54 research outputs found

    Evolutionary Repercussions of Avian Culling on Host Resistance and Influenza Virulence

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    Keeping pandemic influenza at bay is a global health priority. Of particular concern is the continued spread of the influenza subtype H5N1 in avian populations and the increasing frequency of transmission to humans. To decrease this threat, mass culling is the principal strategy for eradicating influenza in avian populations. Although culling has a crucial short-term epidemiological benefit, evolutionary repercussions on reservoir hosts and on the viral population have not been considered.To explore the epidemiological and evolutionary repercussions of mass avian culling, we combine population genetics and epidemiological influenza dynamics in a mathematical model parameterized by clinical, epidemiological, and poultry data. We model the virulence level of influenza and the selection on a dominant allele that confers resistance against influenza [1, 2] in a poultry population. Our findings indicate that culling impedes the evolution of avian host resistance against influenza. On the pathogen side of the coevolutionary race between pathogen and host, culling selects for heightened virulence and transmissibility of influenza.Mass culling achieves a short-term benefit at the expense of long-term detriments: a more genetically susceptible host population, ultimately greater mortality, and elevated influenza virulence

    Cdx ParaHox genes acquired distinct developmental roles after gene duplication in vertebrate evolution

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    BACKGROUND: The functional consequences of whole genome duplications in vertebrate evolution are not fully understood. It remains unclear, for instance, why paralogues were retained in some gene families but extensively lost in others. Cdx homeobox genes encode conserved transcription factors controlling posterior development across diverse bilaterians. These genes are part of the ParaHox gene cluster. Multiple Cdx copies were retained after genome duplication, raising questions about how functional divergence, overlap, and redundancy respectively contributed to their retention and evolutionary fate. RESULTS: We examined the degree of regulatory and functional overlap between the three vertebrate Cdx genes using single and triple morpholino knock-down in Xenopus tropicalis followed by RNA-seq. We found that one paralogue, Cdx4, has a much stronger effect on gene expression than the others, including a strong regulatory effect on FGF and Wnt genes. Functional annotation revealed distinct and overlapping roles and subtly different temporal windows of action for each gene. The data also reveal a colinear-like effect of Cdx genes on Hox genes, with repression of Hox paralogy groups 1 and 2, and activation increasing from Hox group 5 to 11. We also highlight cases in which duplicated genes regulate distinct paralogous targets revealing pathway elaboration after whole genome duplication. CONCLUSIONS: Despite shared core pathways, Cdx paralogues have acquired distinct regulatory roles during development. This implies that the degree of functional overlap between paralogues is relatively low and that gene expression pattern alone should be used with caution when investigating the functional evolution of duplicated genes. We therefore suggest that developmental programmes were extensively rewired after whole genome duplication in the early evolution of vertebrates

    Standing genetic variation and the evolution of drug resistance in HIV

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    Drug resistance remains a major problem for the treatment of HIV. Resistance can occur due to mutations that were present before treatment starts or due to mutations that occur during treatment. The relative importance of these two sources is unknown. We study three different situations in which HIV drug resistance may evolve: starting triple-drug therapy, treatment with a single dose of nevirapine and interruption of treatment. For each of these three cases good data are available from literature, which allows us to estimate the probability that resistance evolves from standing genetic variation. Depending on the treatment we find probabilities of the evolution of drug resistance due to standing genetic variation between 0 and 39%. For patients who start triple-drug combination therapy, we find that drug resistance evolves from standing genetic variation in approximately 6% of the patients. We use a population-dynamic and population-genetic model to understand the observations and to estimate important evolutionary parameters. We find that both, the effective population size of the virus before treatment, and the fitness of the resistant mutant during treatment, are key-parameters that determine the probability that resistance evolves from standing genetic variation. Importantly, clinical data indicate that both of these parameters can be manipulated by the kind of treatment that is used.Comment: 33 pages 6 figure

    Registros sobre dor pós-operatória em crianças: uma análise retrospectiva de hospitais de Londrina, PR, Brasil Registros sobre el dolor post operatorio en niños: un análisis retrospectivo en hospitales de Londrina, PR, Brasil Notes of post-operative pain in children: a retrospective analyses of hospitals from Londrina, PR, Brazil

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    Toda cirurgia implica em lesão de tecidos, manipulação de estruturas e órgãos, sendo a dor uma conseqüência desse processo, que pode ser minimizada. Este estudo tem como objetivo caracterizar, retrospectivamente, o processo de manejo da dor pós-operatória a partir dos registros contidos em 300 prontuários de 280 crianças de 0 a 14 anos submetidas à cirurgia no ano de 2004 em três hospitais de Londrina, PR. O estudo indicou a existência de poucos registros sobre dor pós-operatória realizados por enfermeiras, sendo a maioria realizada por auxiliares ou técnicos de enfermagem. Esses achados evidenciam a necessidade de realização de pesquisas sobre manejo da dor pediátrica e os fatores que o influenciam.<br>Toda cirugía implica en lesión de tejidos, manipulación de estructuras y órganos, siendo el dolor una consecuencia de ese proceso, que puede ser minimizada. El presente estudio tiene como objetivo caracterizar, retrospectivamente, el proceso del manejo del dolor pos operatorio a partir de los registros contenidos en 300 prontuarios de 280 niños de 0 a 14 años sometidos a cirugía el año 2004 en tres hospitales de Londrina, PR, Brasil. El estudio indicó la existencia de pocos registros realizado por enfermeras, y la mayoría fue realizada por auxiliares o técnicos de enfermería. Los resultados evidencian la necesidad de la realización de pesquisas sobre el manejo del dolor pediátrico y los factores que lo influencian.<br>All surgical procedures involve tissue lesions, manipulation of structures and organs, causing pain which can be minimized during the process. The objective of this study is to characterize, retrospectively, the process of managing post-operative pain based on 300 medical records of 280 childre, who underwent surgery in 2004, in 3 hospitals located in Londrina, PR, Brazil. The study revealed that only a few nurses document post-operative pain, and that the majority of the records were made by nursing aides or technicians. The results have shown the need for research on pediatric pain management and the factors affecting them
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