Descriptor-and fragment-based QSAR models for a series of Schistosoma mansoni purine nucleoside inhibitors

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the treatment of major parasitic infectious diseases, with special emphasis on its role in the discovery of new drugs against schistosomiasis, a tropical disease that affects millions of people worldwide. In the present work, we have determined the inhibitory potency and developed descriptor- and fragment-based quantitative structure-activity relationships (QSAR) for a series of 9-deazaguanine analogs as inhibitors of SmPNP. Significant statistical parameters (descriptor-based model: r² = 0.79, q² = 0.62, r²pred = 0.52; and fragment-based model: r² = 0.95, q² = 0.81, r²pred = 0.80) were obtained, indicating the potential of the models for untested compounds. The fragment-based model was then used to predict the inhibitory potency of a test set of compounds, and the predicted values are in good agreement with the experimental results

Neural networks and statistical analysis for classification of corneal videokeratography maps based on Zernike coefficients: a quantitative comparison

PURPOSE: The main goal of this study was to develop and compare two different techniques for classification of specific types of corneal shapes when Zernike coefficients are used as inputs. A feed-forward artificial Neural Network (NN) and discriminant analysis (DA) techniques were used. METHODS: The inputs both for the NN and DA were the first 15 standard Zernike coefficients for 80 previously classified corneal elevation data files from an Eyesys System 2000 Videokeratograph (VK), installed at the Departamento de Oftalmologia of the Escola Paulista de Medicina, São Paulo. The NN had 5 output neurons which were associated with 5 typical corneal shapes: keratoconus, with-the-rule astigmatism, against-the-rule astigmatism, "regular" or "normal" shape and post-PRK. RESULTS: The NN and DA responses were statistically analyzed in terms of precision ([true positive+true negative]/total number of cases). Mean overall results for all cases for the NN and DA techniques were, respectively, 94% and 84.8%. CONCLUSION: Although we used a relatively small database, results obtained in the present study indicate that Zernike polynomials as descriptors of corneal shape may be a reliable parameter as input data for diagnostic automation of VK maps, using either NN or DA.

Métodos utilizados na avaliação psicofísica da visão de cores humana

A cor é um atributo perceptual que nos permite identificar e localizar padrões ambientais de mesmo brilho e constitui uma dimensão adicional na identificação de objetos, além da detecção de inúmeros outros atributos dos objetos em sua relação com a cena visual, como luminância, contraste, forma, movimento, textura, profundidade. Decorre daí a sua importância fundamental nas atividades desempenhadas pelos animais e pelos seres humanos em sua interação com o ambiente. A psicofísica visual preocupa-se com o estudo quantitativo da relação entre eventos físicos de estimulação sensorial e a resposta comportamental resultante desta estimulação, fornecendo dessa maneira meios de avaliar aspectos da visão humana, como a visão de cores. Este artigo tem o objetivo de mostrar diversas técnicas eficientes na avaliação da visão cromática humana através de métodos psicofísicos adaptativos.

Comparação entre o método clássico de Gibson e Cooke e o teste da condutividade no suor em pacientes com e sem fibrose cística

OBJETIVO: Comparar os valores de cloro no suor obtidos pelo teste quantitativo da iontoforese pela pilocarpina (teste clássico) com os valores de condutividade no suor obtidos pelo sistema de coleta por Macroduct® em pacientes com e sem fibrose cística (FC). O custo e tempo despendidos na execução de cada teste foram também analisados. MÉTODOS: O teste do suor pelas duas técnicas foi realizado simultaneamente, em pacientes com e sem FC. Os pontos de corte para a condutividade para excluir ou diagnosticar FC foram < 75 e > 90 mmol/L, respectivamente, e, para o teste clássico, cloro < 60 e > 60 mmol/L. RESULTADOS: Cinquenta e dois pacientes com FC (29 do sexo masculino e 23 do sexo feminino; de 1,5 a 18,2 anos) realizaram o teste do suor pelas duas técnicas, apresentando valores medianos de cloro e condutividade no suor de 114 e 122 mmol/L, respectivamente. Em todos eles, a condutividade foi > 95 mmol/L, o que conferiu ao teste 100% de sensibilidade (IC95% 93,1-100). Cinquenta pacientes sem FC (24 do sexo masculino e 26 do sexo feminino; de 0,5 a 12,5 anos) apresentaram valores medianos de cloro e condutividade no suor de 15,5 e 30 mmol/L, respectivamente. Em todos os casos, a condutividade foi < 70 mmol/L, o que conferiu ao teste 100% de especificidade (IC95% 92,9-100). O tempo despendido na execução dos testes foi significativamente menor com o teste da condutividade, e o seu custo também foi inferior. CONCLUSÕES: O teste da condutividade apresentou alta sensibilidade e especificidade, e houve boa correspondência entre os testes. O tempo de execução foi mais rápido e o custo inferior na aplicação do teste da condutividade em relação ao teste clássico.

