Molecular evolution of a malaria resistance gene (DARC) in primates

Genes involved in host-pathogen interactions are often strongly affected by positive natural selection. The Duffy antigen, coded by the Duffy antigen receptor for chemokines (DARC) gene, serves as a receptor for Plasmodium vivax in humans and for Plasmodium knowlesi in some nonhuman primates. In the majority of sub-Saharan Africans, a nucleic acid variant in GATA-1 of the gene promoter is responsible for the nonexpression of the Duffy antigen on red blood cells and consequently resistance to invasion by P. vivax. The Duffy antigen also acts as a receptor for chemokines and is expressed in red blood cells and many other tissues of the body. Because of this dual role, we sequenced a 3,000-bp region encompassing the entire DARC gene as well as part of its 5' and 3' flanking regions in a phylogenetic sample of primates and used statistical methods to evaluate the nature of selection pressures acting on the gene during its evolution. We analyzed both coding and regulatory regions of the DARC gene. The regulatory analysis showed accelerated rates of substitution at several sites near known motifs. Our tests of positive selection in the coding region using maximum likelihood by branch sites and maximum likelihood by codon sites did not yield statistically significant evidence for the action of positive selection. However, the maximum likelihood test in which the gene was subdivided into different structural regions showed that the known binding region for P. vivax/P. knowlesi is under very different selective pressures than the remainder of the gene. In fact, most of the gene appears to be under strong purifying selection, but this is not evident in the binding region. We suggest that the binding region is under the influence of two opposing selective pressures, positive selection possibly exerted by the parasite and purifying selection exerted by chemokines.

Relaxation of Adaptive Evolution during the HIV-1 Infection Owing to Reduction of CD4+T Cell Counts

Background: The first stages of HIV-1 infection are essential to establish the diversity of virus population within host. It has been suggested that adaptation to host cells and antibody evasion are the leading forces driving HIV evolution at the initial stages of AIDS infection. In order to gain more insights on adaptive HIV-1 evolution, the genetic diversity was evaluated during the infection time in individuals contaminated by the same viral source in an epidemic cluster. Multiple sequences of V3 loop region of the HIV-1 were serially sampled from four individuals: comprising a single blood donor, two blood recipients, and another sexually infected by one of the blood recipients. The diversity of the viral population within each host was analyzed independently in distinct time points during HIV-1 infection. Results: Phylogenetic analysis identified multiple HIV-1 variants transmitted through blood transfusion but the establishing of new infections was initiated by a limited number of viruses. Positive selection (d(N)/d(S)>1) was detected in the viruses within each host in all time points. In the intra-host viruses of the blood donor and of one blood recipient, X4 variants appeared respectively in 1993 and 1989. In both patients X4 variants never reached high frequencies during infection time. The recipient, who X4 variants appeared, developed AIDS but kept narrow and constant immune response against HIV-1 during the infection time. Conclusion: Slowing rates of adaptive evolution and increasing diversity in HIV-1 are consequences of the CD4+ T cells depletion. The dynamic of R5 to X4 shift is not associated with the initial amplitude of humoral immune response or intensity of positive selection.

The antimicrobial effect of new and conventional endodontic irrigants on intra-orally infected dentin

Objectives. To evaluate if the incorporation of antimicrobial compounds to chelating agents or the use of chelating agents with antimicrobial activity as 7% maleic acid and peracetic acid show similar disinfection ability in comparison to conventional irrigants as sodium hypochlorite or iodine potassium iodide against biofilms developed on dentin. Materials and methods. The total bio-volume of live cells, the ratio of live cells and the substratum coverage of dentin infected intra-orally and treated with the irrigant solutions: MTAD, Qmix, Smear Clear, 7% maleic acid, 2% iodine potassium iodide, 4% peracetic acid, 2.5% and 5.25% sodium hypochlorite was measured by using confocal microscopy and the live/dead technique. Five samples were used for each irrigant solution. Results. Several endodontic irrigants containing antimicrobials as clorhexidine (Qmix), cetrimide (Smear Clear), maleic acid, iodine compounds or antibiotics (MTAD) lacked an effective antibiofilm activity when the dentin was infected intra-orally. The irrigant solutions 4% peracetic acid and 2.5–5.25% sodium hypochlorite decrease significantly the number of live bacteria in biofilms, providing also cleaner dentin surfaces (p < 0.05). Conclusions. Several chelating agents containing antimicrobials could not remove nor kill significantly biofilms developed on intra-orally infected dentin, with the exception of sodium hypochlorite and 4% peracetic acid. Dissolution ability is mandatory for an appropriate eradication of biofilms attached to dentin.

