178 research outputs found

    Cellular eIF2B subunit localisation: implications for the integrated stress response and its control by small molecule drugs

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    eIF2 is a G protein critical for translation. It is tightly regulated in the integrated stress response (ISR) via phosphorylation of eIF2α and the subsequent control of eIF2B, a multisubunit guanine nucleotide exchange factor (GEF). Through studying the localisation of eIF2B subunits we identified cytoplasmic eIF2B bodies in mammalian cells. We highlight a relationship between body size and the eIF2B subunits localising to them; larger bodies contain all subunits and smaller bodies contain predominantly catalytic subunits. eIF2 localises to eIF2B bodies and shuttles within these bodies in a manner which correlates with eIF2B activity. Upon stress eIF2α-P localises predominately to larger bodies and results in a decreased shuttling of eIF2. Interestingly drugs which inhibit the ISR can rescue eIF2 shuttling in a manner correlating to levels of eIF2α-P. In contrast, smaller bodies show increased eIF2 shuttling in response to stress, which is accompanied by the localisation of eIF2Bδ to these bodies, suggesting the formation of a novel trimeric complex of eIF2B. This response is mimicked by ISR inhibiting drugs, providing insight into their potential mechanism of action. This study provides evidence that the composition and function of mammalian eIF2B bodies is regulated by the ISR and drugs which control it

    Predicting Incomplete Basal Cell Carcinoma Excisions - a Large Multidisciplinary Retrospective Analysis in a Tertiary Center

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    Introduction: Surgical treatment of basal cell carcinomas is often performed by physicians with different surgical backgrounds. Collecting data from different surgical departments would better reflect their real-life surgical management.Objectives: To identify the rate, recurrence risk, and predictive factors accordingly to their relative contribution for an incomplete basal cell carcinoma excision in a large multidisciplinary real-life settingMethods: Retrospective cohort study of 2305 surgically treated lesions in different departments of a tertiary center.Results: There was a rate of incomplete excisions (15%) and a recurrence rate (35.5% vs. 6.8% in incomplete vs. complete excisions (p < .001)). A third of incompletely excised basal cell carcinoma (BCC) will recur over time. Stratified by relevancy, high-risk histological subtypes (micronodular (OR 5.10 - p < .001) and morpheaform (OR 5.42 - p < .001), smaller specimen sizes ( <0.5 cm or 0.5-1 cm, OR 3.99 and 2.49, respectively, p < .001) high-risk locations (OR 3.06 on the nose, OR 2.77 on the eyelids, p < .001), and recurrent BCCs (OR 1.72, p < .001). are the best predictors of an incomplete excision.Conclusions: Acknowledging the rate, recurrence risk and predictive factors for incomplete excisions may be beneficial for optimal preoperative planning and to prevent unwarranted re-interventions, morbidity, and healthcare costs.info:eu-repo/semantics/publishedVersio

    Effect of the inherent variation in the mineral concentration of alfafa cultivars on aphid populations.

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    Plants have inherent variability of mineral content which affects their physiology and consequently the herbivorous insects feeding on them. Besides, insects need considerable amounts of potassium, phosphorus and magnesium in their diets, whereas little calcium, sodium and chloride are required. In this study, the inherent variation on mineral (Ca, S, Mg, N, P, K and also C:N ratio) concentrations and aphid (Acyrthosiphon spp., Therioaphis maculata, Aphis craccivora) populations on three alfalfa (Medicago sativa) cultivars (P3; Crioula, the most widely cultivated in Brazil, and CUF 101, an aphid-resistant) were studied between September/1997 and August/1998. A significant variation on mineral concentrations and aphid populations was observed among different sampling times and cultivars. The correlations between C:N ratio, Mg, N, P and S concentrations and aphid density variation suggest that the mineral status affects aphid population dynamics under field conditions

    The OPERA experiment Target Tracker

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    The main task of the Target Tracker detector of the long baseline neutrino oscillation OPERA experiment is to locate in which of the target elementary constituents, the lead/emulsion bricks, the neutrino interactions have occurred and also to give calorimetric information about each event. The technology used consists in walls of two planes of plastic scintillator strips, one per transverse direction. Wavelength shifting fibres collect the light signal emitted by the scintillator strips and guide it to both ends where it is read by multi-anode photomultiplier tubes. All the elements used in the construction of this detector and its main characteristics are described.Comment: 25 pages, submitted to Nuclear Instrument and Method

    Mutagenicactivity of glycoallkaloids from Solanum palinacanthum Dunal (Solanaceae) found in the brazilian cerrado