Pathogenicity of different rabies virus isolates and protection test in vaccinated mice

This study was aimed to evaluate and compare the pathogenicity of rabies virus isolated from bats and dogs, and to verify the efficacy of a commercial rabies vaccine against these isolates. For evaluation of pathogenicity, mice were inoculated by the intramuscular route (IM) with 500MICLD50/0.03mL of the viruses. The cross-protection test was performed by vaccinating groups of mice by the subcutaneous route and challenged through the intracerebral (IC) route. Isolates were fully pathogenic when inoculated by the IC route. When inoculated intramuscularly, the pathogenicity observed showed different death rates: 60.0% for the Desmodus rotundus isolate; 50.0% for dog and Nyctinomops laticaudatus isolates; 40.0% for Artibeus lituratus isolate; 9.5% Molossus molossus isolate; and 5.2% for the Eptesicus furinalis isolate. Mice receiving two doses of the vaccine and challenged by the IC route with the isolates were fully protected. Mice receiving only one dose of vaccine were partially protected against the dog isolate. The isolates from bats were pathogenic by the IC route in mice. However, when inoculated through the intramuscular route, the same isolates were found with different degrees of pathogenicity. The results of this work suggest that a commercial vaccine protects mice from infection with bat rabies virus isolates, in addition to a canine rabies virus isolate.

The ability of the BANA test to detect different levels of P. gingivalis, T. denticola and T. forsythia

The aim of this study was to evaluate the ability of the BANA Test to detect different levels of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia or their combinations in subgingival samples at the initial diagnosis and after periodontal therapy. Periodontal sites with probing depths between 5-7 mm and clinical attachment level between 5-10 mm, from 53 subjects with chronic periodontitis, were sampled in four periods: initial diagnosis (T0), immediately (T1), 45 (T2) and 60 days (T3) after scaling and root planing. BANA Test and Checkerboard DNA-DNA hybridization identified red complex species in the subgingival biofilm. In all experimental periods, the highest frequencies of score 2 (Checkerboard DNA-DNA hybridization) for P. gingivalis, T. denticola and T. forsythia were observed when strong enzymatic activity (BANA) was present (p < 0.01). The best agreement was observed at initial diagnosis. The BANA Test sensitivity was 95.54% (T0), 65.18% (T1), 65.22% (T2) and 50.26% (T3). The specificity values were 12.24% (T0), 57.38% (T1), 46.27% (T2) and 53.48% (T3). The BANA Test is more effective for the detection of red complex pathogens when the bacterial levels are high, i.e. in the initial diagnosis of chronic periodontitis.

Effect of fructans-based fat replacer on chemical composition, starch digestibility and sensory acceptability of corn snacks

To develop a convenience healthy food snack the partially hydrogenated vegetable fat, used as the flavour fixative agent, was replaced by a non-fat-flavouring solution enriched with inulin and oligofructose. The effects of this replacement on chemical composition, in vitro rate of starch digestion and sensory acceptability were assessed. The new snack presented low-fat levels (0.1 per cent) and around a sevenfold increase in dietary fibre (15.3 per cent of dietary fibre, being 13.3 per cent of fructans) when compared with the traditional ones. The enrichment with fructans reduced the predicted Glycaemic Index by 25 per cent, thus indicating that this dietary fibre contributes effectively towards delaying the in vitro glycaemic response. Fructans-enriched snack presented overall acceptability score (6.6 ± 1.7) similar to the traditional one, flavoured with fatty fixative agent (7.4 ± 1.4). The healthy low-fat fibre-enriched snack produced presented the high sensory acceptability typical for this food product type

Effect of glutamate and inosinate on sensory and instrumental texture of extruded products

Expanded products have been developed by extrusion of non-conventional highly nutritious raw materials such as amaranth and chickpea blended with bovine lung. As sensory acceptance of these snacks is restricted, this study aimed at improving their texture, through the addition of monosodium glutamate (MSG) and disodium inosinate (IMP) flavor enhancers to the feeding material, or to the flavor added after the extrusion. Sensory and mechanical analyses showed that both enhancers affected texture, assessed by sensory and instrumental methods. Addition of IMP together with MSG to the chickpea-based snacks presented the best results. This beneficial effect was not observed in the amaranth-based snack, suggesting that IMP and MSG can favorably impact texture of extruded products depending on the amount and type of protein present

