Insecticidal and Repellent Activity of Siparuna guianensis Aubl. (Negramina) against Aedes aegypti and Culex quinquefasciatus

This study investigated the toxic effects of essential oils isolated from Siparuna guianensis against Aedes aegypti, Culex quinquefasciatus (eggs, larvae, pupae, and adult) and Aedes albopictus (C6/36) cells. The oviposition-deterring activity, egg viability, and repellence activity in the presence of different essential oils concentrations were determined. The essential oils showed high toxicity to all developmental stages of A. aegypti and C. quinquefasciatus. Furthermore, the oils also showed high repellent activity towards the adult stage of mosquitoes (0.025 to 0.550 μg/cm2 skin conferred 100% repellence up to 120 min) and in contact with cultured insect cells (C6/36) induced death possibly by necrosis. The results presented in this work show the potential of S. guianensis essential oils for the development of an alternative and effective method for the natural control of mosquitoes in homes and urban areas.     

Direct evidence for intra- and intermolecular disulfide bond formation in the human glucocorticoid receptor. Inhibition of DNA binding and identification of a new receptor-associated protein

We have investigated the potential for the steroid affinity-labeled human glucocorticoid receptor to form both intramolecular and intermolecular disulfide bonds. Glucocorticoid receptors labeled in intact HeLa S3 cells with the covalent affinity label [3H]dexamethasone mesylate ([3H]DM) were analyzed on denaturing 5-12% polyacrylamide gels under both nonreducing and reducing conditions. Under nonreducing conditions the affinity-labeled receptor migrated as a heterogeneous species having an average molecular mass of approximately 96 kDa whereas, under reducing conditions, the receptor migrated as a more discrete form. These data suggest that a reducing environment can influence the structure of the glucocorticoid receptor monomer and further imply that sulfhydryl groups within the affinity-labeled receptor are available for modification. To pursue this observation in greater detail, we tested the effect of oxidizing conditions on the structure of the glucocorticoid receptor. The presence of low concentrations (0.125-0.5 mM) of three oxidizing reagents (sodium tetrathionate, disulfiram, and iodosobenzoate) altered the migration of the affinity-labeled receptor resulting in forms of apparent lower molecular mass (as low as 78 kDa). This altered migration, not seen with most other cytosolic proteins, is consistent with the formation of intramolecular disulfide bonds within the receptor which presumably cause it to assume a folded conformation and migrate faster through the gel. At higher concentrations of these reagents (up to 5.0 mM), we also detect a saturably labeled [3H]DM band which has a higher molecular mass (approximately 140 kDa), indicating the formation of intermolecular disulfide bonds between the [3H]DM-labeled receptor and another closely associated protein(s) having a molecular mass of approximately 40 kDa. The effects which these oxidizing reagents have on glucocorticoid receptor structure are completely reversed upon the addition of dithiothreitol, indicating that the observed changes in migration do not reflect receptor proteolysis but rather a folding and unfolding within the receptor monomeric protein. We have also analyzed the effect of this oxidation/reduction on the function of the glucocorticoid receptor. Oxidation of the [3H]DM-labeled receptor complex with 0.5 mM sodium tetrathionate inhibited activation of receptor to a form capable of binding to DNA-cellulose. This inhibition can be reversed with dithiothreitol at 25 degrees C but not at 0 degrees C, suggesting that these oxidizing reagents are inhibitory at the transformation and/or activation steps.(ABSTRACT TRUNCATED AT 400 WORDS)     

Statins and Antimicrobial Effects: Simvastatin as a Potential Drug against Staphylococcus aureus Biofilm

Statins are important lipid-lowering agents with other pleiotropic effects. Several studies have explored a possible protective effect of statins to reduce the morbidity and mortality of many infectious diseases. Staphylococcus aureus is one of the main pathogens implicated in nosocomial infections; its ability to form biofilms makes treatment difficult. The present study observed the MIC of atorvastatin, pravastatin and simvastatin against S. aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis. Simvastatin was the only agent with activity against clinical isolates and reference strains of methicilin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). Thus, the effects of simvastatin on the growth, viability and biofilm formation of S. aureus were tested. In addition, a possible synergistic effect between simvastatin and vancomycin was evaluated. Simvastatin’s MIC was 15.65 µg/mL for S. aureus 29213 and 31.25 µg/mL for the other strains of S. aureus. The effect of simvastatin was bactericidal at 4xMIC and bacteriostatic at the MIC concentration. No synergistic effect was found between simvastatin and vancomycin. However, the results obtained against S. aureus biofilms showed that, in addition to inhibiting adhesion and biofilm formation at concentrations from 1/16xMIC to 4xMIC, simvastatin was also able to act against mature biofilms, reducing cell viability and extra-polysaccharide production. In conclusion, simvastatin showed pronounced antimicrobial activity against S. aureus biofilms, reducing their formation and viability.     

Exploring the Factor Structure of Neurocognitive Measures in Older Individuals

Here we focus on factor analysis from a best practices point of view, by investigating the factor structure of neuropsychological tests and using the results obtained to illustrate on choosing a reasonable solution. The sample (n=1051 individuals) was randomly divided into two groups: one for exploratory factor analysis (EFA) and principal component analysis (PCA), to investigate the number of factors underlying the neurocognitive variables; the second to test the “best fit” model via confirmatory factor analysis (CFA). For the exploratory step, three extraction (maximum likelihood, principal axis factoring and principal components) and two rotation (orthogonal and oblique) methods were used. The analysis methodology allowed exploring how different cognitive/psychological tests correlated/discriminated between dimensions, indicating that to capture latent structures in similar sample sizes and measures, with approximately normal data distribution, reflective models with oblimin rotation might prove the most adequate.     

Leukocyte Inclusion within a Platelet Rich Plasma-Derived Fibrin Scaffold Stimulates a More Pro-Inflammatory Environment and Alters Fibrin Properties

One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFĸB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions.     

Physiographic and climatic events in the Chihuahuan Desert lead to the speciation and distinct demographic patterns of two sister Sceloporus lizards

The biogeographic history of the Chihuahuan Desert is known to be complex, and there is evidence of the effects of physiographic and climatic events in species diversification and demographic population changes in many taxa. Here, using DNA sequence data, we studied the influence of the physiographic and climatic events that occurred in the Chihuahuan Desert during the Pliocene–Pleistocene transition on the speciation and evolutionary history of the sister lizard species Sceloporus cyanostictus and S. gadsdeni. First, based on mtDNA and nDNA sequences, we estimated the divergence times of the sister species. Then, based on mtDNA sequences, we investigated the demographic history of both species within a phylogeographic framework. The divergence time was inferred to be 1.48 Mya, date that corresponds to the existence of a large lake in the Mapimian subprovince, between the current geographic locations of S. cyanostictus and S. gadsdeni. This lake could have acted as a barrier, leading to the speciation of both species. For the demographic history of the two species, we identified two distinct patterns: the population expansion of S. gadsdeni within the Last Glacial Maximum and the potential population decline of S. cyanostictus. Our results can be used as a guide for the study of other aspects that could be critical to developing conservation actions that ensure the survival of not only S. gadsdeni and S. cyanostictus, but also other co‐occurring lizard species.