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J J Doyle

Publications and source records attributed to J J Doyle.

At least 37 records · Page 2Linked to original sources

Evolution of genes and taxa: a primer.

The rapidly growing fields of molecular evolution and systematics have much to offer to molecular biology, but like any field have their own repertoire of terms and concepts. Homology, for example, is a central theme in evolutionary biology whose definition is complex and often controversial. Homology extends to multigene families, where the distinction between orthology and paralogy is key. Nucleotide sequence alignment is also a homology issue, and is a key stage in any evolutionary analysis of sequence data. Models based on our understanding of the processes of nucleotide substitution are used both in the estimation of the number of evolutionary changes between aligned sequences and in phylogeny reconstruction from sequence data. The three common methods of phylogeny reconstruction--parsimony, distance and maximum likelihood--differ in their use of these models. All three face similar problems in finding optimal--and reliable--solutions among the vast number of possible trees. Moreover, even optimal trees for a given gene may not reflect the relationships of the organisms from which the gene was sampled. Knowledge of how genes evolve and at what rate is critical for understanding gene function across species or within gene families. The Neutral Theory of Molecular Evolution serves as the null model of molecular evolution and plays a central role in data analysis. Three areas in which the Neutral Theory plays a vital role are: interpreting ratios of nonsynonymous to synonymous nucleotide substitutions, assessing the reliability of molecular clocks, and providing a foundation for molecular population genetics.

Base Sequence↗

A pharmacoeconomic evaluation of two new products for the treatment of overactive bladder.

The objective of this study is to evaluate the cost effectiveness of two new treatments for overactive bladder: once-daily controlled-release oxybutynin, and twice-daily tolterodine, with a comparison with oxybutynin immediate release. Also estimated are the potential cost savings to a health plan budget resulting from increased utilization of the most cost-effective treatment. The design is a decision-tree model based on clinical trial data and expert panel estimates with a six-month time horizon conducted from a payer perspective. The primary outcome measure used in the analysis was treatment success, with success defined as zero incontinence episodes per week. A secondary outcome measure was the expected number of continent days. As first-line therapy, controlled-release oxybutynin is the most cost-effective treatment as measured by expected cost per success and expected cost per continent days. Controlled-release, once-daily oxybutynin yielded the highest expected success rate and the highest number of expected continent days. The expected cost of treatment with controlled-release oxybutynin was lower than tolterodine and equivalent to immediate-release oxybutynin. Increased utilization of controlled-release oxybutynin results in an estimated saving of $0.007 to $0.026 per member per month for a hypothetical HMO. The model was robust, incorporating all assumptions based on univariate and multivariate sensitivity analysis. Initiating treatment with controlled-release oxybutynin is the most cost-effective approach to treatment for overactive bladder.

Benzhydryl Compounds↗

Intracellular gene transfer in action: dual transcription and multiple silencings of nuclear and mitochondrial cox2 genes in legumes.

The respiratory gene cox2, normally present in the mitochondrion, was previously shown to have been functionally transferred to the nucleus during flowering plant evolution, possibly during the diversification of legumes. To search for novel intermediate stages in the process of intracellular gene transfer and to assess the evolutionary timing and frequency of cox2 transfer, activation, and inactivation, we examined nuclear and mitochondrial (mt) cox2 presence and expression in over 25 legume genera and mt cox2 presence in 392 genera. Transfer and activation of cox2 appear to have occurred during recent legume evolution, more recently than previously inferred. Many intermediate stages of the gene transfer process are represented by cox2 genes in the studied legumes. Nine legumes contain intact copies of both nuclear and mt cox2, although transcripts could not be detected for some of these genes. Both cox2 genes are transcribed in seven legumes that are phylogenetically interspersed with species displaying only nuclear or mt cox2 expression. Inactivation of cox2 in each genome has taken place multiple times and in a variety of ways, including loss of detectable transcripts or transcript editing and partial to complete gene loss. Phylogenetic evidence shows about the same number (3-5) of separate inactivations of nuclear and mt cox2, suggesting that there is no selective advantage for a mt vs. nuclear location of cox2 in plants. The current distribution of cox2 presence and expression between the nucleus and mitochondrion in the studied legumes is probably the result of chance mutations silencing either cox2 gene.

Cell Nucleus↗

Origins, colonization, and lineage recombination in a widespread perennial soybean polyploid complex.

