Biomedical subjects
Publications and source records attributed to Chris Nelson.
We describe a method of combining STEM imaging functionalities with nanoarea parallel beam electron diffraction on a modern TEM. This facilitates the search for individual particles whose diffraction patterns are needed for diffractive imaging or structural studies of nanoparticles. This also lays out a base for 3D diffraction data collection.
AIMS: To examine the hypothesis that patients who present in the UK to detoxification services differ from patients who present with severe alcohol-induced liver disease (ALD) with respect to severity of dependence on alcohol and other features of their drinking history. METHODS: Levels of alcohol dependence were assessed in 34 patients with severe ALD, all of whom were cirrhotic, and 34 subjects from a residential alcohol detox centre in Southampton using the Severity of Alcohol Dependence Questionnaire (SADQ). During interview, various aspects of participants' alcohol consumption were recorded, including total monthly consumption, whom they usually drank with and where, and, if applicable, what caused them to start drinking heavily. Social circumstances were also noted, including participants' employment and marital status. RESULTS: Among ALD patients, 58% scored none/mild on the SADQ, 32% moderate and 9% severe. In contrast, 76% of the detox group were graded severe and 34% moderate (P < 0.001). ALD patients were also significantly older, had lower scores on the Alcohol Use Disorders Identification Test, tended to drink less alcohol, were more likely to be in a stable relationship, were less likely to be unemployed and gave different reasons for starting to drink heavily. The ALD group were most likely to have started drinking heavily for social reasons, whereas subjects in the detox group were most likely to have started drinking heavily as a result of relationship or money problems. CONCLUSION: Patients attending a liver unit and patients admitted to a detoxification unit were separate but overlapping populations of alcohol misusers. Perhaps these two populations of alcohol misusers are likely to require different approaches for effective detection, intervention and treatment.
Using laboratory experiments, simulation models, and analytical techniques, we examined the impact of dispersal on the mean densities of patchily distributed populations. Even when dispersal leads to no net additions or removals of individuals from a population, it may nonetheless increase mean population densities if the net immigration rate is positive when populations are growing and negative when they are declining. As a model system for exploring this phenomenon, we used the yeastlike fungus Aureobasidium pullulans. In a laboratory experiment, we showed that dispersal can both ensure persistence and increase mean population densities even when dispersal among populations causes no direct addition or loss of fungal cells. From the laboratory data, we constructed a plausible model of A. pullulans dynamics among apple leaves within an orchard. This simulation model demonstrated that the effect of dispersal on mean densities is enhanced by three factors: weak density dependence of the dynamics within populations, high environmental variability affecting population growth rates, and lack of synchrony among the fluctuations of populations. Using an analytical model, we showed that the underlying mechanisms for this phenomenon are general, suggesting that a large effect of dispersal on mean population densities is possible in many natural systems.
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The budding yeast Saccharomyces cerevisiae differentiates into filamentous invasively growing forms under conditions of nutrient limitation. This response is dependent on the transcription factor Ste12 and on the mating pheromone-response mitogen-activated protein (MAP) kinase cascade, but a mechanism for regulation of Ste12 by nutrient limitation has not been defined. Here we show that Ste12 function in filamentous growth is regulated by the cyclin-dependent kinase Srb10 (also known as Cdk8), which is associated with the RNA polymerase II holoenzyme. Srb10 inhibits filamentous growth in cells growing in rich medium by phosphorylating Ste12 and decreasing its stability. Under conditions of limiting nitrogen, loss of Srb10 protein and kinase activity occurs, with a corresponding loss of Ste12 phosphorylation. Mutation of the Srb10-dependent phosphorylation sites increases pseudohyphal development but has no effect on the pheromone response of haploid yeast. Srb10 kinase activity is also regulated independently of the mating pheromone-response pathway. This indicates that Srb10 controls Ste12 activity for filamentous growth in response to nitrogen limitation and is consistent with the hypothesis that Srb10 regulates gene-specific activators in response to physiological signals to coordinate gene expression with growth potential.