Genome-wide SNP genotyping highlights the role of natural selection in Plasmodium falciparum population divergence

Background: The malaria parasite Plasmodium falciparum exhibits abundant genetic diversity, and this diversity is key to its success as a pathogen. Previous efforts to study genetic diversity in P. falciparum have begun to elucidate the demographic history of the species, as well as patterns of population structure and patterns of linkage disequilibrium within its genome. Such studies will be greatly enhanced by new genomic tools and recent large-scale efforts to map genomic variation. To that end, we have developed a high throughput single nucleotide polymorphism (SNP) genotyping platform for P. falciparum. Results: Using an Affymetrix 3,000 SNP assay array, we found roughly half the assays (1,638) yielded high quality, 100% accurate genotyping calls for both major and minor SNP alleles. Genotype data from 76 global isolates confirm significant genetic differentiation among continental populations and varying levels of SNP diversity and linkage disequilibrium according to geographic location and local epidemiological factors. We further discovered that nonsynonymous and silent (synonymous or noncoding) SNPs differ with respect to within-population diversity, interpopulation differentiation, and the degree to which allele frequencies are correlated between populations. Conclusions: The distinct population profile of nonsynonymous variants indicates that natural selection has a significant influence on genomic diversity in P. falciparum, and that many of these changes may reflect functional variants deserving of follow-up study. Our analysis demonstrates the potential for new high-throughput genotyping technologies to enhance studies of population structure, natural selection, and ultimately enable genome-wide association studies in P. falciparum to find genes underlying key phenotypic traits.

Nonquadratic gauge fixing and global gauge invariance in the effective action

The possibility of having a gauge fixing term in the effective Lagrangian that is not a quadratic expression has been explored in spin-two theories so as to have a propagator that is both traceless and transverse. We first show how this same approach can be used in spontaneously broken gauge theories as an alternate to the 't Hooft gauge fixing which avoids terms quadratic in the scalar fields. This ""nonquadratic"" gauge fixing in the effective action results in two complex fermionic and one real bosonic ghost field. A global gauge invariance involving a fermionic gauge parameter, analogous to the usual Becchi-Rouet-Stora-Tyutin invariance, is present in this effective action.

Ambiguities in the effective action in Lorentz-violating gravity

We investigate the occurrence of ambiguities for the Lorentz-violating gravitational Chern-Simons term. It turns out that this term is accompanied by a coefficient depending on an undetermined parameter, due to an arbitrariness in the choice of the conserved current.

Antimicrobial photodynamic action on dentin using a light-emitting diode light source

Objective: The aim of this study was the evaluation of two different photosensitizers activated by red light emitted by light-emitting diodes (LEDs) in the decontamination of carious bovine dentin. Materials and Methods: Fifteen bovine incisors were used to obtain dentin samples which were immersed in brain-heart infusion culture medium supplemented with 1% glucose, 2% sucrose, and 1% young primary culture of Lactobacillus acidophilus 108 CFU/mL and Streptococcus mutans 108 CFU/mL for caries induction. Three different concentrations of the Photogem solution, a hematoporphyrin derivative (1, 2, and 3 mg/mL) and two different concentrations of toluidine blue O (TBO), a basic dye (0.025 and 0.1 mg/mL) were used. To activate the photosensitizers two different light exposure times were used: 60 sec and 120 sec, corresponding respectively to the doses of 24 J/cm(2) and 48 J/cm(2). Results: After counting the numbers of CFU per milligram of carious dentin, we observed that the use of LED energy in association with Photogem or TBO was effective for bacterial reduction in carious dentin, and that the greatest effect on S. mutans and L. acidophilus was obtained with TBO at 0.1 mg/mL and a dose of 48 J/cm(2). It was also observed that the overall toxicity of TBO was higher than that of Photogem, and that the phototoxicity of TBO was higher than that of Photogem. Conclusion: Based on our data we propose a mathematical model for the photodynamic effect when different photosensitizer concentrations and light doses are used.