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    Solanaceous plants are widely distributed around the world and they are traditionally used as drugs for the treatment of cancer and herpes, and include familiar foods such as potato, tomato and eggplant and some berries popular in Brazil. As part of a program of research on pharmacologically active new molecules, the aim in this study was to assess the mutagenic effects of Solanum palinacanthum, known popularly as joá. The crude 95% ethanol extract and purified solamargine obtained from the fruits of S. palinacanthum Dunal were investigated by the Ames test, using the Salmonella typhimurium strains TA98, TA97a, TA100 and TA102 as test organisms, with and without metabolic activation. The concentrations tested ranged from 0.07 to 15.0 mg/plate for the crude ethanolic extract and from 1.25 to 5.0 mg/plate for the solamargine. The results showed a mutagenic effect of both the extract and the solamargine in the TA98 strain (without metabolic activation). The present study showed the potential mutagenicity and suggests confirming this effect in other models, before recommending their indiscriminate consumption by the population.Colegio de Farmacéuticos de la Provincia de Buenos Aire

    Vellozia flavicans Mart. ex Schult. hydroalcoholic extract inhibits the neuromuscular blockade induced by Bothrops jararacussu venom

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    FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOBackground: Snakebite is a significant public health issue in tropical countries. In Brazil, some of the most common snake envenomations are from Bothrops. Bothrops bites trigger local and systemic effects including edema, pain, erythema, cyanosis, infections, and necrosis. Vellozia flavicans is a plant from the Brazilian " cerrado" (savanna) that is popularly used as an anti-inflammatory medicine. Since inflammation develops quickly after Bothrops bites, which can lead to infection, the aim of the present study was to observe possible anti-snake venom and antimicrobial activities of V. flavicans (Vf). Methods: The chromatographic profile of the main constituents from the Vf leaf hydroalcoholic extract was obtained by thin-layer chromatography (TLC). The anti-snake venom activity was measured by Vf's ability to neutralize the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu) in a mouse phrenic nerve-diaphragm model (PND). After a 20 min incubation, preparations of PND were added to Tyrode's solution (control); Vf (0.2, 0.5, 1, and 2 mg/mL); 40 μg/mL Bjssu; pre-incubation for 30 min with Bjssu and 1 mg/mL Vf; and a Bjssu pretreated preparation (for 10 min) followed by 1 mg/mL Vf. Myographic recording was performed, and the contractile responses were recorded. The antimicrobial activity (minimum inhibitory concentration [MIC] and minimum bactericidal concentration [MBC]) was obtained for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, using gentamicin and vancomycin as positive controls. Results: TLC analysis yielded several compounds from Vf, such as flavonoids (quercetin) and phenolic acids (chlorogenic acid). Bjssu completely blocked the contractile responses of PND preparations, while Vf preserved 97% (±10%) of the contractile responses when incubated with Bjssu. In the PND pretreated with Bjssu, Vf was able to inhibit the neuromuscular blockade progress. MIC and MBC of Vf ranged from 2.5 to 5.0 mg/mL for P. aeruginosa and S. aureus strains, while no antimicrobial activity was observed for E. coli and E. faecalis.Conclusions: The hydroalcoholic extract from Vf leaves was able to neutralize and decrease the in vitro neuromuscular blockade caused by Bjssu. However, it did not show significant antimicrobial activity against the tested bacteria. © 2014 Tribuiani et al.; licensee BioMed Central Ltd.Snakebite is a significant public health issue in tropical countries. In Brazil, some of the most common snake envenomations are from Bothrops. Bothrops bites trigger local and systemic effects including edema, pain, erythema, cyanosis, infections, and necrosis. Vellozia flavicans is a plant from the Brazilian "cerrado" (savanna) that is popularly used as an anti-inflammatory medicine. Since inflammation develops quickly after Bothrops bites, which can lead to infection, the aim of the present