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Biomedical subjects

G J Naylor

Publications and source records attributed to G J Naylor.

At least 19 recordsLinked to original sources
PubMed2001

A model for phylogenetic inference using structural and chemical covariates.

We investigated whether or not evolutionary change in DNA sequence data was homogeneous across different classes of base pairs. DNA sequences for eight protein-coding mitochrondrial genes were obtained for 38 vertebrate taxa from GenBank. Each nucleotide site in the alignment was classified according to a number of covariates, including its codon position, genetic code degeneracy, and hydrophobicity. The evolutionary transition matrix for each base was estimated by tracing implied character changes under parsimony on a known phylogenetic tree. Canonical variates analyses of the inferred transition matrices were performed for each gene to determine whether or not different classes of bases behaved similarly. We found five distinct clusters of transition matrices that could be roughly defined by combinations of codon position and degeneracy. This pattern was consistent among all genes. A stochastic model of rate variation based on the interaction of the covariates was developed to assess the statistical significance of the clusters. The five-group classification was found to explain significantly more sequence variation than did a codon only classification, a codon degeneracy classification, or a codon and degeneracy classification. The same five-group classification was found for all genes tested, suggesting a common process underlying the molecular evolution of the mitochondrial genome. These results confirm that there are classes of base pairs that evolve differently, and suggest that models of sequence evolution that incorporate covariate information may be useful in developing nucleotide substitution models that more accurately reflect evolutionary history.

Animals↗
PubMed2000

Measuring shifts in function and evolutionary opportunity using variability profiles: a case study of the globins.

Variability profiles measured over a set of aligned sequences can be used to estimate evolutionary freedom to vary. Differences in variability profiles between clades can be used to identify shifts in function at the molecular level. We demonstrate such a shift between the alpha and beta subunits of hemoglobin. We also show that the variability profiles for myoglobin are different between whales and primates and speculate that the differences between the two clades may reflect a shift associated with the novel oxygen storage demands in the lineage leading to whales. We discuss the relationship between sequence variability and "evolutionary opportunity" and explore the utility of Maynard Smith's multidimensional evolutionary opportunity space metaphor for exploring functional constraints, genetic redundancy, and the context dependency of the genotype-phenotype map. This work has implications for quantitatively defining and comparing protein function. Supplementary data is available from bioinfo.mbb.yale. edu/align.

Animals↗
PubMed1999

Phylogenetic inference from conserved sites alignments.

Molecular sequences provide a rich source of data for inferring the phylogenetic relationships among species. However, recent work indicates that even an accurate multiple alignment of a large sequence set may yield an incorrect phylogeny and that the quality of the phylogenetic tree improves when the input consists only of the highly conserved, motif regions of the alignment. This work introduces two methods of producing multiple alignments that include only the conserved regions of the initial alignment. The first method retains conserved motifs, whereas the second retains individual conserved sites in the initial alignment. Using parsimony analysis on a mitochondrial data set containing 19 species among which the phylogenetic relationships are widely accepted, both conserved alignment methods produce better phylogenetic trees than the complete alignment. Unlike any of the 19 inference methods used before to analyze this data, both methods produce trees that are completely consistent with the known phylogeny. The motif-based method employs far fewer alignment sites for comparable error rates. For a larger data set containing mitochondrial sequences from 39 species, the site-based method produces a phylogenetic tree that is largely consistent with known phylogenetic relationships and suggests several novel placements. J. Exp. Zool. ( Mol. Dev. Evol.) 285:128-139, 1999.

Amino Acid Sequence↗
PubMed1992

Rates of mitochondrial DNA evolution in sharks are slow compared with mammals.

The rate of mitochondrial DNA (mtDNA) evolution has been carefully calibrated only in primates. Similarity between the primate calibration and rates estimated for other vertebrates has led to widespread assumption of a constant molecular clock in vertebrates even though this has never been rigorously tested. We report here the examination of mtDNA sequence variation for 13 species of sharks from two orders that are well represented in the fossil record to test the constancy hypothesis. Nucleotide substitution rates in the cytochrome b and cytochrome oxidase I genes in sharks are seven- to eightfold slower than in primates or ungulates. This difference in substitution rate cannot be explained by nucleotide composition bias, codon-usage bias, selection, or choice of genes sequenced, and was confirmed by comparing species recently separated by the rise of the Isthmus of Panama. Such differences in mtDNA substitution rates among taxa indicate that it is inappropriate to use a calibration for one group to estimate divergence times or demographic parameters for another group. High-resolution studies of molecular evolutionary rates require taxon-specific calibrations.

Animals↗
PubMed1990

Tissue aluminum concentrations stability over time, relationship to age, and dietary intake.