Signal transduction in Plasmodium-Red Blood Cells interactions and in cytoadherence

Malaria is responsible for more than 1.5 million deaths each year, especially among children (Snow et al. 2005). Despite of the severity of malaria situation and great effort to the development of new drug targets (Yuan et al. 2011) there is still a relative low investment toward antimalarial drugs. Briefly there are targets classes of antimalarial drugs currently being tested including: kinases, proteases, ion channel of GPCR, nuclear receptor, among others (Gamo et al. 2010). Here we review malaria signal transduction pathways in Red Blood Cells (RBC) as well as infected RBCs and endothelial cells interactions, namely cytoadherence. The last process is thought to play an important role in the pathogenesis of severe malaria. The molecules displayed on the surface of both infected erythrocytes (IE) and vascular endothelial cells (EC) exert themselves as important mediators in cytoadherence, in that they not only induce structural and metabolic changes on both sides, but also trigger multiple signal transduction processes, leading to alteration of gene expression, with the balance between positive and negative regulation determining endothelial pathology during a malaria infection.

The complex construction of psychological identities in Palestine: Integrating narratives and life experiences

Palestinian youth is challenged by multiple discourses in the process of constitution of its identity. This discursive multiplicity, characteristic of contemporary global societies, is confronted with personal life experiences, giving meaning to primarily nebulous affective impacts in the social environment. Starting from a semiotic-cultural perspective in cultural psychology one can establish a link between the notion of master narrative used by Hammack (2010) and the notion of myth-using the conception of ideology as a bridge that articulates both. Antinomies in the self-biographic narratives presented and discussed by Hammack (2010) support the master narrative of Palestinian identity and enter into interactions with other psychological identities of the interviewed youngsters, such as their religious tradition and secular education. Symbolic elements that are brought to the identity-making process by the diverse narratives are to be seen as resources for the comprehension of life experiences, demanding an integrative effort in the face of what is known and unknown in relation to alterity.

Relative abundance and population biology of the non-indigenous crab Charybdis hellerii (Crustacea: Brachyura: Portunidae) in a southwestern Atlantic estuary-bay complex

Invasive species are potential threats to biodiversity, especially if they become established and outnumber native species. In this study, a population of the non-indigenous crab Charybdis hellerii was analyzed in an estuary-bay complex on the southeastern Brazilian coast, with respect to its abundance relative to sympatric native brachyuran species, as well as the size structure, sexual maturity, sex ratio, frequency of mutilation, reproductive period, and development of the reproductive system. Crabs were sampled monthly both in the intertidal zone of rocky shores and on sublittoral soft-bottom. Nine species were recorded on the rocky shores, where C. hellerii was the second most abundant species; only three individuals of C. hellerii were collected in the sublittoral samples. This population of C. hellerii showed a unimodal size structure composed mainly of mature individuals; males were larger than females, and the sex ratio was skewed toward males (3.1:1). About 46.9% of the individuals (75 of 160 crabs) had mutilated or regenerating appendages, more frequent in males (56.8%) than in females (28.2%), which may reflect both inter- and intraspecific agonistic interactions. A continuous reproductive pattern is suggested for this population, although ovigerous females occurred unevenly during the year, with 58.82% of them being collected in winter. There was evidence of multiple spawning, since the ovigerous females with an initial egg mass showed mature ovaries as well as seminal receptacles filled with sperm. C. hellerii is well established in the estuary-bay complex, but is concentrated in intertidal and shallow subtidal rocky shores, where it may compete with and replace other species such as the portunid Cronius ruber. This study also highlights the importance of systematic monitoring studies to evaluate the effects of the introduction of non-indigenous species on ecologically similar natives.

