Dissecting direct and indirect genetic effects on chronic obstructive pulmonary disease (COPD) susceptibility

Cigarette smoking is the major environmental risk factor for chronic obstructive pulmonary disease (COPD). Genome-wide association studies have provided compelling associations for three loci with COPD. In this study, we aimed to estimate direct, i.e., independent from smoking, and indirect effects of those loci on COPD development using mediation analysis. We included a total of 3,424 COPD cases and 1,872 unaffected controls with data on two smoking-related phenotypes: lifetime average smoking intensity and cumulative exposure to tobacco smoke (pack years). Our analysis revealed that effects of two linked variants (rs1051730 and rs8034191) in the AGPHD1/CHRNA3 cluster on COPD development are significantly, yet not entirely, mediated by the smoking-related phenotypes. Approximately 30 % of the total effect of variants in the AGPHD1/CHRNA3 cluster on COPD development was mediated by pack years. Simultaneous analysis of modestly (r ² = 0.21) linked markers in CHRNA3 and IREB2 revealed that an even larger (~42 %) proportion of the total effect of the CHRNA3 locus on COPD was mediated by pack years after adjustment for an IREB2 single nucleotide polymorphism. This study confirms the existence of direct effects of the AGPHD1/CHRNA3, IREB2, FAM13A and HHIP loci on COPD development. While the association of the AGPHD1/CHRNA3 locus with COPD is significantly mediated by smoking-related phenotypes, IREB2 appears to affect COPD independently of smoking.     

Antimicrobial effects of terpinen-4-ol against oral pathogens and its capacity for the modulation of gene expression

Abstract

This study evaluated the antibacterial activity of terpinen-4-ol against Streptococcus mutans and Lactobacillus acidophilus and its influence on gbpA (S. mutans) and slpA (L. acidophilus) gene expression. As measured by XTT assay, the concentrations of terpinen-4-ol that effectively inhibited the biofilm were 0.24% and 0.95% for S. mutans and L. acidophilus, respectively. Confocal microscopy revealed the presence of a biofilm attached to the enamel and dentin block surfaces with significant terpinen-4-ol effects against these microorganisms. The expression of the gbpA and slpA genes involved in adherence and biofilm formation was investigated using RT-PCR. Expression of these genes decreased after 15?min with 0.24% and 0.95% terpinen-4-ol in S. mutans and L. acidophilus, respectively. These findings demonstrate the antimicrobial activity of terpinen-4-ol and its ability to modulate the expression of gbpA and slpA genes, emphasizing the therapeutic capacity of terpinen-4-ol as an alternative to inhibit adherence in biofilm.     

About Bullockia gen. nov., Trichomycterus mendozensis n. sp. and revision of the family Trichomycteridae (Pisces,Siluriformes)

A new genus of the family Trichomycteridae, Bullockia, and a new species of Trichomycterus are described. Bullockia gen. nov. is a monospecific and relict genus in the freshwaters of Chile. Trichomycterus mendozensis n. sp. is a freshwater relict from Argentina. Preliminary diagnoses of the subfamilies Pygidiinae and Nematogenyinae and the genera Trichomycterus, Hatcheria and Nematogenys are given.     

The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.     

Serologic survey of West Nile virus in horses from Central-West,Northeast and Southeast Brazil

Since the emergence of West Nile virus (WNV) in North America in 1999, there have been several reports of WNV activity in Central and South American countries. To detect WNV in Brazil, we performed a serological survey of horses from different regions of Brazil using recombinant peptides from domain III of WNV. Positive samples were validated with the neutralisation test. Our results showed that of 79 ELISA-positive horses, nine expressed WNV-specific neutralising antibodies. Eight of the infected horses were from the state of Mato Grosso do Sul and one was from the state of Paraíba. Our results provide additional evidence for the emergence of WNV in Brazil and for its circulation in multiple regions of the country.     

Vocalizations and morphology: interpreting the divergence among populations of Chough Pyrrhocorax pyrrhocorax and Alpine Chough P. graculus

Capsule Differences in vocalizations among populations are mostly explained on morphological bases, but historical factors may have played a significant role in differentiation processes.

Aims To investigate the relationships among vocal and morphological variation in two corvids: Chough and Alpine Chough.

Methods We used data from 11 populations of Chough and seven populations of Alpine Chough spanning the Palearctic distribution of the two species. Three data sets (morphometry, spectrotemporal parameters of trill calls and acoustic repertoire) were analysed and their variation compared with uni- and multivariate techniques.

Results In both species, morphological differences among populations were correlated to spectro-temporal variation of trills; in particular, frequencies of calls were negatively correlated to wing length (an indicator of body size). By considering only co-existing populations of the two species, the magnitude of morphological and spectrotemporal divergence was similar.

