90 research outputs found

    Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

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    Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

    Fever as a Cause of Hypophosphatemia in Patients with Malaria

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    Hypophosphatemia occurs in 40 to 60% of patients with acute malaria, and in many other conditions associated with elevations of body temperature. To determine the prevalence and causes of hypophosphatemia in patients with malaria, we retrospectively studied all adults diagnosed with acute malaria during a 12-year period. To validate our findings, we analyzed a second sample of malaria patients during a subsequent 10-year period. Serum phosphorus correlated inversely with temperature (n = 59, r = −0.62; P<0.0001), such that each 1°C increase in body temperature was associated with a reduction of 0.18 mmol/L (0.56 mg/dL) in the serum phosphorus level (95% confidence interval: −0.12 to −0.24 mmol/L [−0.37 to −0.74 mg/dL] per 1°C). A similar effect was observed among 19 patients who had repeat measurements of serum phosphorus and temperature. In a multiple linear regression analysis, the relation between temperature and serum phosphorus level was independent of blood pH, PCO2, and serum levels of potassium, bicarbonate, calcium, albumin, and glucose. Our study demonstrates a strong inverse linear relation between body temperature and serum phosphorus level that was not explained by other factors known to cause hypophosphatemia. If causal, this association can account for the high prevalence of hypophosphatemia, observed in our patients and in previous studies of patients with malaria. Because hypophosphatemia has been observed in other clinical conditions characterized by fever or hyperthermia, this relation may not be unique to malaria. Elevation of body temperature should be added to the list of causes of hypophosphatemia

    Drug-induced hyperthermia in Huntington's disease.

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    Contains fulltext : 57833.pdf (publisher's version ) (Closed access)Until now, only three patients with Huntington's disease (HD) and a neuroleptic malignant syndrome (NMS) have been reported in the literature. We describe four cases with advanced stage Huntington's disease who within a period of one year developed drug-induced hyperthermia, either the neuroleptic malignant syndrome, or the serotonin syndrome. Possible contributing factors that may have been specific for HD patients could be identified and included advanced neurological disease with severe illness, occurrence in summer, with possible infectious disease, dehydration, and pre-existing extra-pyramidal signs that may mask incipient NMS/serotonin syndrome. Measures to avoid these potentially lifethreatening conditions are discussed

    Variables Influencing Food Perception Reviewed for Consumer-Oriented Product Development

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    Consumer wishes have to be translated into product characteristics to implement consumer-oriented product development. Before this step can be made, insight in food-related behavior and perception of consumers is necessary to make the right, useful, and successful translation. Food choice behavior and consumers' perception are studied in many disciplines. Models of food behavior and preferences therefore were studied from a multidisciplinary perspective. Nearly all models structure the determinants related to the person, the food, and the environment. Consequently, the overview of models was used as a basis to structure the variables influencing food perception into a model for consumer-oriented product development. To this new model, referred to as food perception model, other variables like time and place as part of consumption moment were added. These are important variables influencing consumers' perception, and therefore of increasing importance to consumer-oriented product development nowadays. In further research, the presented food perception model is used as a tool to implement successful consumer-oriented product development

    Colombo Development Dialogues 2: water security and climate variability

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