Polyploidy is a dominant feature of flowering plant genomes, including those of many important crop species, implying that polyploidy confers evolutionary advantages on plant species. Recent molecular studies suggest that polyploids often originate many times from the same progenitor diploids. For this to provide a broader genetic base for a polyploid species, there must be lineage recombination in the genomes of polyploids having different origins, and this has rarely been documented in recently formed wild polyploid species. Glycine tabacina, a wild relative of soybean, forms a widespread polyploid complex in Australia and the islands of the Pacific Ocean. In a sample of 40 G. tabacina plants, DNA sequence variation at one homoeologous histone H3-D locus identified three alleles, each also found in Australian diploid Glycine species. These data agree with our previous studies of chloroplast DNA variation in suggesting that this polyploid has originated several times. Both the origins of the polyploid and several independent dispersals from Australia to oceanic islands appear to have occurred within the last 30,000 years. The distributions of histone alleles, chloroplast haplotypes, and alleles at two isozyme loci were uncorrelated, and 20 multilocus genotypes were found among the 40 plants sampled. Extensive lineage recombination is thus hypothesized in the polyploid, involving migration and occasional outcrossing in this predominantly inbreeding species. The combination of multiple origins with gene exchange among lineages increases the genetic base of a polyploid and may help explain the wide colonization of polyploid G. tabacina relative to its diploid progenitors.

Journal Article↗

Chloroplast-expressed glutamine synthetase (ncpGS): potential utility for phylogenetic studies with an example from Oxalis (Oxalidaceae).

Chloroplast-expressed glutamine synthetase (ncpGS), a nuclear-encoded gene containing several introns, is introduced as a tool for phylogenetic studies at lower taxonomic levels. This gene is a member of a multigene family, but it diverged long ago from the cytosolic-expressed members of the family and appears to be single copy in the majority of taxa examined to date. The conservation of both coding sequence and position of introns has allowed the design of primers for use in a broad range of dicot taxa to amplify and sequence a region of ncpGS that contains four introns. The utility of this region in phylogenetic studies of congeneric species is illustrated by an example using eight Oxalis species. The four introns in these taxa are typical in size (76 to 136 bp), base composition (high T content), and structure (e.g., sequence of splice sites and putative branch points) for plant internal introns. Levels of variation among these ncpGS sequences compare favorably with those of the internal transcribed spacer of nuclear ribosomal DNA (ITS) from the same taxa, and results of phylogenetic analysis of ncpGS data are generally congruent with previous results using ITS.

Base Sequence↗

Phylogeny, biogeography, and processes of molecular differentiation in Quercus subgenus Quercus (Fagaceae).

Quercus is one of the most abundant and economically important genera of woody plants in the Northern Hemisphere. To infer phylogenetic relationships within Quercus subgenus Quercus, chloroplast DNA (cpDNA) restriction sites and nucleotide sequences of the internal transcribed spacers (ITS) and the 5.8S coding region of the nuclear ribosomal DNA repeat were obtained for 44 individuals, including 25 species, intraspecific samples, and three outgroups. Separate parsimony analyses of each data set showed that individual gene trees were congruent and often complementary in supporting clades that generally corresponded to previously recognized taxonomic groups. Only one instance of strongly supported gene tree incongruence was detected and this anomalous pattern was explained best by ancient introgression of cpDNA across sectional boundaries. Simultaneous parsimony analysis of the pruned data sets supported the recognition of the strictly Eurasian section Cerris and resolved a novel hypothesis for the major infrageneric groups (Cerris- (Lobatae- (Protobalanus + Quercus sensu stricto))). The biogeographic hypothesis that all major oak lineages evolved locally at middle latitudes within the general distribution of their fossil ancestors was fully supported. This set of relationships also suggested a New World origin for the widespread white oaks of the Northern Hemisphere (section Quercus s. s.). For both data sets, inter- and intraspecific sampling within section Protobalanus showed little correspondence to morphological species. Greater cladistic structure among the samples was obtained by cpDNA restriction sites and two well-delimited plastomes types comprising a total of 15 distinct haplotypes were resolved. Haplotypes of 2 of the peripheral species in this species complex occupy terminal portions of one of the plastome clades, suggesting a more recent origin relative to those of more widespread species. The phylogeography of the two divergent plastome types suggested a north-south pattern, consistent with a Late Tertiary disjunction in the ancestral distribution of section Protobalanus.

Cell Nucleus↗

Potential phylogenetic utility of the low-copy nuclear gene pistillata in dicotyledonous plants: comparison to nrDNA ITS and trnL intron in Sphaerocardamum and other Brassicaceae.

