1000 resultados para COMPARATIVE PHARMACOKINETICS


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In specific and obligate interactions the nature and abundance of a given species can have important effects on the survival and population dynamics of associated organisms. In a phylogeographic framework, we therefore expect that the fates of organisms interacting specifically are also tightly interrelated. Here we investigate such a scenario by analyzing the genetic structures of species interacting in an obligate plant-insect pollination lure-and-trap antagonism, involving Arum maculatum (Araceae) and its specific psychodid (Diptera) visitors Psychoda phalaenoides and Psycha grisescens. Because the interaction is asymmetric (i.e., only the plant depends on the insect), we expect the genetic structure of the plant to be related with the historical pollinator availability, yielding incongruent phylogeographic patterns between the interacting organisms.Using insect mtDNA sequences and plant AFLP genome fingerprinting, we inferred the large-scale phylogeographies of each species and the distribution of genetic diversities throughout the sampled range, and evaluated the congruence in their respective genetic structures using hierarchical analyses of molecular variances (AMOVA). Because the composition of pollinator species varies in Europe, we also examined its association with the spatial genetic structure of the plant.Our findings indicate that while the plant presents a spatially well-defined genetic structure, this is not the case in the insects. Patterns of genetic diversities also show dissimilar distributions among the three interacting species. Phylogeographic histories of the plant and its pollinating insects are thus not congruent, a result that would indicate that plant and insect lineages do not share the same glacial and postglacial histories. However, the genetic structure of the plant can, at least partially, be explained by the type of pollinators available at a regional scale. Differences in life-history traits of available pollinators might therefore have influenced the genetic structure of the plant, the dependent organism, in this antagonistic interaction.

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Pseudomonas knackmussii B13 was the first strain to be isolated in 1974 that could degrade chlorinated aromatic hydrocarbons. This discovery was the prologue for subsequent characterization of numerous bacterial metabolic pathways, for genetic and biochemical studies, and which spurred ideas for pollutant bioremediation. In this study, we determined the complete genome sequence of B13 using next generation sequencing technologies and optical mapping. Genome annotation indicated that B13 has a variety of metabolic pathways for degrading monoaromatic hydrocarbons including chlorobenzoate, aminophenol, anthranilate and hydroxyquinol, but not polyaromatic compounds. Comparative genome analysis revealed that B13 is closest to Pseudomonas denitrificans and Pseudomonas aeruginosa. The B13 genome contains at least eight genomic islands [prophages and integrative conjugative elements (ICEs)], which were absent in closely related pseudomonads. We confirm that two ICEs are identical copies of the 103 kb self-transmissible element ICEclc that carries the genes for chlorocatechol metabolism. Comparison of ICEclc showed that it is composed of a variable and a 'core' region, which is very conserved among proteobacterial genomes, suggesting a widely distributed family of so far uncharacterized ICE. Resequencing of two spontaneous B13 mutants revealed a number of single nucleotide substitutions, as well as excision of a large 220 kb region and a prophage that drastically change the host metabolic capacity and survivability.

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This analysis examined data from a variety of sources to estimate the benefit of enhancing Iowa’s current law to require all passengers to use seat belts. In addition to assessing Iowans’ opinions about changing the law, a literature review, a legislative policy review, and analysis of Iowa crash data were completed. Currently 28 states enforce seat belt laws for all passengers. Belted passengers riding with an unbelted passenger are 2 to 5 times more likely to suffer fatal injuries in a crash relative to when all occupants are using seat belts. Iowans are highly compliant (90%-94%) with the current seat belt law for front seat occupants. Of more than 1000 Iowans surveyed, 85% said they always use a seat belt when riding in the front seat, but only 36% always do so when they ride in the back seat. The most common reasons given for not using seat belts in the back seat are forgetting to buckle up and because it is not the law. Iowans widely support strengthening Iowa’s seat belt law — 62% said Iowa law should require all rear seat passengers to use seat belts. Four out of five respondents said they would use seat belts more often when sitting in the rear seat if it was the law. It is estimated rear seat fatalities would decrease about 48%, from 13 to 7 fatalities annually, if an all-passenger law was implemented in Iowa.

