Biomedical subjects

S J Baird

Publications and source records attributed to S J Baird.

8 recordsLinked to original sources

PubMed2001

Reproductive and developmental risks from ethylene oxide: a probabilistic characterization of possible regulatory thresholds.

Ethylene oxide is a gas produced in large quantities in the United States that is used primarily as a chemical intermediate in the production of ethylene glycol, propylene glycol, non-ionic surfactants, ethanolamines, glycol ethers, and other chemicals. It has been well established that ethylene oxide can induce cancer, genetic, reproductive and developmental, and acute health effects in animals. The U.S. Environmental Protection Agency is currently developing both a cancer potency factor and a reference concentration (RfC) for ethylene oxide. This study used the rich database on the reproductive and developmental effects of ethylene oxide to develop a probabilistic characterization of possible regulatory thresholds for ethylene oxide. This analysis was based on the standard regulatory approach for noncancer risk assessment, but involved several innovative elements, such as: (1) the use of advanced statistical methods to account for correlations in developmental outcomes among littermates and allow for simultaneous control of covariates (such as litter size); (2) the application of a probabilistic approach for characterizing the uncertainty in extrapolating the animal results to humans; and (3) the use of a quantitative approach to account for the variation in heterogeneity among the human population. This article presents several classes of results, including: (1) probabilistic characterizations of ED10s for two quantal reproductive outcomes-resorption and fetal death, (2) probabilistic characterizations of one developmental outcome-the dose expected to yield a 5% reduction in fetal (or pup) weight, (3) estimates of the RfCs that would result from using these values in the standard regulatory approach for noncancer risk assessment, and (4) a probabilistic characterization of the level of ethylene oxide exposure that would be expected to yield a 1/1,000 increase in the risk of reproductive or developmental outcomes in exposed human populations.

Animals↗

PubMed2001

Spatial structure and habitat variation in a grasshopper hybrid zone.

A hybrid zone between the grasshoppers Chorthippus brunneus and C. jacobsi (Orthoptera: Acrididae) in northern Spain has been analyzed for variation in morphology and ecology. These species are readily distinguished by the number of stridulatory pegs on the hind femur. Both sexes are fully winged and inhabit disturbed habitats throughout the study area. We develop a maximum-likelihood approach to fitting a two-dimensional cline to geographical variation in quantitative traits and for estimating associations of population mean with local habitat. This method reveals a cline in peg number approximately 30 km south of the Picos de Europa Mountains that shows substantial deviations in population mean compared with the expectations of simple tension zone models. The inclusion of variation in local vegetation in the model explains a significant proportion of the residual variation in peg number, indicating that habitat-genotype associations contribute to the observed spatial pattern. However, this association is weak, and a number of populations continue to show strong deviations in mean even after habitat is included in the final model. These outliers may be the result of long-distance colonization of sites distant from the cline center or may be due to a patchy pattern of initial contact during postglacial expansion. As well as contrasting with the smooth hybrid zones described for Chorthippus parallelus, this situation also contrasts with the mosaic hybrid zones observed in Gryllus crickets and in parts of the hybrid zone between Bombina toad species, where habitat-genotype associations account for substantial amounts of among-site variation.

Animals↗

PubMed2000

Hybridization, introgression, and linkage evolution.

Genetic mapping methods provide a unique opportunity to study the interactions of differentiated genes and genomes in a hybrid genetic background. After a brief discussion of theoretical and analytical concerns, we review the application of these methods to a wide range of evolutionary issues. Map-based studies of experimental hybrids indicate that most postzygotic reproductive barriers in plants are polygenic and that the expression of extreme or novel traits in segregating hybrids (transgressive segregation) results from the complementary action of divergent parental alleles. However, genetic studies of hybrid vigor do not concur in their interpretations of the relative roles of dominance, overdominance, and epistasis. Map-based studies of natural hybrids are much rarer, but the few existing studies confirm the polygenic basis of postzygotic barriers and demonstrate the utility of genetic linkage for detecting cryptic introgression. In addition, studies of experimental and natural hybrid lineages provide compelling evidence that homoploid hybrid speciation has occurred in nature, and that it represents a rapid and repeatable mode of speciation. Data further indicate that this mode is facilitated by strong fertility selection and high chromosomal mutation rates. We recommend that future studies of hybrid genomes focus on natural hybrids, not only because of the paucity of data in this area, but also because of the availability of highly recombinant hybrid genotypes in hybrid zones. Of particular value will be studies of long-lived or difficult-to-propagate organisms, which previously have not been amenable to genetic study.

Crosses, Genetic↗

PubMed1999

A comparison of multilocus clines maintained by environmental adaptation or by selection against hybrids.

