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5 result(s) for "Marsden Fund"
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Ribosome Provisioning Activates a Bistable Switch Coupled to Fast Exit from Stationary Phase
Observations of bacteria at the single-cell level have revealed many instances of phenotypic heterogeneity within otherwise clonal populations, but the selective causes, molecular bases, and broader ecological relevance remain poorly understood. In an earlier experiment in which the bacterium Pseudomonas fluorescens SBW25 was propagated under a selective regime that mimicked the host immune response, a genotype evolved that stochastically switched between capsulation states. The genetic cause was a mutation in carB that decreased the pyrimidine pool (and growth rate), lowering the activation threshold of a preexisting but hitherto unrecognized phenotypic switch. Genetic components surrounding bifurcation of UTP flux toward DNA/RNA or UDP-glucose (a precursor of colanic acid forming the capsules) were implicated as key components. Extending these molecular analyses—and based on a combination of genetics, transcriptomics, biochemistry, and mathematical modeling—we show that pyrimidine limitation triggers an increase in ribosome biosynthesis and that switching is caused by competition between ribosomes and CsrA/RsmA proteins for the mRNA transcript of a positively autoregulated activator of colanic acid biosynthesis. We additionally show that in the ancestral bacterium the switch is part of a program that determines stochastic entry into a semiquiescent capsulated state, ensures that such cells are provisioned with excess ribosomes, and enables provisioned cells to exit rapidly from stationary phase under permissive conditions.
Eco-evolutionary implications of helminth microbiomes
The evolution of helminth parasites has long been seen as an interplay between host resistance to infection and the parasite's capacity to bypass such resistance. However, there has recently been an increasing appreciation of the role of symbiotic microbes in the interaction of helminth parasites and their hosts. It is now clear that helminths have a different microbiome from the organisms they parasitize, and sometimes amid large variability, components of the microbiome are shared among different life stages or among populations of the parasite. Helminths have been shown to acquire microbes from their parent generations (vertical transmission) and from their surroundings (horizontal transmission). In this latter case, natural selection has been strongly linked to the fact that helminth-associated microbiota is not simply a random assemblage of the pool of microbes available from their organismal hosts or environments. Indeed, some helminth parasites and specific microbial taxa have evolved complex ecological relationships, ranging from obligate mutualism to reproductive manipulation of the helminth by associated microbes. However, our understanding is still very elementary regarding the net effect of all microbiome components in the eco-evolution of helminths and their interaction with hosts. In this non-exhaustible review, we focus on the bacterial microbiome associated with helminths (as opposed to the microbiome of their hosts) and highlight relevant concepts and key findings in bacterial transmission, ecological associations, and taxonomic and functional diversity of the bacteriome. We integrate the microbiome dimension in a discussion of the evolution of helminth parasites and identify fundamental knowledge gaps, finally suggesting research avenues for understanding the eco-evolutionary impacts of the microbiome in host–parasite interactions in light of new technological developments.
Dopamine release in mushroom bodies of the honey bee (Apis mellifera L.) in response to aversive stimulation
In Drosophila melanogaster, aversive (electric shock) stimuli have been shown to activate subpopulations of dopaminergic neurons with terminals in the mushroom bodies (MBs) of the brain. While there is compelling evidence that dopamine (DA)-induced synaptic plasticity underpins the formation of aversive memories in insects, the mechanisms involved have yet to be fully resolved. Here we take advantage of the accessibility of MBs in the brain of the honey bee to examine, using fast scan cyclic voltammetry, the kinetics of DA release and reuptake in vivo in response to electric shock, and to investigate factors that modulate the release of this amine. DA increased transiently in the MBs in response to electric shock stimuli. The magnitude of release varied depending on stimulus duration and intensity, and a strong correlation was identified between DA release and the intensity of behavioural responses to shock. With repeated stimulation, peak DA levels increased. However, the amount of DA released on the first stimulation pulse typically exceeded that evoked by subsequent pulses. No signal was detected in response to odour alone. Interestingly, however, if odour presentation was paired with electric shock, DA release was enhanced. These results set the stage for analysing the mechanisms that modulate DA release in the MBs of the bee.
Global and regional ecological boundaries explain abrupt spatial discontinuities in avian frugivory interactions
Species interactions can propagate disturbances across space via direct and indirect effects, potentially connecting species at a global scale. However, ecological and biogeographic boundaries may mitigate this spread by demarcating the limits of ecological networks. We tested whether large-scale ecological boundaries (ecoregions and biomes) and human disturbance gradients increase dissimilarity among plant-frugivore networks, while accounting for background spatial and elevational gradients and differences in network sampling. We assessed network dissimilarity patterns over a broad spatial scale, using 196 quantitative avian frugivory networks (encompassing 1496 plant and 1004 bird species) distributed across 67 ecoregions, 11 biomes, and 6 continents. We show that dissimilarities in species and interaction composition, but not network structure, are greater across ecoregion and biome boundaries and along different levels of human disturbance. Our findings indicate that biogeographic boundaries delineate the world’s biodiversity of interactions and likely contribute to mitigating the propagation of disturbances at large spatial scales.
Effectiveness of health checks conducted by nurses in primary care: final results of the OXCHECK study
Abstract Objective: To determine the effectiveness of health checks, performed by nurses in primary care, in reducing risk factors for cardiovascular disease and cancer. Design: Randomised controlled trial. Setting: Five urban general practices in Bedfordshire. Subjects: 2205 men and women who were randomly allocated a first health check in 1989-90 and a re-examination in 1992-3 (the intervention group); 1916 men and women who were randomly allocated an initial health check in 1992-3 (the control group). All subjects were aged 35-64 at recruitment in 1989. Main outcome measures: Serum total cholesterol concentration, blood pressure, body mass index, and smoking prevalence (with biochemical validation of cessation); self reported dietary, exercise, and alcohol habits. Results: Mean serum total cholesterol was 3.1% lower in the intervention group than controls (difference 0.19 mmol/l (95% confidence interval 0.12 to 0.26); in women it was 4.5% lower (P<0.0001) and in men 1.6% (P<0.05), a significant difference between the sexes (P<0.01). Self reported saturated fat intake was also significantly lower in the intervention group. Systolic and diastolic blood pressures and body mass index were respectively 1.9%, 1.9%, and 1.4% lower in the intervention group (P<0.005 in all cases). There was a 3.9% (2.4 to 5.3) difference in the percentage of subjects with a cholesterol concentration >/=8 mmol/l, but no significant differences in the number with diastolic blood pressure >/=100 mm Hg or body mass index >/=30 kg/m2. There was no significant difference between the two groups in prevalence of smoking or excessive alcohol use. Annual rechecks were no more effective than a single recheck at three years, but health checks led to a significant increase in visits to the nurse according to patients' degree of cardiovascular risk. Conclusions: The benefits of health checks were sustained over three years. The main effects were to promote dietary change and reduce cholesterol concentrations; small differences in blood pressure may have been attributable to accommodation to measurement. The benefits of systematic health promotion in primary care are real, but must be weighed against the costs in relation to other priorities. Key messages Key messages There is little effect on smoking or alcohol use, and more targeted approaches to modifying these behaviours may be appropriate Systematic implementation of health checks might lead to a reduction in risk of myocardial infarction among those who attend of about 5-15%; men, who are at higher risk, show less change than women Health checks consume substantial resources, and their effect is attenuated by non-attendance The benefits of health promotion through primary care must be weighed against their costs and in relation to other priorities