study was to observe possible anti-snake venom and antimicrobial activities of V. flavicans (Vf). The chromatographic profile of the main constituents from the Vf leaf hydroalcoholic extract was obtained by thin-layer chromatography (TLC). The anti-snake venom activity was measured by Vf's ability to neutralize the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu) in a mouse phrenic nerve-diaphragm model (PND). After a 20 min incubation, preparations of PND were added to Tyrode's solution (control); Vf (0.2, 0.5, 1, and 2 mg/mL); 40 μg/mL Bjssu; pre-incubation for 30 min with Bjssu and 1 mg/mL Vf; and a Bjssu pretreated preparation (for 10 min) followed by 1 mg/mL Vf. Myographic recording was performed, and the contractile responses were recorded. The antimicrobial activity (minimum inhibitory concentration [MIC] and minimum bactericidal concentration [MBC]) was obtained for Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis, using gentamicin and vancomycin as positive controls. TLC analysis yielded several compounds from Vf, such as flavonoids (quercetin) and phenolic acids (chlorogenic acid). Bjssu completely blocked the contractile responses of PND preparations, while Vf preserved 97% (±10%) of the contractile responses when incubated with Bjssu. In the PND pretreated with Bjssu, Vf was able to inhibit the neuromuscular blockade progress. MIC and MBC of Vf ranged from 2.5 to 5.0 mg/mL for P. aeruginosa and S. aureus strains, while no antimicrobial activity was observed for E. coli and E. faecalis. The hydroalcoholic extract from Vf leaves was able to neutralize and decrease the in vitro neuromuscular blockade caused by Bjssu. However, it did not show significant antimicrobial activity against the tested bacteria14FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2004/09705-8; 2007/53883-6; 2008/52643-4; 2008/11005-5; 2012/08271-0Neglected tropical diseases: Snakebite, , http://www.who.int/bloodproducts/animal_sera/Rabies.pdf?ua=1, WHO - World Health Organization(2009) Textos Básicos de Saúde (Cadernos de Atenção Básican. 22), , Health surveillance:zoonoses, Brasil. 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(Flacourtiaceae) extracts (2008) Phytother Res, 22, pp. 784-790Camargo, T.M., Nazato, V.S., Silva, M.G., Cogo, J.C., Groppo, F.C., Oshima-Franco, Y., Bothrops jararacussu venom-induced neuromuscular blockade inhibited by Casearia gossypiosperma Briquet hydroalcoholic extract (2010) J Venom Anim Toxins incl Trop Dis, 16, pp. 432-441Nazato, V.S., Rubem Mauro, L., Vieira, N.A.G., Rocha Junior, D., Dos, S., Silva, M.G., Lopes, P.S., Oshima Franco, Y., vitro antiophidian properties of Dipteryx alata Vogel bark extracts (2010) Molecules, 15, pp. 5956-5970Melo, R.F., Farrapo, N.M., Rocha Junior, D.S., Silva, M.G., Cogo, J.C., Dal Belo, C.A., Rodrigues Simioni, L., Oshima Franco, Y., Antiophidian mechanisms of medicinal plants (2009) Flavonoids: Biosynthesis, Biological Effects and Dietary Sources, pp. 249-262. , New York: Nova Science Publishers, Keller RBFarrapo, N.M., Silva, G.A.A., Costa, K.N., Silva, M.G., Cogo, J.C., Dal Belo, C.A., Dos Santos, M.G., Oshima Franco, Y., Inhibition of Bothrops jararacussu venom activities by Plathymenia reticulata Benth extracts (2011) J Venom Res, 2, pp. 52-58Cos, P., Vlietinc, A.J., Berghe, D.V., Maes, L., Anti-infective potential of natural products: how to develop a stronger in vitro 'proof-of-concept' (2006) J Ethnopharmacol, 103, pp. 290-302Mishra, U.S., Mishra, A., Kumari, R., Murthy, P.N., Naik, B.S., Antibacterial activity of ethanol extract of Andrographis paniculata (2009) Indian J Pharm Sci, 71, pp. 436-438Premendran, S.J., Salwe, K.J., Pathak, S., Brahmane, R., Manimekalai, K., Anti-cobra venom activity of plant Andrographis paniculata and its comparison with polyvalent anti-snake venom (2011) J Nat Sci Biol Med, 2, pp. 198-204Mahadeswaraswamy, Y.H., Nagaraju, S., Girish, K.S., Kemparaju, K., Local tissue destruction and procoagulation properties of Echis carinatus venom: inhibition by Vitis vinifera seed methanol extract (2008) Phytother Res, 22, pp. 963-969Oliveira, D.A., Salvador, A.A., Smânia, A., Smânia, E.F., Maraschin, M., Ferreira, S.R., Antimicrobial activity and composition profile of grape (Vitis vinifera) pomace extracts obtained by supercritical fluids (2013) J Biotechnol, 164, pp. 423-43

