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Biomedical subjects

A Fenton

Publications and source records attributed to A Fenton.

At least 19 recordsLinked to original sources

Pathogen responses to host immunity: the impact of time delays and memory on the evolution of virulence.

Current analytical models of the mammalian immune system typically assume a specialist predator-prey relationship between invading pathogens and the active components of the immune response. However, in reality, the specific immune system is not immediately effective following invasion by a novel pathogen. First, there may be an explicit time delay between infection and immune initiation and, second, there may be a gradual build-up in immune efficacy (for instance, during the period of B-cell affinity maturation) during which the immune response develops, before reaching maximal specificity to the pathogen. Here, we use a novel theoretical approach to show that these processes, together with the presence of long-lived immune memory, decouple the immune response from current pathogen levels, greatly changing the dynamics of the pathogen-immune system interaction and the ability of the immune response to eliminate the pathogen. Furthermore, we use this model to show how distributed primary immune responses combine with immune memory to greatly affect the optimal virulence of the pathogen, potentially resulting in the evolution of highly virulent pathogens.

Animals↗

The relationship between polychlorinated biphenyls in blubber and levels of nematode infestations in harbour porpoises, Phocoena phocoena.

Post-mortem examinations of harbour porpoises, Phocoena phocoena, regularly reveal heavy parasitic worm burdens. These same post-mortem records show varying levels of polychlorinated biphenyls (PCBs) accumulating in the blubber of porpoises. Although a number of papers have documented geospatial and temporal changes of PCBs and their detrimental effects on marine mammal health, as yet none have examined their role in determining nematode burdens in wild marine mammal populations. Using a data set consisting of harbour porpoises stranded in the UK between 1989 and 2002, we found a significant, positive association between PCB levels and nematode burdens, although the nature of the relationship was confounded with porpoise sex, age and cause of death. It was also apparent that individuals with the heaviest infestations of nematodes did not have the highest PCB level: while PCBs are important, they are clearly not the sole determinants of nematode burdens in wild populations of the harbour porpoise around the UK.

Adipose Tissue↗

The impact of parasite manipulation and predator foraging behavior on predator-prey communities.

Parasites are known to directly affect their hosts at both the individual and population level. However, little is known about their more subtle, indirect effects and how these may affect population and community dynamics. In particular, trophically transmitted parasites may manipulate the behavior of intermediate hosts, fundamentally altering the pattern of contact between these individuals and their predators. Here, we develop a suite of population dynamic models to explore the impact of such behavioral modifications on the dynamics and structure of the predator-prey community. We show that, although such manipulations do not directly affect the persistence of the predator and prey populations, they can greatly alter the quantitative dynamics of the community, potentially resulting in high amplitude oscillations in abundance. We show that the precise impact of host manipulation depends greatly on the predator's functional response, which describes the predator's foraging efficiency under changing prey availabilities. Even if the parasite is rarely observed within the prey population, such manipulations extend beyond the direct impact on the intermediate host to affect the foraging success of the predator, with profound implications for the structure and stability of the predator-prey community.

Animals↗

Patterns of parasite aggregation in the wild European rabbit (Oryctolagus cuniculus).

Understanding the factors controlling the distribution of parasites within their host population is fundamental to the wider understanding of parasite epidemiology and ecology. To explore changes in parasite aggregation, Taylor's power law was used to examine the distributions of five gut helminths of the wild rabbit. Aggregation was found to be a dynamic process that varied with year, season, host sex, age class, and myxomatosis. Yearly and seasonal changes are thought, in the main, to be the result of variations in weather conditions acting upon infectious stages (or intermediate hosts). Evidence in support of this was the comparatively low degree of fluctuation in the aggregation of the pinworm, Passalurus ambiguus, as the infectious stage of this parasite is likely to be less susceptible to environmental variation. Host age had a marked effect on the level of aggregation of all parasites, but this effect varied between parasite species. P. ambiguus, Trichostrongylus retortaeformis and Cittotaenia denticulata aggregation were lower in adult than juvenile rabbits whilst Graphidium strigosum and Mosgovoyia pectinata aggregation tended to increase with age. Host immunity is thought to be responsible for these differences. Differences in aggregation for different parasites were also seen when the rabbit population was split into males and females. Myxomatosis had a marked effect on helminth distribution with substantially less aggregation in rabbits showing clinical signs of the disease.