O Ginecologista obstetra e a internet

OBJETIVOS: identificar a influência do uso da internet na prática e ambiente de trabalho médico e verificar como estas mudanças vêm acorrendo entre médicos ginecologistas e obstetras. MÉTODO: foram enviados 1.120 questionários para médicos ginecologistas e obstetras da cidade de São Paulo, dos quais retornaram 152, o correspondente a 13,6 por cento da amostra ou 6,1 por cento do total dos médicos cadastrados na SOGESP. A análise quantitativa do comportamento do médico quanto ao uso da internet foi realizada por meio de proporções, médias, cálculos de desvios-padrão e do teste de associação de qui-quadrado. Através da técnica de Cluster Analysis, foram determinados 4 grupos segundo o perfil dos profissionais relacionado ao uso desta ferramenta. RESULTADOS: não se observou relação de idade, sexo, locais de trabalho e desenvolvimento de apenas uma das especialidades Ginecologia ou Obstetrícia quanto à utilização da internet na prática médica. Observou-se uma tendência de uso mais freqüente entre médicos com doutorado. Quanto aos serviços médicos prestados por e-mail, receber e devolver exames foram as atividades mais realizadas pelos sujeitos da pesquisa. CONCLUSÃO: os ginecologistas obstetras pesquisados utilizam a internet na prática médica para própria atualização, para comunicação com pacientes ou para oferecer serviços às mesmas com diferentes assiduidades. Entretanto, este uso é ainda parcial, talvez relacionado ao receio de interferências negativas na relação com o paciente, além de preocupações quanto à implicações legais, éticas e principalmente econômicas relacionadas à prática profissional

The full Bayesian significance test for mixture models: results in gene expression clustering

Gene clustering is a useful exploratory technique to group together genes with similar expression levels under distinct cell cycle phases or distinct conditions. It helps the biologist to identify potentially meaningful relationships between genes. In this study, we propose a clustering method based on multivariate normal mixture models, where the number of clusters is predicted via sequential hypothesis tests: at each step, the method considers a mixture model of m components (m = 2 in the first step) and tests if in fact it should be m - 1. If the hypothesis is rejected, m is increased and a new test is carried out. The method continues (increasing m) until the hypothesis is accepted. The theoretical core of the method is the full Bayesian significance test, an intuitive Bayesian approach, which needs no model complexity penalization nor positive probabilities for sharp hypotheses. Numerical experiments were based on a cDNA microarray dataset consisting of expression levels of 205 genes belonging to four functional categories, for 10 distinct strains of Saccharomyces cerevisiae. To analyze the method's sensitivity to data dimension, we performed principal components analysis on the original dataset and predicted the number of classes using 2 to 10 principal components. Compared to Mclust (model-based clustering), our method shows more consistent results.

Energy system contributions to the special judo fitness test

Purpose: This study investigated the energy system contributions of judo athletes to the Special Judo Fitness Test (SJFT). Methods: Fourteen male judo athletes performed the SJFT, which comprised three periods of judo activity (A = 15 s, B and C = 30 s) interspersed with 10 s rest intervals. During this test, one athlete threw two others positioned 6 m from each other using the ippon-seoi-nage technique. The fractions of the aerobic, anaerobic alactic and anaerobic lactic systems were calculated based on oxygen uptake, the fast component of excess postexercise oxygen uptake, and changes in net blood lactate, respectively. The contribution of the three energy systems was compared using a repeated measures analysis of variance and Bonferroni's multiple comparisons test. Compound symmetry, or sphericity, was determined by Mauchly's test. A level of significance of 5% (P < .05) was adopted in all analyses. Results: The alactic energy system presented a higher (F = 20.9; P < .001; power observed = 1.0) contribution (86.8 +/- 23.6 kJ; 42.3 +/- 5.9%) during the test when compared with both aerobic (57.1 +/- 11.3 kJ; 28.2 +/- 2.9%) and lactic (58.9 +/- 12.1 kJ; 29.5 +/- 6.2%) energy systems (P < .001 for both comparisons). Conclusions: The higher alactic contribution seems to be a consequence of the high-intensity efforts performed during the test, and its intermittent nature. Thus, when using the SJFT, coaches are evaluating mainly their athletes' anaerobic alactic system, which can be considered to be the most predominant system contributing to the actions (techniques) performed in the match.