Conclusions In both species, birds from populations with similar morphology uttered similar call types and trills with close spectrotemporal features. In particular, larger-sized populations, as expressed by wing length, emitted lower pitched calls. However, the fact that dissimilarities in repertoire and morphology were correlated cannot be explained only by appealing to functional explanations, as the observed intraspecific morphological variability does not seem to be high enough to promote consistent changes in the pool of calls. In this case, historical factors might have contributed to the present pattern of differentiation.     

Effects of cytoprotective antioxidants on lymphocytes from representative mitochondrial neurodegenerative diseases

Two new aza analogues of the neuroprotective agent idebenone have been synthesized and characterized. Their antioxidant activity, and ability to augment ATP levels have been evaluated in several different cell lines having suboptimal mitochondrial function. Both compounds were found to be good ROS scavengers, and to protect the cells from oxidative stress induced by glutathione depletion. The compounds were more effective than idebenone in neurodegenerative disease cells. These novel pyrimidinol derivatives were also shown to augment ATP levels in coenzyme Q₁₀-deficient human lymphocytes. The more lipophilic side chains attached to the pyrimidinol redox core in these compounds resulted in less inhibition of the electron transport chain and improved antioxidant activity.     

Nucleic acid changes during photodynamic inactivation of bacteria by cationic porphyrins

Light activation of photosensitizing dyes in presence of molecular oxygen generates highly cytotoxic reactive oxygen species leading to cell inactivation. Nucleic acids are molecular targets of this photodynamic action but not considered the main cause of cell death. The in vivo effect of the photodynamic process on the intracellular nucleic acid content of Escherichia coli and Staphylococcus warneri was evaluated herein.Two cationic porphyrins (Tetra-Py⁺-Me and Tri-Py⁺-Me-PF) were used to photoinactivate E. coli (5.0 μM; 10⁸ cells mL^?1) and S. warneri (0.5 μM; 10⁸ cells mL^?1) upon white light irradiation at 4.0 mW cm^?2 for 270 min and 40 min, respectively. Total nucleic acids were extracted from photosensitized bacteria after different times of irradiation and analyzed by agarose gel electrophoresis. The double-stranded DNA was quantified by fluorimetry and the porphyrin binding to bacteria was determined by spectrofluorimetry.E. coli was completely photoinactivated with both porphyrins (5.0 μM), whereas S. warneri was only completely inactivated by Tri-Py⁺-Me-PF (0.5 μM). The hierarchy of nucleic acid changes in E. coli was in the order: 23S rRNA > 16S rRNA > genomic DNA. The nucleic acids of S. warneri were extensively reduced after 5 min with Tri-Py⁺-Me-PF but almost unchanged with Tetra-Py⁺-Me after 40 min of irradiation. The amount of Tri-Py⁺-Me-PF bound to E. coli after washing the cells is higher than Tetra-Py⁺-Me and the opposite was observed for S. warneri. The binding capacity of the photosensitizers is not directly related to the PDI efficiency or nucleic acid reduction and this reduction occurs in parallel with the decrease of surviving cells.     

Seasonal variation in leaf traits between congeneric savanna and forest trees in Central Brazil: implications for forest expansion into savanna

The ecology of forest and savanna trees species will largely determine the structure and dynamics of the forest–savanna boundaries, but little is known about the constraints to leaf trait variation imposed by selective forces and evolutionary history during the process of savanna invasion by forest species. We compared seasonal patterns in leaf traits related to leaf structure, carbon assimilation, water, and nutrient relations in 10 congeneric species pairs, each containing one savanna species and one forest species. All individuals were growing in dystrophic oxisols in a fire-protected savanna of Central Brazil. We tested the hypothesis that forest species would be more constrained by seasonal drought and nutrient-poor soils than their savanna congeners. We also hypothesized that habitat, rather than phylogeny, would explain more of the interspecific variance in leaf traits of the studied species. We found that throughout the year forest trees had higher specific leaf area (SLA) but lower integrated water use efficiency than savanna trees. Forest and savanna species maintained similar values of predawn and midday leaf water potential along the year. Lower values were measured in the dry season. However, this was achieved by a stronger regulation of stomatal conductance and of CO₂ assimilation on an area basis (A _area) in forest trees, particularly toward the end of the dry season. Relative to savanna trees, forest trees maintained similar (P, K, Ca, and Mg) or slightly higher (N) leaf nutrient concentrations. For the majority of traits, more variance was explained by phylogeny, than by habitat of origin, with the exception of SLA, leaf N concentration, and A _area, which were apparently subjected to different selective pressures in the savanna and forest environments. In conclusion, water shortage during extended droughts would be more limiting for forest trees than nutrient-poor soils.