Age Factors↗

Passive and active place avoidance as a tool of spatial memory research in rats.

A modified model of the arena described by Bures et al. (Bures J, Fenton AA, Kaminsky Y, Zinyuk L. Place cells and place navigation, Proc. Natl. Acad. Sci. USA. 1997a;94:343-350) was applied to the place learning of adult male rats in two different avoidance paradigms. In the passive avoidance task rats exploring a stationary circular arena had to avoid a 60 degrees sector entering of which was punished by mild footshocks. Intramaze as well as extramaze cues could be used for adequate solution of this task. In the active avoidance paradigm rats were trained to avoid a room frame defined sector (e.g. North-East) of a slowly rotating arena the movement of which forced the animals to rely on extramaze cues and to ignore intramaze information. Rats had to find an active solution of the task since otherwise they were passively transported into the room frame defined punished zone. The suitability of these tasks for testing spatial abilities of rats is discussed.

Animals↗

Re-assessing the infection strategies of the entomopathogenic nematode Steinernema feltiae (Rhabditidae; Steinernematidae).

Previous studies have indicated that between 60 and 80% of a population of entomopathogenic nematodes do not infect their insect hosts at any one period in time. Two hypotheses explain this behaviour: the first that there is a subpopulation of non-infectious nematodes and the second that the non-infectious group is created by inhibitory cues derived from infected insects. Through an experimental approach with the Galleria mellonella-Steinernema feltiae system we show that both mechanisms operate together. When conditions for infection were optimized, the sum of individual infection behaviours was similar to the number infecting as a population, implying observed infection rates are driven by intrinsic mechanisms. In addition, there was evidence that an infected host released a chemical cue into the environment which inhibited subsequent levels of infection. This degree of inhibition was independent of the number of infecting nematodes. Both these mechanisms are dynamic, so the observed proportion of infectious nematodes depended heavily on the time of exposure. The implications of these findings for both the design of laboratory trials and the use of entomopathogenic nematodes in biological control are discussed.

Animals↗

A regulatory RNA (PrrB RNA) modulates expression of secondary metabolite genes in Pseudomonas fluorescens F113.

The GacS-GacA two-component signal transduction system, which is highly conserved in gram-negative bacteria, is required for the production of exoenzymes and secondary metabolites in Pseudomonas spp. Screening of a Pseudomonas fluorescens F113 gene bank led to the isolation of a previously undefined locus which could restore secondary metabolite production to both gacS and gacA mutants of F113. Sequence analysis of this locus demonstrated that it did not contain any obvious Pseudomonas protein-coding open reading frames or homologues within available databases. Northern analysis indicated that the locus encodes an RNA (PrrB RNA) which is able to phenotypically complement gacS and gacA mutants and is itself regulated by the GacS-GacA two-component signal transduction system. Primer extension analysis of the 132-base transcript identified the transcription start site located downstream of a sigma(70) promoter sequence from positions -10 to -35. Inactivation of the prrB gene in F113 resulted in a significant reduction of 2, 4-diacetylphloroglucinol (Phl) and hydrogen cyanide (HCN) production, while increased metabolite production was observed when prrB was overexpressed. The prrB gene sequence contains a number of imperfect repeats of the consensus sequence 5'-AGGA-3', and sequence analysis predicted a complex secondary structure featuring multiple putative stem-loops with the consensus sequences predominantly positioned at the single-stranded regions at the ends of the stem-loops. This structure is similar to the CsrB and RsmB regulatory RNAs in Escherichia coli and Erwinia carotovora, respectively. Results suggest that a regulatory RNA molecule is involved in GacA-GacS-mediated regulation of Phl and HCN production in P. fluorescens F113.

Bacterial Proteins↗

The effects of oviposition aggregation on the incidence of sheep blowfly strike.

