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Biomedical subjects

A D Peters

Publications and source records attributed to A D Peters.

13 recordsLinked to original sources

Properties of ethylmethane sulfonate-induced mutations affecting life-history traits in Caenorhabditis elegans and inferences about bivariate distributions of mutation effects.

The homozygous effects of ethylmethane sulfonate (EMS)-induced mutations in Caenorhabditis elegans are compared across life-history traits. Mutagenesis has a greater effect on early than late reproductive output, since EMS-induced mutations tend to cause delayed reproduction. Mutagenesis changes the mean and variance of longevity much less than reproductive output traits. Mutations that increase total or early productivity are not detected, but the net effect of mutations is to increase and decrease late productivity to approximately equal extents. Although most mutations decrease longevity, a mutant line with increased longevity was found. A flattening of mortality curves with age is noted, particularly in EMS lines. We infer that less than one-tenth of mutations that have fitness effects in natural conditions are detected in the laboratory, and such mutations have moderately large effects ( approximately 20% of the mean). Mutational correlations for life-history traits are strong and positive. Correlations between early or late productivity and longevity are of similar magnitude. We develop a maximum-likelihood procedure to infer bivariate distributions of mutation effects. We show that strong mutation-induced genetic correlations do not necessarily imply strong directional correlations between mutational effects, since correlation is also generated by lines carrying different numbers of mutations.

Animals↗

A test for epistasis among induced mutations in Caenorhabditis elegans.

Synergistic epistasis, in which deleterious mutations tend to magnify each other's effects, is a necessary component of the mutational deterministic hypothesis for the maintenance of sexual production. We tested for epistasis for life-history traits in the soil nematode Caenorhabditis elegans by inducing mutations in two genetic backgrounds: a wild-type strain and a set of genetically loaded lines that contain large numbers of independent mildly detrimental mutations. There was no significant difference between the effect of new mutations on the wild-type background and the genetically loaded background for four out of five fitness correlates. In these four cases, the maximum level of epistasis compatible with the data was very low. The fifth trait, late productivity, is not likely to be an important component of fitness. This suggests either that specific environmental conditions are required to cause epistasis or that synergistic epistasis is not a general phenomenon. We also suggest a new mechanism by which deleterious mutations may provide an advantage to sexual reproduction under low selection coefficients.

Analysis of Variance↗

High frequency of cryptic deleterious mutations in Caenorhabditis elegans.

Deleterious mutations with very small phenotypic effects could be important for several evolutionary phenomena, but the extent of their contribution has been unknown. Fitness effects of induced mutations in lines of Caenorhabditis elegans were measured using a system for which the number of deleterious point mutations in the DNA can be estimated. In fitness assays, only about 4 percent of the deleterious mutations fixed in each line were detectable. The remaining 96 percent, though cryptic, are significant for mutation load and, potentially, for the evolution of sex.

Animals↗

The Red Queen and Fluctuating Epistasis: A Population Genetic Analysis of Antagonistic Coevolution.

Host-parasite coevolution has been shown to provide an advantage to recombination, but the selective mechanism underlying this advantage is unclear. One possibility is that recombination increases the frequency of advantageous genotypes that are disproportionately rare because of fluctuating epistasis. However, for this mechanism to work, epistasis for fitness must fluctuate over a very narrow timescale: two to five generations. Alternatively, recombination may speed up the response to directional selection by breaking up linkage disequilibria that decrease additive genetic variance. Here we analyze the results of a numerical simulation of host-parasite coevolution to assess the importance of these two mechanisms. We find that linkage disequilibria may tend to increase, rather than decrease, additive genetic variance. In addition, the sign of epistasis changes every two to five generations under several of the parameter values investigated, and epistasis and linkage disequilibrium are frequently of opposite signs. These results are consistent with the idea that selection for recombination is mediated by fluctuating epistasis. Finally, we explore the conditions under which an allele causing free recombination can spread in a nonrecombining host population and find general agreement between the predictions of a population genetic model of fluctuating epistasis and our simulation model.

Red Queen↗

Methadone treatment in the Scottish context: outcomes of a community-based service for drug users in Lothian.

Few studies investigating the effectiveness of methadone treatment for opiate dependence have emanated from the UK. The core feature of treatment offered by Lothian Health's Community Drug Problems Service involves the prescribing of methadone by the client's general practitioner. Of a cohort of 494 daily users of opiates attending the service, 39% remained in treatment for at least 12 months. Up to 2 years in-treatment follow-up revealed significant improvement in injecting and criminal behaviour. There were no HIV seroconversions reported during the treatment period. There was no improvement in injection equipment sharing, condom use, illicit drug use or employment status. 'Satisfactory' discharge was achieved for 40% of those in treatment for at least 6 months. These results are largely consistent with the outcomes of methadone programmes elsewhere.

Adolescent↗

Testing for epistasis between deleterious mutations.

