The pig is a better model than the rabbit or rat for studying the pathophysiology of human mesenteric arteries.

AIMS: Animal models are essential to investigate cardiovascular pathophysiology and pharmacology, but phylogenetic diversity makes it necessary to identify the model with vasculature most similar to that of humans. METHODS AND RESULTS: In this study, we compared the mesenteric arteries of humans, pigs, rabbits and rats in terms of the i) evolutionary changes in the amino acid sequences of α1 and ß2 adrenoceptors; M1, M2, and M3 muscarinic receptors; and bradykinin (BKR) and thromboxane-prostanoid (TP) receptors, through bioinformatics tools; ii) expression of α1, ß2, M1, M3 and TP receptors in each tunica, as assessed by immunofluorescence; and iii) reactivity to receptor-dependent and independent contractile agonists and relaxants, by performing organ bath assays. Phylogenetically, pigs showed the highest degree of evolutionary closeness to humans for all receptors, and with the exception of BKR, rabbits presented the greatest evolutionary difference compared to humans, pigs and rats. The expression of the measured receptors in the three vascular tunica in pigs was most similar to that in humans. Using a one-way ANOVA to determine the differences in vascular reactivity, we found that the reactivity of pigs was the most similar to that of humans in terms of sensitivity (pD2) and maximum effect of vascular reactivity (Emax) to KCl, phenylephrine, isoproterenol and carbachol. CONCLUSIONS: The pig is a better vascular model than the rabbit or rat to extrapolate results to human mesenteric arteries. Comparative vascular studies have implications for understanding the evolutionary history of different species. TRANSLATIONAL PERSPECTIVE: The presented findings are useful for identifying an animal model with a vasculature that is similar to that of humans. This information is important to extrapolate, with greater precision, the findings in arterial pathophysiology or pharmacology from animal models to the healthy or diseased human being.

Comparative Genomics and Evolutionary Analysis of RNA-Binding Proteins of the CsrA Family in the Genus Pseudomonas.

Gene expression is adjusted according to cellular needs through a combination of mechanisms acting at different layers of the flow of genetic information. At the posttranscriptional level, RNA-binding proteins are key factors controlling the fate of nascent and mature mRNAs. Among them, the members of the CsrA family are small dimeric proteins with heterogeneous distribution across the bacterial tree of life, that act as global regulators of gene expression because they recognize characteristic sequence/structural motifs (short hairpins with GGA triplets in the loop) present in hundreds of mRNAs. The regulatory output of CsrA binding to mRNAs is counteracted in most cases by molecular mimic, non-protein coding RNAs that titrate the CsrA dimers away from the target mRNAs. In γ-proteobacteria, the regulatory modules composed by CsrA homologs and the corresponding antagonistic sRNAs, are mastered by two-component systems of the GacS-GacA type, which control the transcription and the abundance of the sRNAs, thus constituting the rather linear cascade Gac-Rsm that responds to environmental or cellular signals to adjust and coordinate the expression of a set of target genes posttranscriptionally. Within the γ-proteobacteria, the genus Pseudomonas has been shown to contain species with different number of active CsrA (RsmA) homologs and of molecular mimic sRNAs. Here, with the help of the increasing availability of genomic data we provide a comprehensive state-of-the-art picture of the remarkable multiplicity of CsrA lineages, including novel yet uncharacterized paralogues, and discuss evolutionary aspects of the CsrA subfamilies of the genus Pseudomonas, and implications of the striking presence of csrA alleles in natural mobile genetic elements (phages and plasmids).

HyPhy 2.5-A Customizable Platform for Evolutionary Hypothesis Testing Using Phylogenies.

HYpothesis testing using PHYlogenies (HyPhy) is a scriptable, open-source package for fitting a broad range of evolutionary models to multiple sequence alignments, and for conducting subsequent parameter estimation and hypothesis testing, primarily in the maximum likelihood statistical framework. It has become a popular choice for characterizing various aspects of the evolutionary process: natural selection, evolutionary rates, recombination, and coevolution. The 2.5 release (available from www.hyphy.org) includes a completely re-engineered computational core and analysis library that introduces new classes of evolutionary models and statistical tests, delivers substantial performance and stability enhancements, improves usability, streamlines end-to-end analysis workflows, makes it easier to develop custom analyses, and is mostly backward compatible with previous HyPhy releases.

Assessing the effect of abiotic variables and zooplankton on picocyanobacterial dominance in two tropical mesotrophic reservoirs by means of evolutionary computation.

