CYP2C19 and ABCB1 gene polymorphisms are differently distributed according to ethnicity in the Brazilian general population

<p>Abstract</p> <p>Background</p> <p>Recent studies have reported the clinical importance of <it>CYP2C19 </it>and <it>ABCB1 </it>polymorphisms in an individualized approach to clopidogrel treatment. The aims of this study were to evaluate the frequencies of <it>CYP2C19 </it>and <it>ABCB1 </it>polymorphisms and to identify the clopidogrel-predicted metabolic phenotypes according to ethnic groups in a sample of individuals representative of a highly admixtured population.</p> <p>Methods</p> <p>One hundred and eighty-three Amerindians and 1,029 subjects of the general population of 4 regions of the country were included. Genotypes for the <it>ABCB1</it>c.C3435T (rs1045642), <it>CYP2C19*2 </it>(rs4244285), <it>CYP2C19*3 </it>(rs4986893), <it>CYP2C19*4 </it>(rs28399504), <it>CYP2C19*5 </it>(rs56337013), and <it>CYP2C19*17 </it>(rs12248560) polymorphisms were detected by polymerase chain reaction followed by high resolution melting analysis. The <it>CYP2C19*3</it>, <it>CYP2C19*4 </it>and <it>CYP2C19*5 </it>variants were genotyped in a subsample of subjects (300 samples randomly selected).</p> <p>Results</p> <p>The <it>CYP2C19*3 </it>and <it>CYP2C19*5 </it>variant alleles were not detected and the <it>CYP2C19*4 </it>variant allele presented a frequency of 0.3%. The allelic frequencies for the <it>ABCB1</it>c.C3435T, <it>CYP2C19*2 </it>and <it>CYP2C19*17 </it>polymorphisms were differently distributed according to ethnicity: Amerindian (51.4%, 10.4%, 15.8%); Caucasian descent (43.2%, 16.9%, 18.0%); Mulatto (35.9%, 16.5%, 21.3%); and African descent (32.8%, 20.2%, 26.3%) individuals, respectively. As a result, self-referred ethnicity was able to predict significantly different clopidogrel-predicted metabolic phenotypes prevalence even for a highly admixtured population.</p> <p>Conclusion</p> <p>Our findings indicate the existence of inter-ethnic differences in the <it>ABCB1 </it>and <it>CYP2C19 </it>variant allele frequencies in the Brazilian general population plus Amerindians. This information could help in stratifying individuals from this population regarding clopidogrel-predicted metabolic phenotypes and design more cost-effective programs towards individualization of clopidogrel therapy.</p

Diversity of Bacteria Associated with Bursaphelenchus xylophilus and Other Nematodes Isolated from Pinus pinaster Trees with Pine Wilt Disease

The pinewood nematode (PWN), Bursaphelenchus xylophilus, has been thought to be the only causal agent of pine wilt disease (PWD), however, since bacteria have been suggested to play a role in PWD, it is important to know the diversity of the microbial community associated to it. This study aimed to assess the microbial community associated with B. xylophilus and with other nematodes isolated from pine trees, Pinus pinaster, with PWD from three different affected forest areas in Portugal. One hundred and twenty three bacteria strains were isolated from PWN and other nematodes collected from 14 P. pinaster. The bacteria strains were identified by comparative analysis of the 16S rRNA gene partial sequence. All except one Gram-positive strain (Actinobacteria) belonged to the Gram-negative Beta and Gammaproteobacteria. Most isolates belonged to the genus Pseudomonas, Burkholderia and to the family Enterobacteriaceae. Species isolated in higher percentage were Pseudomonas lutea, Yersinia intermedia and Burkholderia tuberum. The major bacterial population associated to the nematodes differed according to the forest area and none of the isolated bacterial species was found in all different forest areas. For each of the sampled areas, 60 to 100% of the isolates produced siderophores and at least 40% produced lipases. The ability to produce siderophores and lipases by most isolates enables these bacteria to have a role in plant physiological response. This research showed a high diversity of the microbial community associated with B. xylophilus and other nematodes isolated from P. pinaster with PWD

Nematicidal Bacteria Associated to Pinewood Nematode Produce Extracellular Proteases