The distribution of a parasite population within its natural host population can have a significant influence on the dynamics of both the host and parasite populations. The majority of parasite species are typically distributed in an aggregated manner within the host population, leaving most hosts lightly infected and a few hosts supporting very large parasite burdens. This paper presents a consideration of the effects of aggregation on the incidence of ovine cutaneous myiasis caused by the sheep blowfly, Lucilia sericata (Meigen). Using simulation analysis, the mechanisms causing larval aggregation are included in the model, allowing the consequences for control to be investigated. By explicitly incorporating host susceptibility, it becomes apparent that early in the season, strategies targeting the blowfly population may prove more effective in suppressing strike levels, whereas later in the season, treatment of the sheep population may be more beneficial. The analysis also shows that the greater the degree of aggregation, the fewer sheep that become struck and, hence, suggests that increasing the heterogeneity in susceptibility amongst a flock of sheep restricts strikes to relatively few sheep. Providing the highly-susceptible sheep could be identified, concentrating strikes on a low number of sheep would allow fewer sheep to be treated, leading to a more efficient means of controlling the blowfly population and suppressing strike.

Animals↗

The effect of farm management strategies on the incidence of sheep strike in Britain: a simulation analysis.

A deterministic model is used to simulate the seasonal incidence of sheep myiasis (strike) on farms in Britain and to explore the effects of different farm management strategies on strike incidence. The model is based on two sub-components: the seasonal pattern of abundance of the primary agent of sheep myiasis in northwest Europe, the blowfly Lucilia sericata and the range of factors known to influence ewe and lamb susceptibility to strike. The results of these simulations show that familiar farm management strategies, such as shearing, reduction in scouring caused by endoparasitic worms and insecticide use can have an important role in the reduction of strike incidence in ewes and lambs. However, the effectiveness of these techniques can be highly dependent of their timing in relation to seasonal changes in blowfly abundance and the effects of temperature and rainfall.

Animal Husbandry↗

The incidence of sheep strike by Lucilia sericata on sheep farms in Britain: a simulation model.

Using a combination of a temperature-dependent simulation of the population dynamics of Lucilia sericata and a logistic model of sheep susceptibility, based on patterns of faecal soiling, fleece length and fleece humidity, a deterministic simulation model has been constructed to predict the incidence of sheep strike by L. sericata on lambs and ewes in Britain. Strikes are assigned to individual sheep in the flock according to a negative binomial distribution. The model shows that the majority of the first strikes of the season occur equally on ewes and lambs, when ewe fleeces are long and before lamb susceptibility increases though faecal soiling. With each subsequent generation of gravid blowflies, however, a greater proportion of strikes occur on lambs, while the number of strikes observed on ewes remains relatively consistent throughout the season. The increase in strike of lambs is due to the seasonal increase in lamb faecal soiling, associated with rising helminth infections and lamb fleece growth. The model shows that at the beginning of the season the incidence of strike is limited by the low number of flies present: towards the end of seasons, however, the blowfly population had grown large enough for the number of strikes to be limited by the number of susceptible ewes and lambs. The model shows that the seasonal incidence of strike is highly sensitive to the interactions between temperature, rainfall and would length. Strike was most prevalent under warm, wet conditions. However, there is a critical period during spring, where the short fleeces of lambs and ewes, in the latter case due to shearing, results in the desiccation of egg batches. If this coincides with dry conditions, the high levels of mortality result in suppression of the fly population and a reduction in the subsequent incidence of strike.

Animals↗

Role of 2,4-Diacetylphloroglucinol in the Interactions of the Biocontrol Pseudomonad Strain F113 with the Potato Cyst Nematode Globodera rostochiensis.