Evolutionary computation has been applied to predict the occurrence of massive cyanobacteria proliferations; in the present study, this tool was further used to explore the factors responsible for maintaining picocyanobacterial dominance. Aiming to increase the understanding of factors that promote dominance of picocyanobacteria in tropical reservoirs, we chose two reservoirs used for water supplies located in different regions of Brazil and subjected to climate changes such as warmer winters that intensify water column stratification and prolonged dry seasons that cause water level decreases. This study focused on the diagnosis of the relationships among picocyanobacteria (1-2 µm), zooplankton and environmental variables using evolutionary computation. The integrated data analysis performed here was very successful in elucidating the dynamics of picocyanobacterial density variation influenced by both abiotic and biotic factors by the modeling approach. Relative water column stability - RWCS and electrical conductivity were highlighted as the most important environmental drivers for picocyanobacterial peaks. Hybrid Evolutionary Analysis (HEA) models for the two reservoirs indicated for the first time in the literature that rotifers, small-sized cladocerans and copepods (mainly nauplii) can directly or indirectly control picocyanobacteria in tropical mesotrophic reservoirs, depending on RWCS conditions and electrical conductivity. However, this control is modulated by pH, water transparency and water temperature thresholds.

Molecular and serological detection of Leishmania spp. in horses from an endemic area for canine visceral leishmaniasis in southeastern Brazil / Detecção molecular e sorológica de infecção por Leishmania (Leishmania) infantum em cavalos na região Sudeste do Brasil

This study aimed to verify the occurrence of Leishmania spp. and Leishmania (Leishmania) infantum in horses from a visceral leishmaniasis endemic area in Brazil. DNA samples from blood and conjunctival swab (CS) were tested by PCR and Indirect Immunofluorescence Antibody Test (IFAT). Although none of the horses was clinically sick, animals infected by Leishmania spp. were found and some could be characterized as infected by L. (L.) infantum. From 40 horses, 100% of the animals were positive by blood PCR, 90% (36/40) by CS PCR, and 2.5% (01/40) in serodiagnosis, by IFAT. Six from these 40 horses were L. (L.) infantum positive by blood PCR. Direct sequencing and analysis of amplicons resulted in a sequence to evolutionary analysis. Results indicate the presence of Leishmania spp. and L. (L.) infantum infecting healthy horses in Brazil. The presence of Leishmania spp. and L. (L.) infantum DNA in asymptomatic horses suggests that they can be important reservoirs of these parasites, a highly relevant finding for the epidemiological surveillance of the diseases they cause.(AU)

O estudo objetivou verificar a ocorrência de Leishmania spp. e Leishmania (Leishmania) infantum em cavalos de uma região endêmica para leishmaniose visceral do Brasil. Amostras de DNA de sangue e suabe conjuntival (SC) foram testadas pela PCR e pela Reação de Imunofluorescência Indireta (RIFI). Embora nenhum cavalo estivesse clinicamente doente, animais infectados por Leishmania spp. e L. (L.) infantum foram encontrados em Ilha Solteira/SP. Dos 40 cavalos, 100% (40/40) foram positivos pela PCR de sangue, 90% (36/40) pela PCR de SC, e 2,5% (01/40) no sorodiagnóstico, pela RIFI. Seis desses 40 cavalos foram positivos para L. (L.) infantum pela PCR de sangue. O sequenciamento direto e a análise dos amplicons resultaram em uma sequência para análise evolutiva. Os resultados indicam a presença de Leishmania spp. e L. (L.) infantum infectando cavalos saudáveis no Brasil. A presença de DNA de Leishmania spp. and L. (L.) infantum em cavalos saudáveis sugere que eles podem ser importantes reservatórios desses parasitas, um achado altamente relevante para a vigilância epidemiológica das doenças que causam.(AU)

Evolution of equine influenza viruses (H3N8) during a Brazilian outbreak, 2015

Equine influenza is one of the major respiratory infectious diseases in horses. An equine influenza virus outbreak was identified in vaccinated and unvaccinated horses in a veterinary school hospital in São Paulo, SP, Brazil, in September 2015. The twelve equine influenza viruses isolated belonged to Florida Clade 1. The hemagglutinin and neuraminidase amino acid sequences were compared with the recent isolates from North and South America and the World Organisation for Animal Health recommended Florida Clade 1 vaccine strain. The hemagglutinin amino acid sequences had nine substitutions, compared with the vaccine strain. Two of them were in antigenic site A (A138S and G142R), one in antigenic site E (R62K) and another not in antigenic site (K304E). The four substitutions changed the hydrophobicity of hemagglutinin. Three distinct genetic variants were identified during the outbreak. Eleven variants were found in four quasispecies, which suggests the equine influenza virus evolved during the outbreak. The use of an out of date vaccine strain or updated vaccines without the production of protective antibody titers might be the major contributing factors on virus dissemination during this outbreak.(AU)

