An analysis of the positional distribution of DNA motifs in promoter regions and its biological relevance

BACKGROUND: Motif finding algorithms have developed in their ability to use computationally efficient methods to detect patterns in biological sequences. However the posterior classification of the output still suffers from some limitations, which makes it difficult to assess the biological significance of the motifs found. Previous work has highlighted the existence of positional bias of motifs in the DNA sequences, which might indicate not only that the pattern is important, but also provide hints of the positions where these patterns occur preferentially.RESULTS: We propose to integrate position uniformity tests and over-representation tests to improve the accuracy of the classification of motifs. Using artificial data, we have compared three different statistical tests (Chi-Square, Kolmogorov-Smirnov and a Chi-Square bootstrap) to assess whether a given motif occurs uniformly in the promoter region of a gene. Using the test that performed better in this dataset, we proceeded to study the positional distribution of several well known cis-regulatory elements, in the promoter sequences of different organisms (S. cerevisiae, H. sapiens, D. melanogaster, E. coli and several Dicotyledons plants). The results show that position conservation is relevant for the transcriptional machinery.CONCLUSION: We conclude that many biologically relevant motifs appear heterogeneously distributed in the promoter region of genes, and therefore, that non-uniformity is a good indicator of biological relevance and can be used to complement over-representation tests commonly used. In this article we present the results obtained for the S. cerevisiae data sets.publishersversionpublishe

The compound Poisson limit ruling periodic extreme behaviour of non-uniformly hyperbolic dynamics

We prove that the distributional limit of the normalised number of returns to small neighbourhoods of periodic points of non-uniformly hyperbolic dynamical systems is compound Poisson. The returns to small balls around a fixed point in the phase space correspond to the occurrence of rare events, or exceedances of high thresholds, so that there is a connection between the laws of Return Times Statistics and Extreme Value Laws. The fact that the fixed point in the phase space is a repelling periodic point implies that there is a tendency for the exceedances to appear in clusters whose average sizes is given by the Extremal Index, which depends on the expansion of the system at the periodic point. We recall that for generic points, the exceedances, in the limit, are singular and occur at Poisson times. However, around periodic points, the picture is different: the respective point processes of exceedances converge to a compound Poisson process, so instead of single exceedances, we have entire clusters of exceedances occurring at Poisson times with a geometric distribution ruling its multiplicity. The systems to which our results apply include: general piecewise expanding maps of the interval (Rychlik maps), maps with indifferent fixed points (Manneville-Pomeau maps) and Benedicks-Carleson quadratic maps.Comment: To appear in Communications in Mathematical Physic

A service-oriented architecture for integrating the modeling and formal verification of genetic regulatory networks

<p>Abstract</p> <p>Background</p> <p>The study of biological networks has led to the development of increasingly large and detailed models. Computer tools are essential for the simulation of the dynamical behavior of the networks from the model. However, as the size of the models grows, it becomes infeasible to manually verify the predictions against experimental data or identify interesting features in a large number of simulation traces. Formal verification based on temporal logic and model checking provides promising methods to automate and scale the analysis of the models. However, a framework that tightly integrates modeling and simulation tools with model checkers is currently missing, on both the conceptual and the implementational level.</p> <p>Results</p> <p>We have developed a generic and modular web service, based on a service-oriented architecture, for integrating the modeling and formal verification of genetic regulatory networks. The architecture has been implemented in the context of the qualitative modeling and simulation tool G<smcaps>NA</smcaps> and the model checkers N<smcaps>U</smcaps>SMV and C<smcaps>ADP</smcaps>. G<smcaps>NA</smcaps> has been extended with a verification module for the specification and checking of biological properties. The verification module also allows the display and visual inspection of the verification results.</p> <p>Conclusions</p> <p>The practical use of the proposed web service is illustrated by means of a scenario involving the analysis of a qualitative model of the carbon starvation response in <it>E. coli</it>. The service-oriented architecture allows modelers to define the model and proceed with the specification and formal verification of the biological properties by means of a unified graphical user interface. This guarantees a transparent access to formal verification technology for modelers of genetic regulatory networks.</p