Feature selection environment for genomic applications

Background: Feature selection is a pattern recognition approach to choose important variables according to some criteria in order to distinguish or explain certain phenomena (i.e., for dimensionality reduction). There are many genomic and proteomic applications that rely on feature selection to answer questions such as selecting signature genes which are informative about some biological state, e. g., normal tissues and several types of cancer; or inferring a prediction network among elements such as genes, proteins and external stimuli. In these applications, a recurrent problem is the lack of samples to perform an adequate estimate of the joint probabilities between element states. A myriad of feature selection algorithms and criterion functions have been proposed, although it is difficult to point the best solution for each application. Results: The intent of this work is to provide an open-source multiplataform graphical environment for bioinformatics problems, which supports many feature selection algorithms, criterion functions and graphic visualization tools such as scatterplots, parallel coordinates and graphs. A feature selection approach for growing genetic networks from seed genes ( targets or predictors) is also implemented in the system. Conclusion: The proposed feature selection environment allows data analysis using several algorithms, criterion functions and graphic visualization tools. Our experiments have shown the software effectiveness in two distinct types of biological problems. Besides, the environment can be used in different pattern recognition applications, although the main concern regards bioinformatics tasks.

Context tree selection: A unifying view

Context tree models have been introduced by Rissanen in [25] as a parsimonious generalization of Markov models. Since then, they have been widely used in applied probability and statistics. The present paper investigates non-asymptotic properties of two popular procedures of context tree estimation: Rissanen's algorithm Context and penalized maximum likelihood. First showing how they are related, we prove finite horizon bounds for the probability of over- and under-estimation. Concerning overestimation, no boundedness or loss-of-memory conditions are required: the proof relies on new deviation inequalities for empirical probabilities of independent interest. The under-estimation properties rely on classical hypotheses for processes of infinite memory. These results improve on and generalize the bounds obtained in Duarte et al. (2006) [12], Galves et al. (2008) [18], Galves and Leonardi (2008) [17], Leonardi (2010) [22], refining asymptotic results of Buhlmann and Wyner (1999) [4] and Csiszar and Talata (2006) [9]. (C) 2011 Elsevier B.V. All rights reserved.

Bothrops jararaca Peptide with Anti-Hypertensive Action Normalizes Endothelium Dysfunction Involved in Physiopathology of Preeclampsia

Preeclampsia, a pregnancy-specific syndrome characterized by hypertension, proteinuria and edema, is a major cause of fetal and maternal morbidity and mortality especially in developing countries. Bj-PRO-10c, a proline-rich peptide isolated from Bothrops jararaca venom, has been attributed with potent anti-hypertensive effects. Recently, we have shown that Bj-PRO-10c-induced anti-hypertensive actions involved NO production in spontaneous hypertensive rats. Using in vitro studies we now show that Bj-PRO-10c was able to increase NO production in human umbilical vein endothelial cells from hypertensive pregnant women (HUVEC-PE) to levels observed in HUVEC of normotensive women. Moreover, in the presence of the peptide, eNOS expression as well as argininosuccinate synthase activity, the key rate-limiting enzyme of the citrulline-NO cycle, were enhanced. In addition, excessive superoxide production due to NO deficiency, one of the major deleterious effects of the disease, was inhibited by Bj-PRO-10c. Bj-PRO-10c induced intracellular calcium fluxes in both, HUVEC-PE and HUVEC, which, however, led to activation of eNOS expression only in HUVEC-PE. Since Bj-PRO-10c promoted biological effects in HUVEC from patients suffering from the disorder and not in normotensive pregnant women, we hypothesize that Bj-PRO-10c induces its anti-hypertensive effect in mothers with preeclampsia. Such properties may initiate the development of novel therapeutics for treating preeclampsia.