Evolution of equine influenza viruses (H3N8) during a Brazilian outbreak, 2015

Abstract Equine influenza is one of the major respiratory infectious diseases in horses. An equine influenza virus outbreak was identified in vaccinated and unvaccinated horses in a veterinary school hospital in São Paulo, SP, Brazil, in September 2015. The twelve equine influenza viruses isolated belonged to Florida Clade 1. The hemagglutinin and neuraminidase amino acid sequences were compared with the recent isolates from North and South America and the World Organisation for Animal Health recommended Florida Clade 1 vaccine strain. The hemagglutinin amino acid sequences had nine substitutions, compared with the vaccine strain. Two of them were in antigenic site A (A138S and G142R), one in antigenic site E (R62K) and another not in antigenic site (K304E). The four substitutions changed the hydrophobicity of hemagglutinin. Three distinct genetic variants were identified during the outbreak. Eleven variants were found in four quasispecies, which suggests the equine influenza virus evolved during the outbreak. The use of an out of date vaccine strain or updated vaccines without the production of protective antibody titers might be the major contributing factors on virus dissemination during this outbreak.

Molecular and serological detection of Leishmania spp. in horses from an endemic area for canine visceral leishmaniasis in southeastern Brazil / Detecção molecular e sorológica de infecção por Leishmania (Leishmania) infantum em cavalos na região Sudeste do Brasil

This study aimed to verify the occurrence of Leishmania spp. and Leishmania (Leishmania) infantum in horses from a visceral leishmaniasis endemic area in Brazil. DNA samples from blood and conjunctival swab (CS) were tested by PCR and Indirect Immunofluorescence Antibody Test (IFAT). Although none of the horses was clinically sick, animals infected by Leishmania spp. were found and some could be characterized as infected by L. (L.) infantum. From 40 horses, 100% of the animals were positive by blood PCR, 90% (36/40) by CS PCR, and 2.5% (01/40) in serodiagnosis, by IFAT. Six from these 40 horses were L. (L.) infantum positive by blood PCR. Direct sequencing and analysis of amplicons resulted in a sequence to evolutionary analysis. Results indicate the presence of Leishmania spp. and L. (L.) infantum infecting healthy horses in Brazil. The presence of Leishmania spp. and L. (L.) infantum DNA in asymptomatic horses suggests that they can be important reservoirs of these parasites, a highly relevant finding for the epidemiological surveillance of the diseases they cause.(AU)

O estudo objetivou verificar a ocorrência de Leishmania spp. e Leishmania (Leishmania) infantum em cavalos de uma região endêmica para leishmaniose visceral do Brasil. Amostras de DNA de sangue e suabe conjuntival (SC) foram testadas pela PCR e pela Reação de Imunofluorescência Indireta (RIFI). Embora nenhum cavalo estivesse clinicamente doente, animais infectados por Leishmania spp. e L. (L.) infantum foram encontrados em Ilha Solteira/SP. Dos 40 cavalos, 100% (40/40) foram positivos pela PCR de sangue, 90% (36/40) pela PCR de SC, e 2,5% (01/40) no sorodiagnóstico, pela RIFI. Seis desses 40 cavalos foram positivos para L. (L.) infantum pela PCR de sangue. O sequenciamento direto e a análise dos amplicons resultaram em uma sequência para análise evolutiva. Os resultados indicam a presença de Leishmania spp. e L. (L.) infantum infectando cavalos saudáveis no Brasil. A presença de DNA de Leishmania spp. and L. (L.) infantum em cavalos saudáveis sugere que eles podem ser importantes reservatórios desses parasitas, um achado altamente relevante para a vigilância epidemiológica das doenças que causam.(AU)

Evolution of equine influenza viruses (H3N8) during a Brazilian outbreak, 2015.