Aluminum concentration was measured in serum, whole blood, hair, and urine by neutron activation analysis. Seventy-six nondemented subjects were investigated. Not all assays were done on all subjects (e.g., serum aluminum on 76 subjects, whole blood aluminum on 42 subjects), but tissue aluminum concentrations were estimated on more than one occasion on 32 subjects. The mean +/- SD aluminum concentration in serum was 0.219 +/- 0.063 micrograms/ml (N = 76), in whole blood 0.368 +/- 0.091 micrograms/ml (N = 42), in urine 0.092 +/- 0.076 micrograms/ml (N = 42), and in hair 6.42 +/- 2.22 micrograms/g (N = 42). Using product moment correlation coefficient there was no significant correlation between age and tissue aluminum concentrations, nor between dietary intake of aluminum and tissue aluminum. The tissue aluminum concentrations were not stable over time even when dietary intake was constant. Tissue aluminum concentrations were measured in 14 patients after 7 days of dietary control and repeated approximately 6 weeks later, again after 7 days of dietary control. There was no significant correlation between the two estimations in any tissue measured. These results suggest that raised tissue aluminum concentrations reported in Alzheimer's disease are not an exaggeration of a normal ageing process, are not likely to be simply secondary to increased dietary aluminum intake, and that Alzheimer's disease does not represent the chronic toxic effect of moderately raised aluminum levels at the upper end of the normal distribution.

Adult↗
PubMed1990

Incorporation of inositol into the phosphoinositides of lymphoblastoid cell lines established from bipolar manic-depressive patients.

Lymphoblastoid cell lines established from patients suffering from bipolar manic-depressive psychosis or from a control group have been used to study the metabolism of the polyphosphoinositides in these cells. Cells were incubated for up to 6 h in [3H]inositol and the extent of inositol incorporation into the mono-, di- and triphosphoinositides was measured after extracting the water- and lipid-soluble inositol-containing pools. Although both the uptake of inositol and the 'free' intracellular inositol pool sizes were similar in the two cell groups, the incorporation of [3H]inositol into the phosphoinositides of the cells derived from bipolar manic-depressives was significantly less (by around 50-60%) than that which occurred in the control cells.

Bipolar Disorder↗
PubMed1987

A controlled trial of methylene blue in severe depressive illness.

Methylene blue, 15 mg/day, was compared with placebo in treatment of severe depressive illness. The 3-week trial was designed to avoid bias by placebo response and also to avoid observer bias. Improvement in patients receiving methylene blue was significantly greater than in those receiving placebo. Methylene blue at a dose of 15 mg/day appears to be a potent antidepressant, and further clinical evaluation is essential.

Adult↗
PubMed1987

Further studies of vanadium in depressive psychosis.

Three studies are reported. In study 1, vanadium concentration was estimated by neutron activation analysis in hair, whole blood, serum and urine from 13 patients suffering from depressive psychosis and then when on recovery. Vanadium concentration of hair, whole blood and serum decreased significantly with recovery, but there was no significant change in 24-h urinary excretion or in renal clearance of vanadium. In study 2, vanadium concentration was estimated by neutron activation analysis in serum and urine of 31 patients with depressive psychosis and of 27 normal controls. Mean renal clearance of vanadium was significantly lower and mean serum vanadium concentration significantly higher in depressed patients than in controls. Mean 24-h excretion of vanadium did not differ between the two groups. Vanadium excretion did not correlate with urine volume, with serum concentration or with age. In study 3, erythrocyte Na-K ATPase activity and serum vanadium concentrations were estimated in 58 patients. There was a strong negative correlation between the two, supporting the suggestion that changes in tissue vanadium concentration may explain the changes in sodium transport which occur in depressive psychosis.

Adult↗
PubMed1986

A two-year double-blind crossover trial of the prophylactic effect of methylene blue in manic-depressive psychosis.

A 2-year prophylactic trial was carried out in 31 bipolar manic-depressive subjects, comparing 300 mg/day methylene blue on a double-blind crossover basis with 15 mg/day. All patients were also maintained on lithium. Seventeen patients completed the 2-year trial. During the year the patients were treated with methylene blue at 300 mg/day, they were significantly less depressed than during the year on 15 mg/day. No significant difference in the severity of manic symptoms was shown. The trial had obvious limitations, e.g., a small number of subjects, a relatively large number of dropouts, relatively simple rating scales, doubts about blindness, and uncertainty as to whether or not 15 mg methylene blue per day could be considered a placebo. However, the results suggest that methylene blue may be a useful addition to lithium in the long-term treatment of manic-depressive psychosis and warrants further investigation.

Bipolar Disorder↗