Stem cell research.
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Biomedical Research↗
Biomedical subjects
R G Shaw
Publications and source records attributed to R G Shaw.
Constraint to adaptive evolution in response to global warming.
We characterized the genetic architecture of three populations of a native North American prairie plant in field conditions that simulate the warmer and more arid climates predicted by global climate models. Despite genetic variance for traits under selection, among-trait genetic correlations that are antagonistic to the direction of selection limit adaptive evolution within these populations. Predicted rates of evolutionary response are much slower than the predicted rate of climate change.
Adaptation, Physiological↗
Range shifts and adaptive responses to Quaternary climate change.
Tree taxa shifted latitude or elevation range in response to changes in Quaternary climate. Because many modern trees display adaptive differentiation in relation to latitude or elevation, it is likely that ancient trees were also so differentiated, with environmental sensitivities of populations throughout the range evolving in conjunction with migrations. Rapid climate changes challenge this process by imposing stronger selection and by distancing populations from environments to which they are adapted. The unprecedented rates of climate changes anticipated to occur in the future, coupled with land use changes that impede gene flow, can be expected to disrupt the interplay of adaptation and migration, likely affecting productivity and threatening the persistence of many species.
Adaptation, Physiological↗
Spontaneous mutational effects on reproductive traits of arabidopsis thaliana.
A study of spontaneous mutation in Arabidopsis thaliana was initiated from a single inbred Columbia founder; 120 lines were established and advanced 17 generations by single-seed descent. Here, we report an assay of reproductive traits in a random set of 40 lines from generations 8 and 17, grown together at the same time with plants representing generation 0. For three reproductive traits, mean number of seeds per fruit, number of fruits, and dry mass of the infructescence, the means did not differ significantly among generations. Nevertheless, by generation 17, significant divergence among lines was detected for each trait, indicating accumulation of mutations in some lines. Standardized measures of mutational variance accord with those obtained for other organisms. These findings suggest that the distribution of mutational effects for these traits is approximately symmetric, in contrast to the usual assumption that mutations have predominantly negative effects on traits directly related to fitness. Because distinct generations were grown contemporaneously, each line was represented by three sublines, and seeds were equal in age, these estimates are free of potentially substantial sources of bias. The finding of an approximately symmetric distribution of mutational effects invalidates the standard approach for inferring properties of spontaneous mutation and necessitates further development of more general approaches that avoid restrictions on the distribution of mutational effects.
Arabidopsis↗
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↗
Outbreeding depression varies among cohorts of Ipomopsis aggregata planted in nature.
Outbreeding depression in progeny fitness may arise from disruption of local adaptation, disruption of allelic coadaptation, or a combination of these "environmental" and "physiological" mechanisms. Thus the minimum spatial scale over which outbreeding depression arises should depend on the spatial scale of gene dispersal and (with an environmental mechanism) of change in selection regimes. We previously reported substantial outbreeding depression in lifetime fitness of progeny resulting from crosses among parents separated by 100 m in natural populations of the herbaceous plant Ipomopsis aggregata. In this paper we explore the effect of crossing distance on fitness in two additional experiments begun in 1987 and 1990. We planted seed progeny derived from partial diallel crossing designs in randomized blocks in maternal environments and scored emergence of seedlings, survival, and eventual flowering of individuals over the subsequent six to eight years. Nested within each diallel design were crossing distances of 1 m, 10 m, and 100 m. Compared to 1-m and 10-m progeny, 100-m progeny of the 1987 diallel suffered a significant reduction in seedling emergence, and both 1-m and 100-m progeny that survived to flower achieved lower lambda-values on average than 10-m progeny. Total outbreeding depression suffered by 100-m relative to 10-m progeny was approximately 10%, compared to approximately 30% in our earlier study of I. aggregata. Progeny of 10-m crosses also outperformed 1-m and 100-m progeny of the 1990 diallel by approximately 5%, but no difference among crossing distance treatments was significant. Thus, the magnitude of outbreeding depression in 100-m crosses varied among experiments. This is not surprising given likely spatial and temporal variation in gene flow and selection regimes, different population histories, and different parental and progeny environments. Characterizing outbreeding depression on the shortest spatial scales over which it is expressed, as well as its variation and causes, is worthwhile because it promises to shed light on the earliest stages of angiosperm speciation.
Breeding↗
Genetic components of variation in Nemophila menziesii undergoing inbreeding: morphology and flowering time.