Ventilation behavior in trained and untrained men during incremental test: evidence of one metabolic transition point

This study aimed to describe and compare the ventilation behavior during an incremental test utilizing three mathematical models and to compare the feature of ventilation curve fitted by the best mathematical model between aerobically trained (TR) and untrained ( UT) men. Thirty five subjects underwent a treadmill test with 1 km.h(-1) increases every minute until exhaustion. Ventilation averages of 20 seconds were plotted against time and fitted by: bi-segmental regression model (2SRM); three-segmental regression model (3SRM); and growth exponential model (GEM). Residual sum of squares (RSS) and mean square error (MSE) were calculated for each model. The correlations between peak VO2 (VO2PEAK), peak speed (Speed(PEAK)), ventilatory threshold identified by the best model (VT2SRM) and the first derivative calculated for workloads below (moderate intensity) and above (heavy intensity) VT2SRM were calculated. The RSS and MSE for GEM were significantly higher (p < 0.01) than for 2SRM and 3SRM in pooled data and in UT, but no significant difference was observed among the mathematical models in TR. In the pooled data, the first derivative of moderate intensities showed significant negative correlations with VT2SRM (r = -0.58; p < 0.01) and Speed(PEAK) (r = -0.46; p < 0.05) while the first derivative of heavy intensities showed significant negative correlation with VT2SRM (r = -0.43; p < 0.05). In UT group the first derivative of moderate intensities showed significant negative correlations with VT2SRM (r = -0.65; p < 0.05) and Speed(PEAK) (r = -0.61; p < 0.05), while the first derivative of heavy intensities showed significant negative correlation with VT2SRM (r= -0.73; p < 0.01), Speed(PEAK) (r = -0.73; p < 0.01) and VO2PEAK (r = -0.61; p < 0.05) in TR group. The ventilation behavior during incremental treadmill test tends to show only one threshold. UT subjects showed a slower ventilation increase during moderate intensities while TR subjects showed a slower ventilation increase during heavy intensities.

Genome wide scan for quantitative trait loci affecting tick resistance in cattle (Bos taurus x Bos indicus)

Background : In tropical countries, losses caused by bovine tick Rhipicephalus (Boophilus) microplus infestation have a tremendous economic impact on cattle production systems. Genetic variation between Bos taurus and Bos indicus to tick resistance and molecular biology tools might allow for the identification of molecular markers linked to resistance traits that could be used as an auxiliary tool in selection programs. The objective of this work was to identify QTL associated with tick resistance/susceptibility in a bovine F2 population derived from the Gyr (Bos indicus) x Holstein (Bos taurus) cross. Results: Through a whole genome scan with microsatellite markers, we were able to map six genomic regions associated with bovine tick resistance. For most QTL, we have found that depending on the tick evaluation season (dry and rainy) different sets of genes could be involved in the resistance mechanism. We identified dry season specific QTL on BTA 2 and 10, rainy season specific QTL on BTA 5, 11 and 27. We also found a highly significant genome wide QTL for both dry and rainy seasons in the central region of BTA 23. Conclusions: The experimental F2 population derived from Gyr x Holstein cross successfully allowed the identification of six highly significant QTL associated with tick resistance in cattle. QTL located on BTA 23 might be related with the bovine histocompatibility complex. Further investigation of these QTL will help to isolate candidate genes involved with tick resistance in cattle.

Validation of reference genes for gene expression studies in the honey bee, Apis mellifera, by quantitative real-time RT-PCR

For obtaining accurate and reliable gene expression results it is essential that quantitative real-time RT-PCR (qRT-PCR) data are normalized with appropriate reference genes. The current exponential increase in postgenomic studies on the honey bee, Apis mellifera, makes the standardization of qRT-PCR results an important task for ongoing community efforts. For this aim we selected four candidate reference genes (actin, ribosomal protein 49, elongation factor 1-alpha, tbp-association factor) and used three software-based approaches (geNorm, BestKeeper and NormFinder) to evaluate the suitability of these genes as endogenous controls. Their expression was examined during honey bee development, in different tissues, and after juvenile hormone exposure. Furthermore, the importance of choosing an appropriate reference gene was investigated for two developmentally regulated target genes. The results led us to consider all four candidate genes as suitable genes for normalization in A. mellifera. However, each condition evaluated in this study revealed a specific set of genes as the most appropriated ones.