (Fabaceae), an endemic plant found in Northeastern Brazil, commonly used in folk medicine, on the motor deficits induced by repeated treatment with reserpine (RES) in rats. Adult male Wistar rats received 10 s.c. injections of 0.1 mg/kg RES or vehicle (VR), every 48 h, and daily i.p. injections daily of HEPp (25 mg/kg) or vehicle (VE). Throughout treatment, catalepsy behavior and oral movements were scored. After behavioral tests, superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in the prefrontal cortex, hippocampus and striatum. RES treatment induced a progressive increase of catalepsy time in the treated group compared to control groups starting at day 15. RES also increased the number of vacuous chewing movements, tongue protrusions and duration of facial twitching. Treatment with HEPp attenuated the motor deficit in the catalepsy test and delayed the onset of oral movements induced by RES. No significant changes were observed in the antioxidant assay. Taken together, these results show a beneficial effect of HEPp on motor deficits induced by reserpine, suggesting a neuroprotective effect in a rat model of PD.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Fundação de Apoio a Pesquisa e a Inovação Tecnologica do Estado de Sergipe (FAPITEC)Pro-reitoria de Pesquisa da Universidade Federal de Sergipe (POSGRAP/UFS)Univ Fed Sergipe, Dept Physiol, Sao Cristovao, SE, BrazilUniv Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USAMinist Educ, CAPES Fdn, BR-70040020 Brasilia, DF, BrazilUniv Fed Sao Paulo, Dept Biosci, Santos, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP, BrazilUniv Fed Sergipe, Dept Biosci, Itabaiana, SE, BrazilUniv Fed Sao Paulo, Dept Biosci, Santos, SP, BrazilUniv Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP, BrazilWeb of Scienc

MarinEye - A tool for marine monitoring

This work presents an autonomous system for marine integrated physical-chemical and biological monitoring – the MarinEye system. It comprises a set of sensors providing diverse and relevant information for oceanic environment characterization and marine biology studies. It is constituted by a physicalchemical water properties sensor suite, a water filtration and sampling system for DNA collection, a plankton imaging system and biomass assessment acoustic system. The MarinEye system has onboard computational and logging capabilities allowing it either for autonomous operation or for integration in other marine observing systems (such as Observatories or robotic vehicles. It was designed in order to collect integrated multi-trophic monitoring data. The validation in operational environment on 3 marine observatories: RAIA, BerlengasWatch and Cascais on the coast of Portugal is also discussed.info:eu-repo/semantics/publishedVersio