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La survie actuelle après correction chirurgicale de la Tétralogie de Fallot (TDF) est de 97% à 12 ans. Les principaux risques à long terme sont une régurgitation pulmonaire ou une sténose récidivante de la sortie droite du coeur, une tachycardie ventriculaire pouvant entrainer une mort subite. Le but de cette étude rétrospective est de comparer la correction chirurgicale de la TDF avec patch pulmonaire versus un conduit valvé xénogreffe. Le collectif se compose de 127 patients entre 2 mois et 16 ans, opérés pour une TDF entre l'année 2000 et 2010. La correction chirurgicale était soit avec un patch, soit avec un conduit valvé à la sortie droite. Cette étude montre d'une part qu'il n'y a pas de différence de survie à un mois entre les deux méthodes opératoires. De plus, elle montre que, lors de la pose d'un patch, il y a plus de sept fois plus d'insuffisances valvulaires modérées à sévères après un mois que lors de la pose d'un conduit valvé. D'autre part, elle démontre que la différence de gradient résiduel à la sortie droite entre la correction avec patch ou conduit n'est pas significative et que la valeur du gradient résiduel à la sortie droite en postopératoire n'est pas représentative du gradient résiduel à un mois. De plus, cette étude prouve que les coronaires aberrantes ainsi qu'un shunt palliatif de Blalock-Taussig sont des facteurs de risque indépendants pour une correction avec un conduit valvé.

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(241)Pu was determined in slurry samples from a nuclear reactor decommissioning project at the Paul Scherrer Institute (Switzerland). To validate the results, the (241)Pu activities of five samples were determined by LSC (TriCarb and Quantulus) and ICP-MS, with each instrument at a different laboratory. In lack of certified reference materials for (241)Pu, the methods were further validated using the (241)Pu information values of two reference sediments (IAEA-300 and IAEA-384). Excellent agreement with the results was found between LSC and ICP-MS in the nuclear waste slurries and the reference sediments.

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Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male SpragueDawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokineticpharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.

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BACKGROUND: An ADME (absorption, distribution, metabolism and excretion)-pharmacogenetics association study may identify functional variants relevant to the pharmacokinetics of lopinavir co-formulated with ritonavir (LPV/r), a first-line anti-HIV agent. METHODS: An extensive search of literature and web resources helped select ADME genes and single nucleotide polymorphisms (SNPs, functional and HapMap tagging SNPs) with a proven or potentially relevant role in LPV/r pharmacokinetics. The study followed a two-stage design. Stage 1 (discovery) considered a Caucasian population (n=638) receiving LPV/r, where we selected 117 individuals with low LPV clearance (cases) and 90 individuals with high clearance (controls). Genotyping was performed by a 1536-SNP customized GoldenGate Illumina BeadArray. Stage 2 (confirmation) represented a replication study of candidate SNPs from the stage 1 in 148 individuals receiving LPV/r. The analysis led to formal population pharmacokinetic-pharmacogenetic modeling of demographic, environmental and candidate SNP effects. RESULTS: One thousand three hundred and eighty SNPs were successfully genotyped. Nine SNPs prioritized by the stage 1 analysis were brought to replication. Stage 2 confirmed the contribution of two functional SNPs in SLCO1B1, one functional SNP in ABCC2 and a tag SNP of the CYP3A locus in addition to body weight effect and ritonavir coadministration. According to the population pharmacokinetic-pharmacogenetic model, genetic variants explained 5% of LPV variability. Individuals homozygous rs11045819 (SLCO1B1*4) had a clearance of 12.6 l/h, compared with 5.4 l/h in the reference group, and 3.9 l/h in individuals with two or more variant alleles of rs4149056 (SLCO1B1*5), rs717620 (ABCC2) or rs6945984 (CYP3A). A subanalysis confirmed that although a significant part of the variance in LPV clearance was attributed to fluctuation in ritonavir levels, genetic variants had an additional effect on LPV clearance. CONCLUSION: The two-stage strategy successfully identified genetic variants affecting LPV/r pharmacokinetics. Such a general approach of ADME pharmacogenetics should be generalized to other drugs.