Y-chromosome lineages from Portugal, Madeira and Açores record rlements of sephardim and berber ancestry

A total of 553 Y-chromosomes were analyzed from mainland Portugal and the North Atlantic Archipelagos of Ac¸ores and Madeira, in order to characterize the genetic composition of their male gene pool. A large majority (78–83% of each population) of the male lineages could be classified as belonging to three basic Y chromosomal haplogroups, R1b, J, and E3b. While R1b, accounting for more than half of the lineages in any of the Portuguese subpopulations, is a characteristic marker of many different West European populations, haplogroups J and E3b consist of lineages that are typical of the circum-Mediterranean region or even East Africa. The highly diverse haplogroup E3b in Portuguese likely combines sub-clades of distinct origins. The present composition of the Y chromosomes in Portugal in this haplogroup likely reflects a pre-Arab component shared with North African populations or testifies, at least in part, to the influence of Sephardic Jews. In contrast to the marginally low sub-Saharan African Y chromosome component in Portuguese, such lineages have been detected at a moderately high frequency in our previous survey of mtDNA from the same samples, indicating the presence of sex-related gene flow, most likely mediated by the Atlantic slave trade.info:eu-repo/semantics/publishedVersio

Determining factors of functioning in hemodialysis patients using the international classification of functioning, disability and health

Background: Hemodialysis (HD) treatment affects functioning, physical activity level, clinical biomarkers, and body composition. However, the association between these variables with functioning, considering International Classification of Functioning, Disability and Health (ICF) domains remains unclear. Thus, the aim of this study was to investigate the possible association between physical activity, biomarkers, and body composition with functioning in HD patients in reference to the ICF. Methods: Eighty HD patients performed different tests grouped according to ICF domain: Body structure and function – handgrip strength (HS), 5-repetition sit-to-stand test, and 60-s sit-to-stand test (5-STS, 60-STS, respectively); Activity – short physical performance battery (SPPB); and Participation – participation scale questionnaire. Physical activity [Human Activity Profile questionnaire (HAP)], body composition (Dual-energy X-ray absorptiometry), Parathormone (PTH), and alkaline phosphatase were analyzed as possible variables associated with ICF domains. Data analyses were performed using simple and multiple regression models adjusted for age, duration of HD, and diuresis volume. Results: In the body structure and function domain, appendicular lean mass, PTH level, and age were associated with HS ( R2 = 0.558); HAP and PTH were associated with 5-STS ( R2 = 0.263); and HAP, PTH, duration of HD, and age were associated with 60-STS ( R2 = 0.337). In the activity domain, HAP, PTH, alkaline phosphatase, duration of HD, age, and body fat were associated with SPPB ( R2 = 0.689). Finally, only HAP was associated with the participation scale ( R2 = 0.067). Conclusion: Physical activity and PTH levels are determinant protagonists of functioning in all ICF domains in hemodialysis patients

In situ evaluation of fluoride-, stannous- and polyphosphate-containing solutions against enamel erosion