Capillary electrophoretic enantioselective determination of zopiclone and its impurities

A capillary electrophoretic enantioselective method with UV detection was developed and validated for the simultaneous quantification of zopiclone enantiomers and its impurities, zopiclone-N-oxide enantiomers, and 2-amino-5-chloropyridine, in tablets. The analytes were extracted from the tablets using ACN and were separated in an uncoated fused-silica capillary (50 mu m, 42 cm effective length, 50 cm total length) using 80 mM sodium phosphate buffer pH 2.5 and 5 mM carboxymethyl-beta-cyclodextrin as running buffer. The analytes and the internal standard (trimethoprim) were detected at 305 and 200 nm, respectively. A voltage of 27 kV was applied and the capillary temperature was maintained at 25 degrees C. All enantiomers were analyzed within 8 min and linear calibration curves over the concentration range of 0.40.8 mg mL-1 for each zopiclone enantiomer, 0.81.6 mu g mL-1 for 2-amino-5-chloropyridine and 0.40.8 mu g mL-1 for each zopiclone-N-oxide enantiomer were obtained. The coefficients of correlation obtained for the linear curves were greater than 0.99. The intra-day and inter-day accuracy and precision were lower than 2% for all analytes. This validated method was employed to study the degradation and racemization of zopiclone under stress conditions. This application demonstrated the importance of a stability-indicating assay method for this drug.

Epidemiological aspects of tuberculosis in children and adolescents in Rio de Janeiro

Objective: To describe the epidemiological aspects of childhood tuberculosis (TB) in a Brazilian reference hospital. Methods: This was a retrospective study (1999-2008) of 473 subjects (0-14 year olds) with confirmed TB, or with clinical improvement by the fourth month of treatment under the unit's care, including the review of medical records, monitoring reports and notifications by the TB unit. Results: Among 473 TB cases included in the study, positive tuberculin skin test was observed in 52%, history of contact with a patient with pulmonary tuberculosis in 66%, mostly intra-household, and with the father/stepfather most commonly involved; and disseminated TB in 22%. The result of HIV testing was obtained in 265 (56%) cases, being positive in 45 (17%). The diagnosis of TB was confirmed in 31% of cases, most frequently in children older than 5 years, with negative tuberculin skin test, and in disseminated forms. Of the 65 cultures positive for TB performed in the study, drug sensitivity testing to anti-TB drugs was done in 30 (46%) clinical samples, among which 10 (33%) were resistant to one or more anti-TB drugs, and 2 (0.8%) were multi-drug-resistant. Among patients with confirmed pulmonary TB, 31% did not meet the criteria for starting anti-TB treatment according to the scores of the Ministry of Health (<= 25 points). Conclusion: The high proportion of drug-resistant TB and co-infection with HIV identified in this study highlight the necessity to carry out additional studies in order to evaluate the impact of TB control activities on childhood TB.

Effective carrying capacity and analytical solution of a particular case of the Richards-like two-species population dynamics model

We consider a generalized two-species population dynamic model and analytically solve it for the amensalism and commensalism ecological interactions. These two-species models can be simplified to a one-species model with a time dependent extrinsic growth factor. With a one-species model with an effective carrying capacity one is able to retrieve the steady state solutions of the previous one-species model. The equivalence obtained between the effective carrying capacity and the extrinsic growth factor is complete only for a particular case, the Gompertz model. Here we unveil important aspects of sigmoid growth curves, which are relevant to growth processes and population dynamics. (C) 2011 Elsevier B.V. All rights reserved.