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Comparative analyses of spatial genetic structure of populations of plants and the insects they interact with provide an indication of how gene flow, natural selection and genetic drift may jointly influence the distribution of genetic variation and potential for local co-adaptation for interacting species. Here, we analysed the spatial scale of genetic structure within and among nine populations of an interacting species pair, the white campion Silene latifolia and the moth Hadena bicruris, along a latitudinal gradient across Northern/Central Europe. This dioecious, short-lived perennial plant inhabits patchy, often disturbed environments. The moth H. bicruris acts both as its pollinator and specialist seed predator that reproduces by laying eggs in S. latifolia flowers. We used nine microsatellite markers for S. latifolia and eight newly developed markers for H. bicruris. We found high levels of inbreeding in most populations of both plant and pollinator/seed predator. Among populations, significant genetic structure was observed for S. latifolia but not for its pollinator/seed predator, suggesting that despite migration among populations of H. bicruris, pollen is not, or only rarely, carried over between populations, thus maintaining genetic structure among plant populations. There was a weak positive correlation between genetic distances of S. latifolia and H. bicruris. These results indicate that while significant structure of S. latifolia populations creates the potential for differentiation at traits relevant for the interaction with the pollinator/seed predator, substantial gene flow in H. bicruris may counteract this process in at least some populations.

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The objective of this work was to compare biological aspects and life table parameters of the coccinellids Harmonia axyridis, Cycloneda sanguineaand Hippodamia convergens. Insects were fed eggs of Anagasta kuehniella, and reared at 24.5±1ºC, 70±10% relative humidity, with a 12 hour photophase. Hippodamia convergenstook about 1.6 day to complete development, longer than H. axyridis, and 2.4 day longer than C. sanguinea.At immature stages, H. axyridisexhibited the highest survival percentage (49.2%), in comparison to the other coccinellids. For mean adult longevity, H. convergenswas deficient, in comparison with the other species. Mean period of pre oviposition was the longest in C. sanguinea; the longest oviposition time occurred for H. axyridis; and the post oviposition period was similar between the coccinellids. Considering the reproductive parameters, H. axyridisshowed the best performance in all aspects. For life table, the values of H. convergenswere higher than, although close, to those of H. axyridis. Nevertheless, the high net reproductive rate of H. axyridis showed this species potential to increase population size. The biological characteristics of the exotic H. axyridis favors its invasion and establishment in Brazil, corroborating results noticed in other countries.

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Answering patients' evolving, more complex needs has been recognized as a main incentive for the development of interprofessional care. Thus, it is not surprising that patient-centered practice (PCP) has been adopted as a major outcome for interprofessional education. Nevertheless, little research has focused on how PCP is perceived across the professions. This study aimed to address this issue by adopting a phenomenological approach and interviewing three groups of professionals: social workers (n = 10), nurses (n = 10) and physicians (n = 8). All the participants worked in the same department (the General Internal Medicine department of a university affiliated hospital). Although the participants agreed on a core meaning of PCP as identifying, understanding and answering patients' needs, they used many dimensions to define PCP. Overall, the participants expressed value for PCP as a philosophy of care, but there was the sense of a hierarchy of patient-centeredness across the professions, in which both social work and nursing regarded themselves as more patient-centered than others. On their side, physicians seemed inclined to accept their lower position in this hierarchy. Gieryn's concept of boundary work is employed to help illuminate the nature of PCP within an interprofessional context.