Objective To evaluate the anti-erosive effect of solutions containing sodium fluoride (F: 225 ppm of fluoride), sodium fluoride + stannous chloride (F + Sn: 225 ppm of fluoride + 800 ppm of stannous), sodium fluoride + stannous chloride + sodium linear polyphosphate (F + Sn + LPP: 225 ppm of fluoride + 800 ppm of stannous + 2% of sodium linear polyphosphate), and deionized water (C: control), using a four-phase, single-blind, crossover in situ clinical trial. Methods In each phase, 12 volunteers wore appliances containing 4 enamel specimens, which were submitted to a 5-day erosion-remineralization phase that consisted of 2 h of salivary pellicle formation with the appliance in situ, followed by 2 min extra-oral immersion in 1% citric acid (pH 2.4), 6x/day, with 90 min of exposure to saliva in situ between the challenges. Treatment with the test solutions was performed extra-orally for 2 min, 2x/day. At the end of the experiment, surface loss (SL, in μm) was evaluated by optical profilometry. Data were analyzed using ANOVA and Tukey tests (α = 0.05). The surface of additional specimens was evaluated by x-ray diffraction after treatments (n = 3). Results C (mean SL ± standard-deviation: 5.97 ± 1.70) and F (5.36 ± 1.59) showed the highest SL, with no significant difference between them (p > 0.05). F + Sn (2.68 ± 1.62) and F + Sn + LPP (2.10 ± 0.95) did not differ from each other (p > 0.05), but presented lower SL than the other groups (P < 0.05). Apatite and stannous deposits on specimen surfaces were identified in the x-ray analysis for F + Sn and F + Sn + LPP. Conclusions Sodium fluoride solution exhibited no significant anti-erosive effect. The combination between sodium fluoride and stannous chloride reduced enamel erosion, irrespective of the presence of linear sodium polyphosphate. Clinical significance Under highly erosive conditions, sodium fluoride rinse may not be a suitable alternative to prevent enamel erosion. A rinse containing sodium fluoride and stannous chloride was shown to be a better treatment option, which was not further improved by addition of the sodium linear polyphosphate

Inspection score and grading system for food services in Brazil: the results of s food safety strategy to reduce the risk of foodborne diseases during the 2014 FIFA World Cup

In 2014, Brazil hosted one of the most popular sport competitions in the world, the FIFA World Cup. Concerned about the intense migration of tourists, the Brazilian government decided to deploy a food safety strategy based on inspection scores and a grading system applied to food services. The present study aimed to evaluate the results of the food safety strategy deployed during the 2014 FIFA World Cup in Brazil. To assess food safety, an evaluation instrument was applied twice in 1927 food service establishments from 26 cities before the start of the competition. This instrument generated a food safety score for each establishment that ranged from 0.0 (no flaws observed) to 2565.95, with four possible grades: A (0.0-13.2); B (13.3-502.6); C (502.7-1152.2); and pending (more than 1152.3). Each food service received a stamp with the grade of the second evaluation. After the end of the World Cup, a study was conducted with different groups of the public to evaluate the acceptance of the strategy. To this end, 221 consumers, 998 food service owners or managers, 150 health surveillance auditors, and 27 health surveillance coordinators were enrolled. These participants completed a survey with positive and negative responses about the inspection score system through a 5-point Likert scale. A reduction in violation scores from 393.1 to 224.4 (p < 0.001) was observed between the first and second evaluation cycles. Of the food services evaluated, 38.7% received the A stamp, 41.4% the B stamp, and 13.9% the C stamp. All positive responses on "system reliability" presented a mean of 4.0 or more, indicating that the public believed this strategy is reliable for communicating risks and promoting food safety. The strategy showed positive results regarding food safety and public acceptance. The deployed strategy promoted improvements in the food safety of food services. The implementation of a permanent policy may be well accepted by the public and may greatly contribute to a reduction in foodborne diseases (FBDs)

Inspection Score and Grading System for Food Services in Brazil: The Results of a Food Safety Strategy to Reduce the Risk of Foodborne Diseases during the 2014 FIFA World Cup