Antioxidant Effects of Quercetin and Catechin Encapsulated into PLGA Nanoparticles

Polymeric nanoparticles (PLGA) have been developed for the encapsulation and controlled release of quercetin and catechin. Nanoparticles were fabricated using a solvent displacementmethod. Physicochemical properties were measured by light scattering, scanning electron microscopy and zeta-potential, X-ray diffraction, infrared spectroscopy and differential scanning calorimetry. Encapsulation efficiency and in vitro release profiles were obtained from differential pulse voltammetry experiments. Antioxidant properties of free and encapsulated flavonoids were determined by TBARS, fluorescence spectroscopy and standard chelating activity methods. Relatively small (d approximate to 400 nm) polymeric nanoparticles were obtained containing quercetin or catechin in a non-crystalline form (EE approximate to 79%) and the main interactions between the polymer and each flavonoid were found to consist of hydrogen bonds. In vitro release profiles were pH-dependant, the more acidic pH, the faster release of each flavonoid from the polymeric nanoparticles. The inhibition of the action of free radicals and chelating properties, were also enhanced when quercetin and catechin were encapsulated within PLGA nanoparticles. The information obtained from this study will facilitate the design and fabrication of polymeric nanoparticles as possible oral delivery systems for encapsulation, protection and controlled release of flavonoids aimed to prevent oxidative stress in human body or food products.

Burden of maternal bipolar disorder on at-risk offspring: A controlled study on family planning and maternal care

Introduction: Bipolar disorder (BD) is a highly incapacitating disease typically associated with high rates of familial dysfunction. Despite recent literature suggesting that maternal care is an important environmental factor in the development of behavioral disorders, it is unclear how much maternal care is dysfunctional in BD subjects. Objective: The objective of this study was to characterize maternal care in DSM-IV/SCID diagnosed BD type I subjects compared to healthy controls with (PD) and without (NPD) other psychiatric diagnoses. Materials and methods: Thirty-four BD mothers and 106 controls underwent an interview about family planning and maternal care, obstetrical complications, and mother-child interactions. K-SADS-PL questions about violence exposure were used to ascertain domestic violence and physical/sexual abuse. Results: BD mothers were less likely to have stable unions (45.5%; p < 0.01) or to live with the biological father of their children (33.3%; p < 0.01), but had higher educational level and higher rates of social security use/retirement. They also had fewer children and used less contraceptive methods than controls. Children of BD women had higher rates of neonatal anoxia, and reported more physical abuse (16.1%; p = 0.02) than offspring of NPD mothers. Due to BD mothers' symptoms, 33.3% of offspring suffered physical and/or psychological abuse. Limitations: Post hoc analysis, and the use of questions as a surrogate of symptoms as opposed to validated instruments. Conclusion: This is one of few reports confirming that maternal care given by BD women is dysfunctional. BD psychopathology can lead to poor maternal care and both should be considered important environmental risk factors in BD, suggesting that BD psychoeducation should include maternal care orientation. (C) 2012 Elsevier B.V. All rights reserved.

Genotoxic and mutagenic effects of erythrosine B, a xanthene food dye, on HepG2 cells

Erythrosine (ErB) is a xanthene and an US Food and Drug Administration approved dye used in foods, drugs and cosmetics. Although its utilization is permitted, ErB is described as inhibitor of enzymes and protein-protein interactions and is toxic to pituitary and spermatogenesis processes. However, the genotoxicity and mutagenicity of ErB is inconclusive in the literature. This study aimed to analyze the genotoxicity of this dye using the alkaline comet assay and is the first investigation to evaluate ErB mutagenicity using the cytokinesis block micronucleus cytome (CBMN-Cyt) assay in HepG2 cells. These cells were chosen because they produce phase I and phase II enzymes that can mimic in vivo metabolism. The cells were treated with seven concentrations (0.1-70.0 mu g mL(-1)) of ErB, and the results showed genotoxicity at the two highest concentrations and mutagenicity at six concentrations. Furthermore, as micronuclei result from clastogenic and aneugenic processes, while comet assay is often considered more sensitive and detects DNA single strain breaks, we suggest that an aneugenic is responsible for the observed damage. Although ErB is approved for use in the food, cosmetic and pharmaceutical industries, it must be used carefully because it damages the DNA structure. (C) 2012 Elsevier Ltd. All rights reserved.