Interference with Hemozoin Formation Represents an Important Mechanism of Schistosomicidal Action of Antimalarial Quinoline Methanols

Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN), quinidine (QND) and quinacrine (QCR) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11(th) to 17(th) day after infection caused significant decreases in worm burden (39%-61%) and egg production (42%-98%). Hz formation was significantly inhibited (40%-65%) in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a valid chemotherapeutic target to treat schistosomiasis.

Molecular and morphological characterization of Amathia distans Busk and Amathia brasiliensis Busk (Bryozoa: Ctenostomata) from the tropical and subtropical Western Atlantic

Morphological and molecular analyses have proven to be complementary tools of taxonomic information for the redescription of the ctenostome bryozoans Amathia brasiliensis Busk, 1886 and Amathia distans Busk, 1886. The two species, originally described from material collected by the `Challenger` expedition but synonymized by later authors, now have their status fixed by means of the selection of lectotypes, morphological observations and analyses of DNA sequences described here. The morphological characters allowing the identification of living and/or preserved specimens are (1) A. brasiliensis: whitish-pale pigment spots in the frontal surface of stolons and zooids, and a wide stolon with biserial zooid clusters growing in clockwise and anti-clockwise spirals along it, the spirality direction being maintained from maternal to daughter stolons; and (2) A. distans: bright yellow pigment spots in stolonal and zooidal surfaces including lophophores, and a slender stolon, thickly cuticularized, with biserial zooid clusters growing in clockwise and anti-clockwise spirals along it and the spirality direction not maintained from maternal to daughter stolons. Pairwise comparisons of DNA sequences of the mitochondrial genes cytochrome c oxidase subunit I and large ribosomal RNA subunit revealed deep genetic divergence between A. brasiliensis and A. distans. Finally, analyses of those sequences within a Bayesian phylogenetic context recovered their genealogical species status.

Museum, object and information

This text aims to approach museums` role in the production of knowledge and how objects are transformed into documents when museums incorporate them. On accepting the effects of such transformation, museums start working not only with material goods, but also symbolic goods. The collection manager or exhibition curator communicate through documents rather than bringing into light its intrinsic content. In this sense, every process involving museum documents, from the selection of collections to exhibitions, has a rhetoric and ideological nature which is given. Museums must search for meanings through correlations established in the process of producing information. Exhibitions should present objects in multiple contexts, giving visitors the opportunity to participate and attribute their own meanings to them.

Anthropometric characteristics and motor skills in talent selection and development in indoor soccer

Kick performance, anthropometric characteristics, slalom, and linear running were assessed in 49 (24 elite, 25 nonelite) postpubertal indoor soccer players in order to (a) verify whether anthropometric characteristics and physical and technical capacities can distinguish players of different competitive levels, (b) compare the kicking kinematics of these groups, with and without a defined target, and (c) compare results on the assessments and coaches` subjective rankings of the players. Thigh circumference and specific technical capacities differentiated the players by level of play; cluster analysis correctly classified 77.5% of the players. The correlation between players` standardized measures and the coaches` rankings was 0.29. Anthropometric characteristics and physical capacities do not necessarily differentiate players at post-pubertal stages and should not be overvalued during early development. Considering the coaches` rankings, performance measures outside the specific game conditions may not be useful in identification of talented players.

Inhibitory action of toxic compounds present in lignocellulosic hydrolysates on xylose to xylitol bioconversion by Candida guilliermondii

The inhibitory action of acetic acid, ferulic acid, and syringaldehyde on metabolism of Candida guilliermondii yeast during xylose to xylitol bioconversion was evaluated. Assays were performed in buffered and nonbuffered semidefined medium containing xylose as main sugar (80.0 g/l), supplemented or not with acetic acid (0.8-2.6 g/l), ferulic acid (0.2-0.6 g/l), and/or syringaldehyde (0.3-0.8 g/l), according to a 2(3) full factorial design. Since only individual effects of the variables were observed, assays were performed in a next step in semidefined medium containing different concentrations of each toxic compound individually, for better understanding of their maximum concentration that can be present in the fermentation medium without affecting yeast metabolism. It was concluded that acetic acid, ferulic acid, and syringaldehyde are compounds that may affect Candida guilliermondii metabolism (mainly cell growth) during bioconversion of xylose to xylitol. Such results are of interest and reveal that complete removal of toxic compounds from the fermentation medium is not necessary to obtain efficient conversion of xylose to xylitol by Candida guilliermondii. Fermentation in buffered medium was also considered as an alternative to overcome the inhibition caused by these toxic compounds, mainly by acetic acid.