In 2014, Brazil hosted one of the most popular sport competitions in the world, the FIFA World Cup. Concerned about the intense migration of tourists, the Brazilian government decided to deploy a food safety strategy based on inspection scores and a grading system applied to food services. The present study aimed to evaluate the results of the food safety strategy deployed during the 2014 FIFA World Cup in Brazil. To assess food safety, an evaluation instrument was applied twice in 1927 food service establishments from 26 cities before the start of the competition. This instrument generated a food safety score for each establishment that ranged from 0.0 (no flaws observed) to 2565.95, with four possible grades: A (0.0-13.2)B (13.3-502.6)C (502.7-1152.2)and pending (more than 1152.3). Each food service received a stamp with the grade of the second evaluation. After the end of the World Cup, a study was conducted with different groups of the public to evaluate the acceptance of the strategy. To this end, 221 consumers, 998 food service owners or managers, 150 health surveillance auditors, and 27 health surveillance coordinators were enrolled. These participants completed a survey with positive and negative responses about the inspection score system through a 5-point Likert scale. A reduction in violation scores from 393.1 to 224.4 (p < 0.001) was observed between the first and second evaluation cycles. Of the food services evaluated, 38.7% received the A stamp, 41.4% the B stamp, and 13.9% the C stamp. All positive responses on "system reliability" presented a mean of 4.0 or more, indicating that the public believed this strategy is reliable for communicating risks and promoting food safety. The strategy showed positive results regarding food safety and public acceptance. The deployed strategy promoted improvements in the food safety of food services. The implementation of a permanent policy may be well accepted by the public and may greatly contribute to a reduction in foodborne diseases (FBDs).FUNCAMP - Fundacao de Desenvolvimento da UnicampUniv Estadual Campinas, Fac Ciencias Aplicadas, Limeira, BrazilCtr Univ Franciscano, Curso Nutr, Santa Maria, RS, BrazilUniv Fed Rio Grande do Sul, Inst Ciencia & Tecnol Alimentos, Porto Alegre, RS, BrazilUniv Fed Rio Grande do Sul, Dept Nutr, Porto Alegre, RS, BrazilAgencia Nacl Vigilancia Sanit, Brasilia, DF, BrazilUniv Fed Sao Paulo, Ctr Desenvolvimento Ensino Super Saude, Sao Paulo, BrazilUniv Fed Sao Paulo, Ctr Desenvolvimento Ensino Super Saude, Sao Paulo, BrazilFUNCAMP: 2169/16Web of Scienc

Asymmetric introgression between sympatric molestus and pipiens forms of Culex pipiens (Diptera: Culicidae) in the Comporta region, Portugal

<p>Abstract</p> <p>Background</p> <p><it>Culex pipiens </it>L. is the most widespread mosquito vector in temperate regions. This species consists of two forms, denoted molestus and pipiens, that exhibit important behavioural and physiological differences. The evolutionary relationships and taxonomic status of these forms remain unclear. In northern European latitudes molestus and pipiens populations occupy different habitats (underground <it>vs</it>. aboveground), a separation that most likely promotes genetic isolation between forms. However, the same does not hold in southern Europe where both forms occur aboveground in sympatry. In these southern habitats, the extent of hybridisation and its impact on the extent of genetic divergence between forms under sympatric conditions has not been clarified. For this purpose, we have used phenotypic and genetic data to characterise <it>Cx. pipiens </it>collected aboveground in Portugal. Our aims were to determine levels of genetic differentiation and the degree of hybridisation between forms occurring in sympatry, and to relate these with both evolutionary and epidemiological tenets of this biological group.</p> <p>Results</p> <p>Autogeny and stenogamy was evaluated in the F1 progeny of 145 individual <it>Cx. pipiens </it>females. Bayesian clustering analysis based on the genotypes of 13 microsatellites revealed two distinct genetic clusters that were highly correlated with the alternative traits that define pipiens and molestus. Admixture analysis yielded hybrid rate estimates of 8-10%. Higher proportions of admixture were observed in pipiens individuals suggesting that more molestus genes are being introgressed into the pipiens form than the opposite.</p> <p>Conclusion</p> <p>Both physiological/behavioural and genetic data provide evidence for the sympatric occurrence of molestus and pipiens forms of <it>Cx. pipiens </it>in the study area. In spite of the significant genetic differentiation between forms, hybridisation occurs at considerable levels. The observed pattern of asymmetric introgression probably relates to the different mating strategies adopted by each form. Furthermore, the differential introgression of molestus genes into the pipiens form may induce a more opportunistic biting behaviour in the latter thus potentiating its capacity to act as a bridge-vector for the transmission of arboviral infections.</p