We report the potential phylogenetic utility of DNA sequence data from the last 700 bp of a ca. 1-kb intron of the MADS-box gene pistillata from a sampling of Sphaerocardamum species and other Brassicaceae. These results are compared with nrDNA ITS and the chloroplast trnL intron for the same taxa to demonstrate the potential phylogenetic utility of this pistillata intron and to identify potential historically independent sequences for an ongoing study of relationships within Sphaerocardamum. Analyses of the DNA sequence data for Brassicaceae indicated that pairwise divergences and potentially informative characters were higher in the pistillata intron (0.6-30.8%, 284 characters) and ITS (0-24%, 94 characters) than in the chloroplast trnL intron (0-4.2%, 17 characters). A comparison of Sphaerocardamum sequences identified low divergences and numbers of informative characters for trnL intron (0-2.4%, 1 character) and nrDNA ITS (0-2.5%, 2 characters) and substantially more variation among the pistillata sequences (0.15-3.7%, 19 characters). Phylogenetic analyses of these pistillata sequences fully resolve ingroup relationships without character conflict. Results of pistillata PCR amplifications from a broader dicot sample showed that some primers may be useful in amplifying orthologous pistillata sequences. Ultimately this pistillata intron may be a valuable source of phylogenetic characters at lower taxonomic levels.

Arabidopsis Proteins↗

Comparison of extended-release venlafaxine, selective serotonin reuptake inhibitors, and tricyclic antidepressants in the treatment of depression: a meta-analysis of randomized controlled trials.

The purpose of this study was to summarize and compare the clinical success rates of extended-release venlafaxine, some selective serotonin reuptake inhibitors (SSRIs), and certain tricyclic antidepressants (TCAs). A meta-analytic approach was used to synthesize outcomes from published randomized controlled trials involving patients scoring > or =15 on the Hamilton Rating Scale for Depression (HAM-D) or > or =18 on the Montgomery-Asberg Depression Rating Scale (MADRS). Searches of the MEDLINE, EMBASE, and International Pharmaceutical Abstracts databases were performed, as were searches of references from retrieved articles and reviews. Drugs included in the comparison were extended-release venlafaxine (venlafaxine-XR); the SSRIs citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline; and the TCAs amitriptyline, imipramine, desipramine, and nortriptyline. Therapeutic success was defined as a 50% decrease in the HAM-D or MADRS score. Data were extracted by 2 independent evaluators, with differences resolved through consensus discussions. Weighted mean success rates were calculated for each drug class, using a random-effects model. The resulting data represent 44 trials with 63 study arms and 4033 patients with depression. Venlafaxine-XR demonstrated a 73.7% success rate, which was statistically significantly greater than that of the studied SSRIs (61.1%) and TCAs (57.9%) (P<0.001). Thus this meta-analysis of randomized controlled studies of patients with depression suggests that venlafaxine-XR is clinically superior in efficacy to SSRIs and TCAs. Venlafaxine-XR also had universally lower, though nonsignificant, dropout rates.

Antidepressive Agents, Second-Generation↗

Incongruence in the diploid B-genome species complex of Glycine (Leguminosae) revisited: histone H3-D alleles versus chloroplast haplotypes.

Variation at the single-copy nuclear locus histone H3-D was surveyed in the diploid B-genome group of Glycine subgenus Glycine (Leguminosae: Papilionoideae), which comprises three named Australian species and a number of distinct but as yet not formally recognized taxa. A total of 23 alleles was identified in the 44 accessions surveyed. Only one individual was clearly heterozygous, which is not surprising given the largely autogamous breeding system of subgenus Glycine. Alleles differed by as many as 19 nucleotide substitutions, nearly all in the three introns; length variation was minimal. Phylogenetic analysis identified two shortest allele trees with very little homoplasy, suggesting that recombination has been rare. Both topological and data set incongruence were statistically significant between histone H3-D allele trees and trees inferred from chloroplast DNA haplotypes previously described from these same accessions. Whereas the distribution of H3-D alleles agrees well with morphologically based taxonomic groupings, chloroplast DNA haplotype polymorphisms transgress species boundaries, suggesting that the chloroplast genome is not tracking taxic relationships. Divergences among chloroplast DNA haplotypes involved in such transgressive patterns appear to be more recent than speciation events, suggesting hybridization rather than lineage sorting.

Alleles↗

Pharmacoeconomic analysis of topical treatments for tinea infections.