Raspberry (Rubus idaeus L.) wine: Yeast selection, sensory evaluation and instrumental analysis of volatile and other compounds

To evaluate the potential for fermentation of raspberry pulp, sixteen yeast strains (S. cerevisiae and S. bayanus) were studied. Volatile compounds were determined by GC-MS, GC-FID, and GC-PFPD. Ethanol. glycerol and organic acids were determined by HPLC. HPLC-DAD was used to analyse phenolic acids. Sensory analysis was performed by trained panellists. After a screening step, CAT-1, UFLA FW 15 and S. bayanus CBS 1505 were previously selected based on their fermentative characteristics and profile of the metabolites identified. The beverage produced with CAT-1 showed the highest volatile fatty acid concentration (1542.6 mu g/L), whereas the beverage produced with UFLA FIN 15 showed the highest concentration of acetates (2211.1 mu g/L) and total volatile compounds (5835 mu g/L). For volatile sulphur compounds. 566.5 mu g/L were found in the beverage produced with S. bayanus CBS 1505. The lowest concentration of volatile sulphur compounds (151.9 mu g/L) was found for the beverage produced with UFLA FW 15. In the sensory analysis, the beverage produced with UFLA FW 15 was characterised by the descriptors raspberry, cherry, sweet, strawberry, floral and violet. In conclusion, strain UFLA FW 15 was the yeast that produced a raspberry wine with a good chemical and sensory quality. (C) 2010 Elsevier Ltd. All rights reserved.

Extending the kinetic solution of the classic Michaelis-Menten model of enzyme action

The principal aim of studies of enzyme-mediated reactions has been to provide comparative and quantitative information on enzyme-catalyzed reactions under distinct conditions. The classic Michaelis-Menten model (Biochem Zeit 49:333, 1913) for enzyme kinetic has been widely used to determine important parameters involved in enzyme catalysis, particularly the Michaelis-Menten constant (K (M) ) and the maximum velocity of reaction (V (max) ). Subsequently, a detailed treatment of the mechanisms of enzyme catalysis was undertaken by Briggs-Haldane (Biochem J 19:338, 1925). These authors proposed the steady-state treatment, since its applicability was constrained to this condition. The present work describes an extending solution of the Michaelis-Menten model without the need for such a steady-state restriction. We provide the first analysis of all of the individual reaction constants calculated analytically. Using this approach, it is possible to accurately predict the results under new experimental conditions and to characterize and optimize industrial processes in the fields of chemical and food engineering, pharmaceuticals and biotechnology.

Selection of new glass-forming compositions in Al-La system using a combination of topological instability and thermodynamic criteria

A combination of an extension of the topological instability ""lambda criterion"" and a thermodynamic criterion were applied to the Al-La system, indicating the best range of compositions for glass formation. Alloy compositions in this range were prepared by melt-spinning and casting in an arc-melting furnace with a wedge-section copper mold. The GFA of these samples was evaluated by X-ray diffraction, differential scanning calorimetry and scanning electron microscopy. The results indicated that the gamma* parameter of compositions with high GFA is higher, corresponding to a range in which the lambda parameter is greater than 0.1, which are compositions far from Al solid solution. A new alloy was identified with the best GFA reported so far for this system, showing a maximum thickness of 286 mu m in a wedge-section copper mold. Crown Copyright (C) 2009 Published by Elsevier B.V. All rights reserved.