There has recently been considerable debate over the relative importance of selection against hybrids ("endogenous" selection) vs. adaptation to different environments ("exogenous") in maintaining stable hybrid zones and hence in speciation. Single-locus models of endogenous and exogenous viability selection generate clines of similar shape, but the comparison has not been extended to multilocus systems, which are both quantitatively and qualitatively very different from the single-locus case. Here we develop an analytical multilocus model of differential adaptation across an environmental transition and compare it to previous heterozygote disadvantage models. We show that the shape of clines generated by exogenous selection is indistinguishable from that generated by endogenous selection. A stochastic simulation model is used to test the robustness of the analytical description to the effects of drift and strong selection, and confirms the prediction that pairwise linkage disequilibria are predominantly generated by migration. However, although analytical predictions for the width of clines maintained by heterozygote disadvantage fit well with the simulation results, those for environmental adaptation are consistently too narrow; reasons for the discrepancy are discussed. There is a smooth transition between a system in which a set of loci effectively act independently of each other and one in which they act as a single nonrecombining unit.

Adaptation, Physiological↗

PubMed1998

Rapid hybrid speciation in wild sunflowers.

Hybrid or "recombinational" speciation refers to the origin of a new homoploid species via hybridization between chromosomally or genetically divergent parental species. Theory predicts that this mode of speciation is punctuated, but there has been little empirical evidence to support this claim. Here, we test the hypothesis of rapid hybrid speciation by estimating the sizes of parental species chromosomal blocks in Helianthus anomalus, a wild sunflower species derived via hybridization between H. annuus and H. petiolaris. Analysis of the frequency spectrum of parental species chromosomal blocks with respect to predictions based on R. A. Fisher's [Fisher, R. A. (1953) Heredity 8, 187-197] junctions approach, suggests that H. anomalus arose rapidly, probably in fewer than 60 generations. This result is corroborated by independent lines of evidence demonstrating (i) a significant concordance between the genomes of H. anomalus and early generation H. annuus x H. petiolaris synthetic hybrids, and (ii) a rapid recovery of pollen fertility in these synthetic hybrid lineages. These results are not only consistent with theory but also provide a new and general method for estimating the tempo of hybrid speciation and dating the origin of hybrid zones.

Biological Evolution↗

PubMed1997

Evaluation of effect profiles: Functional Observational Battery outcomes.

The Functional Observational Battery (FOB) is a neurotoxicity screening assay composed of 25-30 descriptive, scalar, binary, and continuous endpoints. These outcomes have been grouped into six biologically logical domains as a means to interpret the neuroactive properties of tested chemicals (V. C. Moser, 1992, J. Am. Coll. Toxicol. 10(6), 661-669). However, no data-based exploration of these functional domains has been done. We investigated the degree to which experimental data correspond to the domain groupings by examining severity scores from 10 chemicals tested using a standardized protocol for acute exposure (V. C. Moser et al., 1995, J. Toxicol. Environ. Health 45, 173-210) and identifying endpoint groupings (factors) that best describe the interrelationships in the data, allowing a statistical assessment of whether the FOB endpoints break into domains. We also used a standard measure of bivariate association to confirm the results of the factor analysis. Our results show that while there are clear relationships among variables that compose some domains, there is often substantial correlation among endpoints in different domains. In addition, we investigated a related issue concerning the relative power of the chosen endpoint groupings for identifying significant domain effects. Results from a randomization analysis of the 10 chemicals suggest that the neurophysiologic domain structuring may provide some degree of statistical efficiency for identifying effects.

Animals↗

PubMed1989

An investigation of the transverse topology of bilirubin UDP-glucuronosyltransferase in rat hepatic endoplasmic reticulum.

Bilirubin UDP-glucuronosyltransferase (UDPGT) activity in sealed hepatic microsomes from clofibrate-treated rats was highly latent and was fully expressed by disruption of vesicles with detergents. Antibodies raised against purified bilirubin UDPGT were used to study the transmembrane orientation of the protein to provide a molecular understanding of the UDPGT latency. Immunoblot analysis of sealed microsomes, and microsomes after treatment with proteinases, showed that only a small portion of the protein resides on the cytoplasmic side of the microsomal vesicles. Treatment of microsomes with sodium deoxycholate allowed subtilisin and proteinase K to cleave the transferase, causing loss of activity and the release of smaller immunodetectable peptides. Treatment of the purified bilirubin UDPGT with peptide N-glycosidase F indicated that the enzyme was a glycoprotein. A working model of the transmembrane topology of bilirubin UDPGT is described.

Animals↗

PubMed1987

Use of Fab anti-IgG in phenotyping IgG-sensitised red cells.

Previously described methods of phenotyping red cells sensitised with IgG using the indirect antiglobulin test required the dissociation of the coating protein. Based on an entirely different principle, Fab fragments of anti-human IgG (Fab anti-IgG) were used to block the antiglobulin binding sites on cell-bound IgG molecules, removing the necessity to dissociate them from the red cell. Fab anti-IgG was found to be effective in blocking interfering IgG on in vivo and in vitro IgG-sensitised red cells, permitting successful red cell phenotyping. Strongly IgG-sensitised samples which could not be fully neutralised by chloroquine diphosphate (CDP) or blocked with Fab anti-IgG alone could usually be phenotyped using a combination of both these methods. This new procedure may be of use in immunohaematology laboratories.

Antibodies, Anti-Idiotypic↗