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BACKGROUND: Modern sequencing technologies have massively increased the amount of data available for comparative genomics. Whole-transcriptome shotgun sequencing (RNA-seq) provides a powerful basis for comparative studies. In particular, this approach holds great promise for emerging model species in fields such as evolutionary developmental biology (evo-devo). RESULTS: We have sequenced early embryonic transcriptomes of two non-drosophilid dipteran species: the moth midge Clogmia albipunctata, and the scuttle fly Megaselia abdita. Our analysis includes a third, published, transcriptome for the hoverfly Episyrphus balteatus. These emerging models for comparative developmental studies close an important phylogenetic gap between Drosophila melanogaster and other insect model systems. In this paper, we provide a comparative analysis of early embryonic transcriptomes across species, and use our data for a phylogenomic re-evaluation of dipteran phylogenetic relationships. CONCLUSIONS: We show how comparative transcriptomics can be used to create useful resources for evo-devo, and to investigate phylogenetic relationships. Our results demonstrate that de novo assembly of short (Illumina) reads yields high-quality, high-coverage transcriptomic data sets. We use these data to investigate deep dipteran phylogenetic relationships. Our results, based on a concatenation of 160 orthologous genes, provide support for the traditional view of Clogmia being the sister group of Brachycera (Megaselia, Episyrphus, Drosophila), rather than that of Culicomorpha (which includes mosquitoes and blackflies).

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BACKGROUND: Candida glabrata follows C. albicans as the second or third most prevalent cause of candidemia worldwide. These two pathogenic yeasts are distantly related, C. glabrata being part of the Nakaseomyces, a group more closely related to Saccharomyces cerevisiae. Although C. glabrata was thought to be the only pathogenic Nakaseomyces, two new pathogens have recently been described within this group: C. nivariensis and C. bracarensis. To gain insight into the genomic changes underlying the emergence of virulence, we sequenced the genomes of these two, and three other non-pathogenic Nakaseomyces, and compared them to other sequenced yeasts. RESULTS: Our results indicate that the two new pathogens are more closely related to the non-pathogenic N. delphensis than to C. glabrata. We uncover duplications and accelerated evolution that specifically affected genes in the lineage preceding the group containing N. delphensis and the three pathogens, which may provide clues to the higher propensity of this group to infect humans. Finally, the number of Epa-like adhesins is specifically enriched in the pathogens, particularly in C. glabrata. CONCLUSIONS: Remarkably, some features thought to be the result of adaptation of C. glabrata to a pathogenic lifestyle, are present throughout the Nakaseomyces, indicating these are rather ancient adaptations to other environments. Phylogeny suggests that human pathogenesis evolved several times, independently within the clade. The expansion of the EPA gene family in pathogens establishes an evolutionary link between adhesion and virulence phenotypes. Our analyses thus shed light onto the relationships between virulence and the recent genomic changes that occurred within the Nakaseomyces.

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BACKGROUND: Elucidating disease and developmental dysfunction requires understanding variation in phenotype. Single-species model organism anatomy ontologies (ssAOs) have been established to represent this variation. Multi-species anatomy ontologies (msAOs; vertebrate skeletal, vertebrate homologous, teleost, amphibian AOs) have been developed to represent 'natural' phenotypic variation across species. Our aim has been to integrate ssAOs and msAOs for various purposes, including establishing links between phenotypic variation and candidate genes. RESULTS: Previously, msAOs contained a mixture of unique and overlapping content. This hampered integration and coordination due to the need to maintain cross-references or inter-ontology equivalence axioms to the ssAOs, or to perform large-scale obsolescence and modular import. Here we present the unification of anatomy ontologies into Uberon, a single ontology resource that enables interoperability among disparate data and research groups. As a consequence, independent development of TAO, VSAO, AAO, and vHOG has been discontinued. CONCLUSIONS: The newly broadened Uberon ontology is a unified cross-taxon resource for metazoans (animals) that has been substantially expanded to include a broad diversity of vertebrate anatomical structures, permitting reasoning across anatomical variation in extinct and extant taxa. Uberon is a core resource that supports single- and cross-species queries for candidate genes using annotations for phenotypes from the systematics, biodiversity, medical, and model organism communities, while also providing entities for logical definitions in the Cell and Gene Ontologies. THE ONTOLOGY RELEASE FILES ASSOCIATED WITH THE ONTOLOGY MERGE DESCRIBED IN THIS MANUSCRIPT ARE AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/2013-02-21/ CURRENT ONTOLOGY RELEASE FILES ARE AVAILABLE ALWAYS AVAILABLE AT: http://purl.obolibrary.org/obo/uberon/releases/