A machine learning approach for genome-wide prediction of morbid and druggable human genes based on systems-level data

Background: The genome-wide identification of both morbid genes, i.e., those genes whose mutations cause hereditary human diseases, and druggable genes, i.e., genes coding for proteins whose modulation by small molecules elicits phenotypic effects, requires experimental approaches that are time-consuming and laborious. Thus, a computational approach which could accurately predict such genes on a genome-wide scale would be invaluable for accelerating the pace of discovery of causal relationships between genes and diseases as well as the determination of druggability of gene products.Results: In this paper we propose a machine learning-based computational approach to predict morbid and druggable genes on a genome-wide scale. For this purpose, we constructed a decision tree-based meta-classifier and trained it on datasets containing, for each morbid and druggable gene, network topological features, tissue expression profile and subcellular localization data as learning attributes. This meta-classifier correctly recovered 65% of known morbid genes with a precision of 66% and correctly recovered 78% of known druggable genes with a precision of 75%. It was than used to assign morbidity and druggability scores to genes not known to be morbid and druggable and we showed a good match between these scores and literature data. Finally, we generated decision trees by training the J48 algorithm on the morbidity and druggability datasets to discover cellular rules for morbidity and druggability and, among the rules, we found that the number of regulating transcription factors and plasma membrane localization are the most important factors to morbidity and druggability, respectively.Conclusions: We were able to demonstrate that network topological features along with tissue expression profile and subcellular localization can reliably predict human morbid and druggable genes on a genome-wide scale. Moreover, by constructing decision trees based on these data, we could discover cellular rules governing morbidity and druggability.

Prevalence of dog intestinal parasites and risk perception of zoonotic infection by dog owners in São Paulo State, Brazil

Coprological examination was used to estimate the prevalence of gastrointestinal parasites in stray and domiciled dogs from Botucatu, São Paulo State, Brazil. Risk factors for dog infection were assessed in relation to demographic, husbandry and management data. The dog owners completed a questionnaire survey on some aspects of dog parasitism such as parasite species, mechanisms of infection, awareness of zoonotic diseases and history of anthelmintic usage. Parasites were found in the faeces of 138 dogs, with an overall prevalence of 54.3%. Dogs harbouring one parasite were more common (31.4%) than those harbouring two (18.5%), three (3.2%) or four (1.2%). The following parasites and their respective frequencies were detected: Ancylostoma (37.8%), Giardia (16.9%), Toxocara canis (8.7%), Trichuris vulpis (7.1%), Dipylidium caninum (2.4%), Isospora (3.5%), Cryptosporidium (3.1%) and Sarcocystis (2.7%). Stray dogs were found more likely to be poliparasitized (P < 0.01) and presented higher prevalence of Ancylostoma, T. canis and Giardia (P < 0.01) than domiciled ones. Toxocara canis was detected more frequently in dogs with < 6 months of age (P < 0.05) and no effect of sex or breed could be observed (P > 0.05). Except for Ancylostoma, that showed a significantly higher prevalence in dogs living in a multi-dog household (P < 0.01), parasite prevalences were similar in single- and multi-dog household. The answers of dog owners to the questionnaire showed that the majority does not know the species of dog intestinal parasites, the mechanisms of transmission, the risk factors for zoonotic infections, and specific prophylactic measures. The predominance of zoonotic species in dogs in the studied region, associated with the elevated degree of misinformation of the owners, indicates that the risk of zoonotic infection by canine intestinal parasite may be high, even in one of the most developed regions of Brazil.

Androgen receptor in the Mongolian gerbil ventral prostate: Evaluation during different phases of postnatal development and following androgen blockage

The normal growth, differentiation and maintenance of the morphofunctional integrity of the prostate gland are dependent on the interaction of constant levels of androgens with their receptors. The need to study the responses to hormones under several conditions and the effect of their blockage is due to the fact that the human prostate is the site of a great number of age-related diseases, and the ones with a major medical importance are prostate cancer (Cap) and benign prostatic hyperplasia (BPH), which can both be treated with androgen suppression. Seventy-five male gerbils were divided, randomly, into 3 groups of 25 animals each, where each group corresponded to one phase of postnatal development. In each phase, it was possible to morphologically and stereologically analyze the compartments of prostatic ventral lobe, as well as to immunohistochemically analyze the degree of expression of androgen receptors (ARs) after the androgen blockage therapies. In addition, it was possible to establish the hormonal dosage of serum testosterone levels given the comparative approach of the expression of androgen receptors. There is a pattern of AR distribution in the prostatic ventral lobe throughout postnatal development, in which the younger the animal is the higher, the interaction of circulating androgens that stimulate the AR expression in both the epithelial and stromal compartments. The androgen blockage therapies decreased AR expression in the prostatic compartments, but the androgen reposition after these blockages was not sufficient to recover the glandular structure or stimulate the AR expression up to normal physiological conditions. Both the regulation and distribution of androgen receptors along the gerbil prostatic tissues are complex mechanisms that are likely to be genetically regulated by androgens prenatally or by other factors that are still unknown. This rodent species seems to be a valuable model in the attempt to improve the understanding of the morphophysiological and pathological behavior of this important gland in humans throughout aging and to stimulate new therapeutic ideas to fight prostate cancer. (C) 2008 Elsevier Ltd. All rights reserved.