    Monitoring Antibiotic Comsumption in the Surgery and Orthopaedics

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    A monitorização do consumo de antimicrobianos é um instrumento de interesse indiscutível e tem merecido uma atenção particular nos últimos anos, devido às crescentes preocupações com a emergência de estirpes microbianas multi-resistentes. Os objectivos do presente estudo consistiram, por um lado, na monitorização do consumo e na avaliação do impacto económico da prescrição hospitalar de antimicrobianos, em serviços de cirurgia e ortopedia. Por outro lado, pretendeu-se estudar e a relação indicação-prescrição terapêutica e profilática. Tendo presentes estes objectivos realizou-se um estudo-piloto longitudinal, com recolha de dados durante o mês de Maio de 2004, em seis Hospitais SA, incidindo numa amostra total de 1.122 doentes internados. Verificámos uma taxa de incidência de prescrição de 76,9%, com dispensa de 1.154 antimicrobianos, dos quais 71,2% se destinaram, em média, à profilaxia da infecção pós-cirúrgica, atestando a adesão geral à prática da profilaxia da infecção no local cirúrgico. O custo médio da antibioterapia foi mais elevado nos casos de “suspeita de infecção” (€9,09) ou “infecção declarada” (€8,74) e mais baixo quando utilizados para “profilaxia” (€5,67), facto relacionado com a menor duração média dos episódios de profilaxia. Os regimes de profilaxia utilizados apresentaram variações consideráveis entre os diferentes hospitais no que respeita ao tipo de antibiótico utilizado e uma duração média de 2,61 dias, com cerca de metade dos episódios de profilaxia prolongando-se por mais de 24 horas, sugerindo uma implementação insuficiente das actuais recomendações quanto ao tipo de fármaco a utilizar para esta prática, o que aponta para o necessidade duma avaliação da existência nas unidades hospitalares, de recomendações claras para a profilaxia da infecção do local cirúrgico, bem como da adesão dos clínicos a estas

    Hadron Energy Reconstruction for the ATLAS Calorimetry in the Framework of the Non-parametrical Method

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    This paper discusses hadron energy reconstruction for the ATLAS barrel prototype combined calorimeter (consisting of a lead-liquid argon electromagnetic part and an iron-scintillator hadronic part) in the framework of the non-parametrical method. The non-parametrical method utilizes only the known e/he/h ratios and the electron calibration constants and does not require the determination of any parameters by a minimization technique. Thus, this technique lends itself to an easy use in a first level trigger. The reconstructed mean values of the hadron energies are within ±1\pm 1% of the true values and the fractional energy resolution is [(58±3)/E+(2.5±0.3)[(58\pm3)% /\sqrt{E}+(2.5\pm0.3)%]\oplus (1.7\pm0.2)/E. The value of the e/he/h ratio obtained for the electromagnetic compartment of the combined calorimeter is 1.74±0.041.74\pm0.04 and agrees with the prediction that e/h>1.7e/h > 1.7 for this electromagnetic calorimeter. Results of a study of the longitudinal hadronic shower development are also presented. The data have been taken in the H8 beam line of the CERN SPS using pions of energies from 10 to 300 GeV.Comment: 33 pages, 13 figures, Will be published in NIM

    Analysing interactions in a teacher network forum: a sociometric approach

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    This article presents the sociometric analysis of the interactions in a forum of a social network created for the professional development of Portuguese-speaking teachers. The main goal of the forum, which was titled Stricto Sensu, was to discuss the educational value of programmes that joined the distance learning model in Brazil. The empirical study focused on the sociometrie analysis of the social interactions that take place in asynchronous online environments. This approach, according to literature, allows for new means to observe, analyse, and interpret the reality of a new social paradigm. This type of analysis tries to understand the relationship established between the different actors, seeking to verify if the roles they play in both the access to information and the construction of shared knowledge. The data collected allow the researchers to deduce that the indicators used in the analysis are important for understanding and intervening in the dynamics and functioning of the network to propose improvements in its structure and organisation. In the specific case of the aforementioned discussion forum, the results of the sociometrie analysis of the perceived interactions were not surprising, considering that the nature of the topic did not demand deep reflection to contribute to the debate.This work is funded by Portuguese Foundation for Science and Technology under the doctoral grant SFRH/BD/60677/2009

    Gluon polarization in the nucleon from quasi-real photoproduction of high-pT hadron pairs

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    We present a determination of the gluon polarization Delta G/G in the nucleon, based on the helicity asymmetry of quasi-real photoproduction events, Q^2<1(GeV/c)^2, with a pair of large transverse-momentum hadrons in the final state. The data were obtained by the COMPASS experiment at CERN using a 160 GeV polarized muon beam scattered on a polarized 6-LiD target. The helicity asymmetry for the selected events is = 0.002 +- 0.019(stat.) +- 0.003(syst.). From this value, we obtain in a leading-order QCD analysis Delta G/G=0.024 +- 0.089(stat.) +- 0.057(syst.) at x_g = 0.095 and mu^2 =~ 3 (GeV}/c)^2.Comment: 10 pages, 3 figure
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