The potato cyst nematode Globodera rostochiensis is an important pest of potato (Solanum tuberosum). Pseudomonas fluorescens F113, which produces 2,4-diacetylphloroglucinol (DAPG), was investigated as a potential biocontrol agent against G. rostochiensis. Exposure of nematode cysts to the pseudomonad, under in vitro conditions or in soil microcosms, almost doubled the ability of the eggs to hatch. The percentage of mobile juveniles was reduced threefold following their incubation in the presence of the pseudomonad, both in vitro and in soil. Results obtained with a transposon-induced DAPG-negative biosynthetic mutant of F113 and its complemented derivative with restored DAPG synthesis showed that the ability of strain F113 to produce DAPG was responsible for the increase in hatch ability and the reduction in juvenile mobility. Similar effects on egg hatch ability and juvenile mobility of G. rostochiensis were obtained in vitro by incubating nematode cysts and juveniles, respectively, in the presence of synthetic DAPG. DAPG-producing P. fluorescens F113 is proposed as a potential biocontrol inoculant for the protection of potato crops against the potato cyst nematode.

Journal Article↗

Improved delivery of biocontrol Pseudomonas and their antifungal metabolites using alginate polymers.

Alginate polymer was evaluated as a carrier for seed inoculation with a genetically modified strain Pseudomonas fluorescens F113LacZY, which protects sugar-beet against Pythium-mediated damping-off. F113LacZY survived in alginate beads at 5 log10 CFU/bead or higher counts for 8 weeks of storage, regardless of the conditions of incubation. In plant inoculation experiments, colonisation of the growing area of the root by F113LacZY, derived from alginate beads placed in the soil next to the seed or from an alginate coating around the seeds, was improved compared with application of just free cells of the strain. F113LacZY trapped in alginate beads was an effective producer of antifungal phloroglucinols as indicated by direct HPLC quantification of phloroglucinols and in vitro inhibition of both the indicator bacterium Bacillus subtilis A1 and the pathogenic fungus Pythium ultimum. Alginate polymer represents a promising carrier for the delivery of biocontrol inoculants for root colonisation and production of antifungal metabolites.

Alginates↗

The Scottish tonsillectomy audit. Audit Sub-Committee of the Scottish Otolaryngological Society.

Regional specialist societies offer a valuable mechanism for the conduct of medical audit. The experience of the audit sub-committee of The Scottish Otolaryngological Society in conducting an audit on laryngeal cancer encouraged us to undertake a larger audit of tonsillectomy practice in Scotland. Although the number of tonsillectomies performed has declined over the last 10 years, they still account for about 20 per cent of all operations performed by otolaryngologists and as such are a major consumer of resources (Personal communication--Directorate of Information Services, Information and Statistics Division. NHS in Scotland, Management Executive, Edinburgh). The Scottish tonsillectomy audit was devised to define current practice, review indications for surgery and recommend such modifications in practice as may be necessary to optimise patient care and the use of resources. Funding was obtained from the Clinical Resource and Audit Group (CRAG) of the Scottish Home and Health Department. Data on current practice was collected during the period February 1992 to January 1993. Proformas were completed by medical, administrative and secretarial staff in all participating hospitals, collected by an audit secretary and passed to the relevant data collection centre. Data was then entered into a specially designed database before being forwarded to the audit co-ordinator based in Dundee for collation. Six and 12 months following surgery, all inpatients were sent a questionnaire to obtain data on the efficacy of the operation. Data were obtained from a total of 9,773 patients. Two thousand and seventy-nine of these were seen as both outpatients and inpatients, 4,309 were outpatients only and 3,385 were inpatients only. Four thousand, one hundred and one patients returned at least one follow-up questionnaire. The topics audited included source and reason for referral, indications for surgery, grade of staff involved, type of surgery and length of stay in hospital. In agreement with previous studies (H.M.S.O., 1989), differences were found in the rates of tonsillectomy performed in different Health Boards. Although the highest referral and operation rates were found in the Highland region, referral and operation rates did not correlate in all other areas. Recurrent tonsillitis was the most frequent principal reason for the decision to operate although there were differences between Health Boards for other indications including obstructive symptoms. Most patients had symptoms for two to three years although some patients had been affected for 40 years prior to being listed for tonsillectomy. Some area ENT services were consultant-based while others involved more junior staff. The grade of staff involved did not appear to affect the decision made at the Outpatient Department (OPD) or the outcome of the operation. Ninety-eight per cent of patients who returned the questionnaire were glad that the operation had been performed. Recommendations regarding changes in tonsillectomy practice are given.

Adenoidectomy↗