BACKGROUND: A payor-perspective economic analysis of the topical creams ciclopirox, clotrimazole, ketoconazole, miconazole, and terbinafine (TER) used to treat dermatophytosis has been made. This pharmacoeconomic evaluation was conducted in Austria, Germany, and Switzerland. METHODS: A four-phase approach was used. Phase 1: experts were assembled to identify the standard approach for management of fungal infections and a decision tree was constructed to model the process. Phase 2: meta-analysis was used to determine success, failure, and relapse rates. Phase 3: economic analyses performed included cost of regimen, total expected cost, and cost-effectiveness. Phase 4: sensitivity analyses (robustness analysis) were also executed to determine the validity of the assumptions. RESULTS: In the total expected cost analysis, TER demonstrated the lowest overall cost of treating patients. Terbinafine also provided the highest number of disease-free days during the analytic time horizon and, consequently, the lowest cost per disease-free day. Sensitivity analyses suggest that TER is the most cost-effective topical product for treating dermatophytosis in Austria, Germany, and Switzerland. CONCLUSIONS: All analytic scenarios suggest that TER therapy demonstrates lower expected costs and generates more DFDs when compared with the fungistatic topical therapies included in this pharmacoeconomic analysis. Terbinafine is expected to be the most cost-effective choice in Austria, Germany, and Switzerland for treatment of dermatophytosis minor.

Administration, Topical↗

The role of erythropoietin in the anemia of prematurity.

Neonatal erythropoiesis is limited by a relatively inadequate production of erythropoietin. This is likely the result of dependence on the hepatic production of erythropoietin and an incomplete switchover to renal production. The present model of neonatal erythropoiesis suggests that the use of exogenous erythropoietin should correct the early anemia of prematurity that is observed at 6 weeks of age in premature newborns. Randomized, controlled trials of erythropoietin use in very low birthweight infants are reviewed. The data support the conclusion that erythropoietin at doses of > or = 750 u/kg/wk started at less than 7 days of age results in improved reticulocyte counts and hemoglobin levels, but does not reduce the number of infants who will be exposed to blood products. Erythropoietin at doses of > or = 600 u/kg/wk started at an average of 21 days of life improves reticulocyte counts and hemoglobin levels, and reduces the number of infants will will require late transfusion, but does nothing for the bulk of infants who are transfused before that age.

Anemia, Neonatal↗

Trees within trees: genes and species, molecules and morphology.

The construction and interpretation of gene trees is fundamental in molecular systematics. If the gene is defined in a historical (coalescent) sense, there can be multiple gene trees within the single contiguous set of nucleotides, and attempts to construct a single tree for such a sequence must deal with homoplasy created by conflict among divergent histories. On a larger scale, incongruence is expected among gene tree topologies at different loci of individuals within sexually reproducing species, and it has been suggested that this discordance can be used to delimit species. A practical concern for such topological methods is that polymorphisms may be maintained through numerous cladogenic events; this polymorphism problem is less of a concern for nontopological approaches to species delimitation using molecular data. Although a central theoretical concern in molecular systematics is discordance between a given gene tree and the true "species tree," the primary empirical problem faced in reconstructing taxic phylogeny is incongruence among the trees inferred from different sequences. Linkage relationships limit character independence and thus have important implications for handling multiple data sets in phylogenetic analysis, particularly at the species level, where incongruence among different historically associated loci is expected. Gene trees can also be reconstructed for loci that influence phenotypic characters, but there is at best a tenuous relationship between phenotypic homoplasy and homoplasy in such gene trees. Nevertheless, expression patterns and orthology relationships of genes involved in the expression of phenotypes can in theory provide criteria for homology assessment of morphological characters.

Anatomy, Comparative↗

Necessity of routine chest roentgenography after thoracentesis.

OBJECTIVE: To determine the necessity of posteroanterior chest roentgenography for the identification of pneumothorax and other complications after thoracentesis. DESIGN: Prospective cohort study. SETTING: Tertiary care teaching hospital. PATIENTS: 67 men and 43 women (mean age +/- SD, 62.4 +/- 13.2 years). Exclusion criteria included age younger than 18 years, concurrent pleural biopsy, ultrasound guidance, and use of mechanical ventilation. MEASUREMENTS: 174 thoracenteses done between March 1991 and June 1993. RESULTS: 2 hemothoraces (1.2%) occurred, and 8 patients had a total of 9 pneumothoraces (5.2%). The roentgenograms obtained immediately after the procedures identified 8 pneumothoraces; the other pneumothorax was seen incidentally on a delayed roentgenogram obtained 3 days later. Pneumothorax was suspected in 5 of the 8 cases, and tube thoracostomy was done in 4 of these 5 cases. Patients with unsuspected pneumothorax identified on the roentgenogram obtained immediately after the procedure did not receive treatment for their pneumothoraces. Univariate analysis showed that the variables that correlated significantly with pneumothorax were aspiration of air during the procedure (relative risk ratio, 12.3; 95% CI, 3.7 to 41.4), number of passes with the thoracentesis needle (relative risk ratio, 6.1; CI, 1.6 to 23.3), history of thoracic radiation therapy (relative risk ratio, 10.5; CI, 2.5 to 44.4), and operator suspicion of pneumothorax (relative risk ratio, 25.9; CI, 8.6 to 78.5). CONCLUSION: Among hospitalized patients with pleural effusions, we identified subgroup of patients in whom the risk for pneumothorax is low enough (approximately 1%) with sufficiently minimal clinical consequences to justify the avoidance of about 60% of chest roentgenograms obtained after thoracentesis. These patients are clinically stable, have not previously received chest irradiation, had only one pass at thoracentesis attempted without the aspiration of any air, and give no other indication of pneumothorax.