Ligninases production by Basidiomycetes strains on lignocellulosic agricultural residues and their application in the decolorization of synthetic dyes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Salacia campestris root bark extract: peroxidase inhibition, antioxidant and antiradical profile

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Validated HPLC method for the standardization of Phyllanthus niruri (herb and commercial extracts) using corilagin as a phytochemical marker

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Genetic of the ABO blood system and its link with the immune system

Peter J. D'Adamo, autor do livro Eat Right For Your Type, escreve que o grupo O representa o primeiro tipo sangüíneo que surgiu nos humanos e também afirma que os grupos sangüíneos constituem as bases do sistema imune. Recentes estudos filogenéticos realizados em primatas humanos e não humanos estabeleceram que o gene A representa a forma ancestral dos genes que ocupam o locus ABO. Associações entre os grupos sangüíneos ABO, doenças infecciosas, não infecciosas e imunodeficiências também foram relatadas. Diante das proposições do autor, as quais se opõem às informações resultantes de recentes estudos moleculares e filogenéticos, nossa intenção é apresentar algumas reflexões sobre a genética e a evolução dos genes do sistema ABO e as conexões deste sistema com o sistema imune.

Screening of melon populations for resistance to Didymella bryoniae in greenhouse and plastic tunnel conditions

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Kinetic parameters of silicon uptake by rice cultivars

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efficacy and safety of a soy isoflavone extract in postmenopausal women: A randomized, double-blind, and placebo-controlled study

Objective: To investigate the efficacy of soy isoflavone on climacteric symptoms in postmenopausal women.Design: In this double-blind, randomized, placebo-controlled study, a total of 80 women (mean age =55.1 years), who reported 5 or more hot flush episodes per day, were randomized to receive either 250 mg of standardized soy extract (Glycine max AT) a total of 100 mg/day of isoflavone (n=40) or placebo (n=40). Exclusion criteria included: contra-indication for hormone therapy (HT), chronic gastrointestinal diseases, and users of HT within the preceding 6-months. For 10-months, climacteric symptoms were evaluated using a score card and the menopausal Kupperman index. Compliance and safety were also assessed. At baseline and the end of the study, lipid and hormonal profiles, as well as vaginal, mammographic and ultrasonographic parameters were measured. The t-test, Wilcoxon test and ANOVA were used in the statistical analysis.Results: At baseline, the mean number of hot flushes was 9.6 +/- 3.9 per day in the isoflavone group and 10.1 +/- 4.9 in the placebo group (p>0.05). After 10 months, there was a significant reduction in frequency of hot flushes among isoflavone users when compared to those on placebo (3.1 +/- 2.3 and 5.9 +/- 4.3, respectively) (p<0.001). Kupperman index mean values showed a significant reduction in both groups. However, soy isoflavone was significantly superior to placebo, in reducing hot flush severity (69.9% and 33.7%, respectively) (p<0.001). Endometrial thickness, mammography, vaginal cytology, lipids and hormonal profile did not change in both groups. No serious adverse event related to isoflavone treatment was reported.Conclusions: the soy isoflavone extract exerted favorable effects on vasomotor symptoms and good compliance, providing a safe and effective alternative therapeutic for postmenopausal women. (C) 2007 Elsevier B.V.. All rights reserved.

Effect of modifiers on thermal behaviour of Se in acid digestates and slurries of vegetables by graphite furnace atomic absorption spectrometry

The influence of sample preparation strategy of vegetables on the electrothermal behaviour of Se without and with chemical modifiers such as Pd(NO3)(2), Pd(NO3)(2) + Mg(NO3)(2), Pd(NO3)(2) + Cd(NO3)(2), pre-reduced Pd, Mg(NO3)(2), and Ni(NO3)(2) was investigated. Acid digestates and slurries of vegetables (0.1% m/v in 1% m/v HNO3 + 0.005% v/v of Triton X-100) were used to prepare reference solutions or slurries. For 10 mul of each modifier tested, pyrolysis and atomization temperatures were evaluated using pyrolysis and atomization curves, respectively. Best conditions, such as thermal stability, signal profile, repeatability and sensitivity were attained using Pd(NO3)(2) as chemical modifier. The following heating program (temperature, ramp/hold time) of the graphite tube of the Varian SpectrAA-800Z atomic absorption spectrometer was used: dry step (85 degreesC, 5/0 s; 95 degreesC, 40/0 s; 120 degreesC, 10/.5 s); pyrolysis step (1400 degreesC, 10/3s); atomization step (2200 degreesC, 1/2 s); clean step (2600 degreesC, 2/0 s). This pyrolysis temperature is 800 degreesC higher than when measuring without any modifier. For 20 muL sample volume and 10 mug Pd(NO3)(2), analytical curves in the 3.0-30 mug Se 1(-1) range were obtained. The method was applied for Se determination in acid digestates and slurries of 10 vegetable samples and one standard reference material (rice flower) and results were in agreement at 95% confidence level. Recoveries varied from 89 to 95% for spiked samples. The lifetime of the graphite tube was ca. 250 firings and the relative standard deviations (n = 12) for a typical acid digestate and slurry containing 20 mug Se 1(-1) were 3.8% and 8.3%, respectively. The limits of detection were 2.0 mug Se 1(-1) and 0.6 mug Se 1(-1) Se for digestates and slurries, respectively. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Hormonal therapy in the senescence: Prostatic microenvironment structure and adhesion molecules

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Experimental Basis and New Insights for Cell Therapy in Chronic Obstructive Pulmonary Disease

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cryopreservation at-80A degrees C of Agaricus blazei on rice grains

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)