Equine influenza is one of the major respiratory infectious diseases in horses. An equine influenza virus outbreak was identified in vaccinated and unvaccinated horses in a veterinary school hospital in São Paulo, SP, Brazil, in September 2015. The twelve equine influenza viruses isolated belonged to Florida Clade 1. The hemagglutinin and neuraminidase amino acid sequences were compared with the recent isolates from North and South America and the World Organisation for Animal Health recommended Florida Clade 1 vaccine strain. The hemagglutinin amino acid sequences had nine substitutions, compared with the vaccine strain. Two of them were in antigenic site A (A138S and G142R), one in antigenic site E (R62K) and another not in antigenic site (K304E). The four substitutions changed the hydrophobicity of hemagglutinin. Three distinct genetic variants were identified during the outbreak. Eleven variants were found in four quasispecies, which suggests the equine influenza virus evolved during the outbreak. The use of an out of date vaccine strain or updated vaccines without the production of protective antibody titers might be the major contributing factors on virus dissemination during this outbreak.

Molecular and serological detection of Leishmania spp. in horses from an endemic area for canine visceral leishmaniasis in southeastern Brazil

ABSTRACT: This study aimed to verify the occurrence of Leishmania spp. and Leishmania (Leishmania) infantum in horses from a visceral leishmaniasis endemic area in Brazil. DNA samples from blood and conjunctival swab (CS) were tested by PCR and Indirect Immunofluorescence Antibody Test (IFAT). Although none of the horses was clinically sick, animals infected by Leishmania spp. were found and some could be characterized as infected by L. (L.) infantum. From 40 horses, 100% of the animals were positive by blood PCR, 90% (36/40) by CS PCR, and 2.5% (01/40) in serodiagnosis, by IFAT. Six from these 40 horses were L. (L.) infantum positive by blood PCR. Direct sequencing and analysis of amplicons resulted in a sequence to evolutionary analysis. Results indicate the presence of Leishmania spp. and L. (L.) infantum infecting healthy horses in Brazil. The presence of Leishmania spp. and L. (L.) infantum DNA in asymptomatic horses suggests that they can be important reservoirs of these parasites, a highly relevant finding for the epidemiological surveillance of the diseases they cause.

RESUMO: O estudo objetivou verificar a ocorrência de Leishmania spp. e Leishmania (Leishmania) infantum em cavalos de uma região endêmica para leishmaniose visceral do Brasil. Amostras de DNA de sangue e suabe conjuntival (SC) foram testadas pela PCR e pela Reação de Imunofluorescência Indireta (RIFI). Embora nenhum cavalo estivesse clinicamente doente, animais infectados por Leishmania spp. e L. (L.) infantum foram encontrados em Ilha Solteira/SP. Dos 40 cavalos, 100% (40/40) foram positivos pela PCR de sangue, 90% (36/40) pela PCR de SC, e 2,5% (01/40) no sorodiagnóstico, pela RIFI. Seis desses 40 cavalos foram positivos para L. (L.) infantum pela PCR de sangue. O sequenciamento direto e a análise dos amplicons resultaram em uma sequência para análise evolutiva. Os resultados indicam a presença de Leishmania spp. e L. (L.) infantum infectando cavalos saudáveis no Brasil. A presença de DNA de Leishmania spp. and L. (L.) infantum em cavalos saudáveis sugere que eles podem ser importantes reservatórios desses parasitas, um achado altamente relevante para a vigilância epidemiológica das doenças que causam.

Evolution of equine influenza viruses (H3N8) during a Brazilian outbreak, 2015

Abstract Equine influenza is one of the major respiratory infectious diseases in horses. An equine influenza virus outbreak was identified in vaccinated and unvaccinated horses in a veterinary school hospital in São Paulo, SP, Brazil, in September 2015. The twelve equine influenza viruses isolated belonged to Florida Clade 1. The hemagglutinin and neuraminidase amino acid sequences were compared with the recent isolates from North and South America and the World Organisation for Animal Health recommended Florida Clade 1 vaccine strain. The hemagglutinin amino acid sequences had nine substitutions, compared with the vaccine strain. Two of them were in antigenic site A (A138S and G142R), one in antigenic site E (R62K) and another not in antigenic site (K304E). The four substitutions changed the hydrophobicity of hemagglutinin. Three distinct genetic variants were identified during the outbreak. Eleven variants were found in four quasispecies, which suggests the equine influenza virus evolved during the outbreak. The use of an out of date vaccine strain or updated vaccines without the production of protective antibody titers might be the major contributing factors on virus dissemination during this outbreak.