Bacteria associated with the nematode Bursaphelenchus xylophilus, a pathogen of trees and the causal agent of pine wilt disease (PWD) may play a role in the disease. In order to evaluate their role (positive or negative to the tree), strains isolated from the track of nematodes from infected Pinus pinaster trees were screened, in vitro, for their nematicidal potential. The bacterial products, from strains more active in killing nematodes, were screened in order to identify and characterize the nematicidal agent. Forty-seven strains were tested and, of these, 21 strains showed capacity to produce extracellular products with nematicidal activity. All Burkholderia strains were non-toxic. In contrast, all Serratia strains except one exhibited high toxicity. Nematodes incubated with Serratia strains showed, by SEM observation, deposits of bacteria on the nematode cuticle. The most nematicidal strain, Serratia sp. A88copa13, produced proteases in the supernatant. The use of selective inhibitors revealed that a serine protease with 70 kDa was majorly responsible for the toxicity of the supernatant. This extracellular serine protease is different phylogenetically, in size and biochemically from previously described proteases. Nematicidal assays revealed differences in nematicidal activity of the proteases to different species of Bursaphelenchus, suggesting its usefulness in a primary screen of the nematodes. This study offers the basis for further investigation of PWD and brings new insights on the role bacteria play in the defense of pine trees against B. xylophilus. Understanding all the factors involved is important in order to develop strategies to control B. xylophilus dispersion.This research was partially supported by Direcção Regional de Florestas, Fundo Florestal Permanente and Autoridade Florestal Nacional, through a national project ‘O nemátode-da-madeira-do-pinheiro (NMP), Bursaphelenchus xylophilus’ and by FEDER funds through the Programa Operacional Factores de Competitividade – COMPETE and by national funds through the Fundação para a Ciência e Tecnologia (FCT), Portugal, under the project PTDC/AGR-CFL/115373/2009. D.N.P. was supported by FCT, Portugal, graduate fellowship SFRH/BD/61311/2009. G.P. was supported by FCT, Portugal, fellowship PTDC/AGR-CFL/115373/2009

Search for a correlation between the UHECRs measured by the Pierre Auger Observatory and the Telescope Array and the neutrino candidate events from IceCube

We have conducted three searches for correlations between ultra-high energy cosmic rays detected by the Telescope Array and the Pierre Auger Observatory, and high-energy neutrino candidate events from IceCube. Two cross-correlation analyses with UHECRs are done: one with 39 cascades from the IceCube ‘high-energy starting events’ sample and the other with 16 high-energy ‘track events’. The angular separation between the arrival directions of neutrinos and UHECRs is scanned over. The same events are also used in a separate search using a maximum likelihood approach, after the neutrino arrival directions are stacked. To estimate the significance we assume UHECR magnetic deflections to be inversely proportional to their energy, with values 3◦ , 6◦ and 9 ◦ at 100 EeV to allow for the uncertainties on the magnetic field strength and UHECR charge. A similar analysis is performed on stacked UHECR arrival directions and the IceCube sample of through-going muon track events which were optimized for neutrino point-source searches. </p

Search for correlations between the arrival directions of IceCube neutrino events and ultrahigh-energy cosmic rays detected by the Pierre Auger Observatory and the Telescope Array

This paper presents the results of different searches for correlations between very high-energy neutrino candidates detected by IceCube and the highest-energy cosmic rays measured by the Pierre Auger Observatory and the Telescope Array. We first consider samples of cascade neutrino events and of high-energy neutrino-induced muon tracks, which provided evidence for a neutrino flux of astrophysical origin, and study their cross-correlation with the ultrahigh-energy cosmic ray (UHECR) samples as a function of angular separation. We also study their possible directional correlations using a likelihood method stacking the neutrino arrival directions and adopting different assumptions on the size of the UHECR magnetic deflections. Finally, we perform another likelihood analysis stacking the UHECR directions and using a sample of through-going muon tracks optimized for neutrino point-source searches with sub-degree angular resolution. No indications of correlations at discovery level are obtained for any of the searches performed. The smallest of the p-values comes from the search for correlation between UHECRs with IceCube high-energy cascades, a result that should continue to be monitored.ope

Search for a correlation between the UHECRs measured by the Pierre Auger Observatory and the Telescope Array and the neutrino candidate events from IceCube

We have conducted three searches for correlations between ultra-high energy cosmic rays detected by the Telescope Array and the Pierre Auger Observatory, and high-energy neutrino candidate events from IceCube. Two cross-correlation analyses with UHECRs are done: one with 39 cascades from the IceCube ‘high-energy starting events’ sample and the other with 16 high-energy ‘track events’. The angular separation between the arrival directions of neutrinos and UHECRs is scanned over. The same events are also used in a separate search using a maximum likelihood approach, after the neutrino arrival directions are stacked. To estimate the significance we assume UHECR magnetic deflections to be inversely proportional to their energy, with values 3◦ , 6◦ and 9 ◦ at 100 EeV to allow for the uncertainties on the magnetic field strength and UHECR charge. A similar analysis is performed on stacked UHECR arrival directions and the IceCube sample of through-going muon track events which were optimized for neutrino point-source searches. </p

Search for a correlation between the UHECRs measured by the Pierre Auger Observatory and the Telescope Array and the neutrino candidate events from IceCube

We have conducted three searches for correlations between ultra-high energy cosmic rays detected by the Telescope Array and the Pierre Auger Observatory, and high-energy neutrino candidate events from IceCube. Two cross-correlation analyses with UHECRs are done: one with 39 cascades from the IceCube `high-energy starting events' sample and the other with 16 high-energy `track events'. The angular separation between the arrival directions of neutrinos and UHECRs is scanned over. The same events are also used in a separate search using a maximum likelihood approach, after the neutrino arrival directions are stacked. To estimate the significance we assume UHECR magnetic deflections to be inversely proportional to their energy, with values 3◦, 6◦ and 9◦ at 100 EeV to allow for the uncertainties on the magnetic field strength and UHECR charge. A similar analysis is performed on stacked UHECR arrival directions and the IceCube sample of through-going muon track events which were optimized for neutrino point-source searches