Determining the way in which deleterious mutations interact in their effects on fitness is crucial to numerous areas in population genetics and evolutionary biology. For example, if each additional mutation leads to a greater decrease in log fitness than the last (synergistic epistasis), then the evolution of sex and recombination may be favored to facilitate the elimination of deleterious mutations. However, there is a severe shortage of relevant data. Three relatively simple experimental methods to test for epistasis between deleterious mutations in haploid species have recently been proposed. These methods involve crossing individuals and examining the mean and/or skew in log fitness of the offspring and parents. The main aim of this paper is to formalize these methods, and determine the most effective way in which tests for epistasis could be carried out. We show that only one of these methods is likely to give useful results: crossing individuals that have very different numbers of deleterious mutations, and comparing the mean log fitness of the parents with that of their offspring. We also reconsider experimental data collected on Chlamydomonas moewussi using two of the three methods. Finally, we suggest how the test could be applied to diploid species.

Animals↗

Gender differences in HIV risk behaviour of injecting drug users in Edinburgh.

A multi-site sample of currently-injecting drug users (IDUs) comprising 344 men and 136 women was recruited in Edinburgh. Sixty-seven per cent of the sample said they had at some time used injecting equipment already used by another person and 25% admitted doing so in the 6 months before interview. Whereas women who injected with used equipment obtained it predominantly from a sexual partner, for men the source was more often a close friend or someone whose HIV status they were unlikely to know. In the 6 months before interview, 40% of men, compared with 20% of women, had more than one heterosexual partner. This difference was associated with a higher proportion of men with steady partners also having casual partners. Women IDUs were more likely to have regular partners who injected (57% vs 26%). Though sharing of injecting equipment has already diminished in Edinburgh, further measures are needed to eliminate it. For injectors here, the risk of infection from unprotected heterosexual intercourse may now be greater than that from sharing injecting equipment, particularly for women. Other methods of encouraging changes in sexual behaviour need to be investigated and successful ones promoted.

Adolescent↗

Effect of polymerization mode of a dual-cured resin cement on time-dependent shear bond strength to porcelain.

PURPOSE: To evaluate the shear bond strengths to porcelain and setting times of a dual-cured resin cement with light/chemical curing (dual) or chemical only curing versus time. MATERIALS AND METHODS: Variolink resin cement was bonded to specimens of etched, silanated porcelain. Groups of specimens were cured by dual cured or by chemical curing only. Shear bond strengths were recorded at 2, 3, 5, 60 minutes and 24 hours for dual cured and at 10, 20, 40, 50, 60 minutes and 24 hours for chemical-cured only after mixing. Kinetic-temperature profiles of dual and chemical curing modes of cement were calculated. RESULTS: Maximum bond strengths and time to attainment were 17.5 +/- 2.7 MPa at 60 minutes for chemical-cured and 26.1 +/- 2.3 MPa at 5 minutes for dual-cured. The peak in the kinetic-temperature setting profiles were 14.1 +/- 0.9 minutes for chemical curing and 52.2 +/- 5.2 seconds for dual curing. Dual curing provided significantly higher shear bond strengths versus chemical curing at both the 60-minute and 24-hour time periods.

Analysis of Variance↗

Edinburgh drug users: are they injecting and sharing less?

OBJECTIVE: To describe epidemiological trends in injecting and equipment sharing among a sample drawn from a drug-using population with a high rate of HIV infection. DESIGN: A structured interview was administered prior to treatment to cross-sectional samples of drug users over the period 1988-1991. Reports of injecting, sharing and HIV infection were compared annually. SETTING: Lothian Health Board's Community Drug Problems Service is a secondary level service offering harm reduction and treatment of dependency. PARTICIPANTS: A total of 734 consecutively referred drug users resident in Edinburgh. Re-referrals in the same calendar year were excluded. MEASURES: History of injecting and sharing, recent injecting and sharing, HIV testing history, drugs used in previous month and substitute prescription status. RESULTS: Large reductions in the frequency of injecting were found over the 4 years even among those who were not receiving oral substitutes. More participants in latter years were receiving prescriptions combining opioids and benzodiazepines. Fewer of those interviewed latterly had ever shared injecting equipment. Among recent injectors just as many share equipment as previously. HIV prevalence did not vary significantly over the period. An HIV prevalence of 19% was reported among recent injectors. CONCLUSIONS: Edinburgh's drug users are engaging in far safer drug-taking behaviour than previously. Levels of HIV in this population suggest that the epidemic is being contained. A small number persist in high risk drug-related activities. Further investigation of the characteristics of these individuals and the need to develop novel methods of influencing their behaviour are recommended.

Adult↗

A pilot survey of client opinion of the Lothian Community Drug Problem Service: likes, dislikes, efficacy and improvements.

An open ended unstructured questionnaire was used to find out the opinion of clients of the Community Drug Problem Service of Lothian Health Board, concerning how the service had helped them and for suggestions for improvement. A total of 63 questionnaires were returned over a six month period. Analysis showed that 77% of respondents valued counselling services but 26% complained of too low oral substitute drug dosage. Improvement in personal development, stabilised drug use, less criminality and stopping injecting were reported as being the main benefits. A more detailed self reporting questionnaire will be developed from this pilot study to answer some of the questions raised and for use as a routine part of ongoing service monitoring and evaluation.

Community Health Services↗