The use of body circumferences for the prediction of intra-abdominal fat in obese women with polycystic ovary syndrome

Introduction: Computerizd tomography (CT) is the gold standard for the evaluation of intra- (IAF) and total (TAF) abdominal fat; however, the high cost of the procedure and exposure to radiation limit its routine use. Objective: To develop equations that utilize anthropometric measures for the estimate of IAF and TAF in obese women with polycystic ovary syndrome (PCOS). Methods: The weight, height, BMI, and abdominal (AC), waist (WC), chest (CC), and neck (NC) circumferences of thirty obese women with PCOS were measured, and their IAF and TAF were analyzed by CT. Results: The anthropometric variables AC, CC, and NC were chosen for the TAF linear regression model because they were better correlated with the fat deposited in this region. The model proposed for TAF (predicted) was: 4.63725 + 0.01483 x AC - 0.00117 x NC - 0.00177 x CC (R-2 = 0.78); and the model proposed for IAF was: IAF (predicted) = 1.88541 + 0.01878 x WC + 0.05687 x NC - 0.01529 x CC (R-2 = 0.51). AC was the only independent predictor of TAF (p < 0.01). Conclusion: The equations proposed showed good correlation with the real value measured by CT, and can be used in clinical practice. (Nutr Hosp. 2012;27:1662-1666) DOI:10.3305/nh.2012.27.5.5933

Three-dimensional solitons in cross-combined linear and nonlinear optical lattices

The existence and stability of three-dimensional (3D) solitons, in cross-combined linear and nonlinear optical lattices, are investigated. In particular, with a starting optical lattice (OL) configuration such that it is linear in the x-direction and nonlinear in the y-direction, we consider the z-direction either unconstrained (quasi-2D OL case) or with another linear OL (full 3D case). We perform this study both analytically and numerically: analytically by a variational approach based on a Gaussian ansatz for the soliton wavefunction and numerically by relaxation methods and direct integrations of the corresponding Gross-Pitaevskii equation. We conclude that, while 3D solitons in the quasi-2D OL case are always unstable, the addition of another linear OL in the z-direction allows us to stabilize 3D solitons both for attractive and repulsive mean interactions. From our results, we suggest the possible use of spatial modulations of the nonlinearity in one of the directions as a tool for the management of stable 3D solitons.

In situ effect of sodium fluoride or titanium tetrafluoride varnish and solution on carious demineralization of enamel

This study evaluated the effect of titanium tetrafluoride (TiF4) formulations on enamel carious demineralization in situ. Thirteen subjects took part in this cross-over, split-mouth, double-blind study performed in three phases of 14 d each. In each subject, two sound and two predemineralized specimens of bovine enamel were worn intra-orally and plaque accumulation was allowed. One sound and one predemineralized specimen in each subject was treated once with sodium fluoride (NaF) varnish or solution (Treatment A); TiF4 varnish or solution (Treatment B); or placebo varnish or no treatment (Treatment C). The initially sound enamel specimens were exposed to severe cariogenic challenge (20% sucrose, eight times daily for 5 min each time), whereas the predemineralized specimens were not. Eleven subjects were able to finish all experimental phases. The enamel alterations were quantified by surface hardness and transversal microradiography. Demineralization of previously sound enamel was reduced by all test formulations except for the NaF solution, while both TiF4 formulations were as effective as NaF varnish. For the predemineralized specimens, enamel surface hardness was increased only by TiF4 formulations, while subsurface mineral remineralization could not be seen in any group. Within the experimental protocol, TiF4 was able to decrease enamel demineralization to a similar degree as NaF varnish under severe cariogenic challenges, while only TiF4 formulations remineralized the enamel surface.