The maintenance of polygenic variation through a balance between mutation and stabilizing selection.
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Alleles↗
Biomedical subjects
N H Barton
Publications and source records attributed to N H Barton.
The effects of linkage and density-dependent regulation on gene flow.
The rate of gene flow across a hybrid zone may be reduced by the presence of a physical barrier, by a reduction of population density caused by reduced fitness of hybrids (the "hybrid sink" effect), and by linkage. If the reduction in hybrid fitness is not extreme, the strength of the barrier to gene flow caused by these effects is B = w(rho *+/rho *0)2(W*+/W*0)(2/R + 1/r). Here, w is the width of the cline; rho * is the carrying capacity; W* is the mean fitness of the population, excluding effects of density; R is the strength of density-dependent regulation; and r is the harmonic mean recombination rate between the locus whose flow is being calculated, and loci under selection. +, 0 denote populations outside the hybrid zone, and at its centre, respectively. This relation is illustrated using data from hybrid zones in Bombina and Podisma, and its implications for interpretation of data from nature are discussed.
Animals↗
A quasi-equilibrium theory of the distribution of rare alleles in a subdivided population.
The conditional average frequency of rare alleles has been shown in simulations to provide a simple and robust estimator of the number of individuals exchanged between local populations in an island model (Nm). This statistic is defined as the average frequency of an allele in those samples in which the allele is present. Here, we show that the conditional average frequency can be calculated from the distribution of allele frequencies. It is a measure of the spread of this distribution, and so is analogous to the standardised variance, FST. Analytic predictions for the island model of migration agree well with the corresponding simulation results. These predictions are based on the assumption that the rare alleles found in samples have reached a "quasi-equilibrium" distribution. As well as relating the conditional average frequency to the underlying allele frequency distribution, our results provide a more accurate method of estimating Nm from the conditional average frequency of private alleles in samples of different sizes.
Alleles↗
Pharmacology, tolerance, and antiviral activity of vidarabine monophosphate in humans.
Vidarabine (adenine arabinoside) is a purine nucleoside useful in humans for therapy of herpes simplex virus encephalitis and herpes zoster virus infections in immunocompromised patients. However, the potential usefulness of vidaribine is limited by its poor solubility, which requires continuous infusion in relatively large volumes of intravenous fluid. Vidarabine 5'-monophosphate is highly soluble and has the advantage that it can be administered intermittently intramuscularly or intravenously. In a clinical, pharmacokinetic study, plasma levels and urinary excretion of vidarabine 5'-monophosphate were determined after intravenous and intramuscular administration in 29 immunosuppressed patients with herpes simplex or zoster virus infections at dosages of 15 to 30 mg/kg per day administered for 5 days. As determined by high-pressure liquid chromatography, vidarabine 5'-monophosphate was metabolized in a fashion comparable to the metabolism of vidarabine and its major metabolite in plasma was arabinosyl hypoxanthine. After administration, 40 to 50% of the vidarabine 5'-monophosphate was recovered from the urine as arabinosyl hypoxanthine, and 3 to 4% was recovered as vidarabine. Determinations of areas under the curve for arabinosyl hypoxanthine were not statistically different by dosage for intramuscular or intravenous routes of administration. At all dosages studied, viral clearance appeared to occur with therapy. The advantage of increased solubility will lead to controlled clinical investigations in which vidarabine 5'-monophosphate is administered by intramuscular or intravenous routes against targeted human herpesvirus infections.
Antiviral Agents↗
Acyclovir: mechanism of action, pharmacokinetics, safety and clinical applications.
Acyclovir is a new antiviral drug that acts as a specific inhibitor of herpesvirus DNA polymerase. It shows good in vitro activity against herpes simplex and varicella-zoster viruses. The drug may be administered topically to the skin, intravenously, orally, or topically to the eye (only topical and intravenous preparations are currently available). Acyclovir kinetics are described by a two-compartment open model. The drug and its metabolites are excreted by the kidney via glomerular filtration and tubular secretion. Dosage adjustment is required in patients with renal failure. Safety and tolerance studies in animals and humans have shown acyclovir to be very well tolerated. The most important adverse effect is crystalluria and elevated serum creatinine related to bolus intravenous administration. Other reported adverse effects include infusion site inflammation and rash. Topical acyclovir is effective for treating initial genital herpes and mucocutaneous herpes in the compromised host, but has not been shown to be clinically useful for recurrent labial or genital herpes. Intravenous acyclovir is effective for mucocutaneous herpes infections in the compromised host and initial genital herpes in the normal host; it is being evaluated for the treatment of herpes simplex virus encephalitis and varicella-zoster infections. An investigational oral preparation may prove to be effective therapy for both initial and recurrent genital herpes. Acyclovir therapy does not eliminate latent virus or prevent subsequent recurrences.
Acyclovir↗