Aged↗

The distribution and phylogenetic significance of a 50-kb chloroplast DNA inversion in the flowering plant family Leguminosae.

Species in 9 of the approximately 650 genera of the flowering plant family Leguminosae are known to possess a large (50-kb) inversion in their chloroplast genomes, relative to the gene order found most commonly among land plants. Putatively basal elements of the family have not been surveyed for the inversion, which is unknown outside the legumes. Using a combination of polymerase chain reaction and restriction-mapping approaches employing primers or hybridization probes flanking inversion endpoints, 132 legume genera were screened for the presence of the inversion. The inversion was found to be absent in all taxa from two of the three subfamilies (Mimosoideae and Caesalpinioideae), whereas the inversion was found to be present in most taxa of the third subfamily (Papilionoideae). Two papilionoid tribes, Swartzieae and Sophoreae, were heterogeneous for the inversion, which is consistent with a number of lines of evidence suggesting the polyphyly of these tribes. The 50-kb inversion appears to be a unique event in the evolution of Leguminosae, providing a synapomorphy for a clade that includes most of the Papilionoideae.

Base Sequence↗

Phylogenetic utility of histone H3 intron sequences in the perennial relatives of soybean (Glycine: Leguminosae).

Histone H3 loci form a large multigene family in most plant species. In Glycine, some of these loci possess introns, whose sequences can provide characters for assessing phylogenetic relationships among species of the genus. Phylogenetic analyses of two closely related H3-B loci revealed a complex evolutionary pattern, producing trees from which species relationships could not be inferred readily. The single H3-D locus, in contrast, provided data suitable for the construction of gene trees whose topologies were sufficiently similar to other hypotheses of relationships within the subgenus Glycine to give confidence that evolution at this locus is tracking species phylogenies. H3-D topologies identified several of the same groupings found in previous phylogenetic studies using the chloroplast genome. However, histone H3-D and chloroplast genome data sets were in other respects incongruent, as revealed by both topological differences and numerical measures of congruence. The principal difference involved Glycine falcata, whose chloroplast genome belongs to one of the three strongly supported clades in the subgenus, but whose histone H3-D allele was sister to those of the remaining members of the subgenus. The H3-D topology is more in keeping with the morphologically, ecologically, and genetically divergent nature of this species. The H3-D locus appears to be a useful source of phylogenetic characters for interspecific studies in Glycine, providing resolution among taxa whose relationships were unresolved in previous studies.

Chloroplasts↗

Genepool variation in genus Glycine subgenus Soja revealed by polymorphic nuclear and chloroplast microsatellites.

A combination of nuclear and chloroplast simple sequence repeats (SSRs) have been used to investigate the levels and pattern of variability detected in Glycine max and G. soja genotypes. Based on the analysis of 700 soybean genotypes with 115 restriction fragment length polymorphism (RFLP) probes, 12 accessions were identified that represent 92% of the allelic variability detected in this genepool. These 12 core genotypes together with a sample of G. max and G. soja accessions were evaluated with 11 nuclear SSRs that detected 129 alleles. Compared with the other G. max and G. soja genotypes sampled, the core genotypes represent 40% of the allelic variability detected with SSRs. Despite the multi-allelic nature of soybean SSRs, dendrograms representing phenetic relationships between accessions clustered according to their subspecies origin. In addition to biparentally inherited nuclear SSRs, two uniparentally (maternally) transmitted chloroplast SSRs were also studied. A total of seven haplotypes were identified, and diversity indices of 0.405 +/- 0.088 and 0.159 +/- 0.071 were obtained for the two chloroplast SSRs. The availability of polymorphic SSR loci in the chloroplast genome provides new opportunities to investigate cytonuclear interactions in plants.

Cell Nucleus↗