The standard approaches to estimation of quantitative genetic parameters and prediction of response to selection on quantitative traits are based on theory derived for populations undergoing random mating. Many studies demonstrate, however, that mating systems in natural populations often involve inbreeding in various degrees (i.e. , self matings and matings between relatives). Here we apply theory developed for estimating quantitative genetic parameters for partially inbreeding populations to a population of Nemophila menziesii recently obtained from nature and experimentally inbred. Two measures of overall plant size and two of floral size expressed highly significant inbreeding depression. Of three dominance components of phenotypic variance that are defined under partial inbreeding, one was found to contribute significantly to phenotypic variance in flower size and flowering time, while the remaining two components contributed only negligibly to variation in each of the five traits considered. Computer simulations investigating selection response under the more complete genetic model for populations undergoing mixed mating indicate that, for parameter values estimated in this study, selection response can be substantially slowed relative to predictions for a random mating population. Moreover, inbreeding depression alone does not generally account for the reduction in selection response.
Asteraceae↗
Preventing endoscopic retrograde cholangiopancreatography related sepsis: a randomized controlled trial comparing two antibiotic regimes.
Current antibiotic prophylaxis for endoscopic retrograde cholangiopancreatography (ERCP) is not standardized and may be inadequate. We aimed to evaluate the efficacy of 3 days of additional oral antibiotics in the prevention of ERCP-related sepsis. One hundred and fifty-six patients were randomized prospectively to receive either intravenous ticarcillin and clavulinic acid (Timentin; SmithKline Beecham, Dandenong, Victoria, Australia), pre-ERCP (group I) or Timentin and 3 days of oral amoxycillin and clavulinic acid (Augmentin; SmithKline Beecham, Dandenong, Victoria, Australia), group II). Blood cultures were taken 30 min after the procedure. The occurrence of sepsis, defined as a temperature over 38 degrees C, occurring in the first 7 days was recorded and the risk factors for the development of sepsis were evaluated. Four patients had significant positive blood cultures despite the prior administration of Timentin. Sepsis occurred in 10% of group I patients, but only 3% of group II patients (relative risk 3.30; 95% confidence intervals 0.74-14.8). The performance of sphincterotomy and the presence of common bile duct stones were significant risk factors for the development of sepsis. We would recommend 3 days of additional oral Augmentin after a single dose of intravenous antibiotics in patients at increased risk of sepsis, which would include those with bile duct stones and/or those undergoing a therapeutic procedure.
Amoxicillin↗
Quantitative genetics of response to competitors in Nemophila menziesii: a field experiment.
Recent investigations of evolution in heterogeneous environments have begun to accommodate genetic and environmental complexity typical of natural populations. Theoretical studies demonstrate that evolution of polygenic characters depends heavily on the genetic interdependence of the expression of traits in the different environments in which selection occurs, but information concerning this issue is scarce. We conducted a field experiment to assess the genetic variability of the annual plant Nemophila menziesii in five biotic regimes differing in plant density and composition. Significant, though modest, additive genetic variance in plant size was expressed in particular treatments. Evidence of additive genetic tradeoffs between interspecific and intraspecific competitive performance was found, but this result was not consistent throughout the experiment. Two aspects of experimental design may tend to obscure genetically based tradeoffs across environments in many previously published experiments: (1) inability to isolate additive genetic from other sources of variation and (2) use of novel (e.g., laboratory) environments.
Analysis of Variance↗
Estimating polygenic models for multivariate data on large pedigrees.
We have developed algorithms for the likelihood estimation of additive genetic models for quantitative traits on large pedigrees. The approach uses the expectation L-maximization (EM) algorithm, but avoids intensive computation. In this paper, we focus on extensions of previous work to the case of multivariate data. We exemplify the approach by analyses of bivariate data on a four-generation, 949-member pedigree of the snail Lymnaea elodes, and on a three-generation pedigree of the guppy Poecilia reticulata containing about 400 individuals.
Algorithms↗
Ranitidine-associated recurrent acute pancreatitis.
Ranitidine is a safe, widely prescribed drug for the treatment of peptic ulcer disease and is rarely associated with serious adverse reactions. This report describes a patient who suffered three episodes of acute pancreatitis associated with ranitidine prescribed for duodenal ulcer disease. On each occasion the pancreatitis resolved after withdrawal of ranitidine and recurred upon re-exposure. Underlying biliary and pancreatic disease was excluded. There has been no recurrence of pancreatitis in the five years of follow-up since ranitidine was discontinued.
Acute Disease↗
Pedigree analysis for quantitative traits: variance components without matrix inversion.
Recent developments in the animal breeding literature facilitate estimation of the variance components in quantitative genetic models. However, computation remains intensive, and many of the procedures are restricted to specialized designs and models, unsuited to data arising from studies of natural populations. We develop algorithms that allow maximum likelihood estimation of variance components for data on arbitrary pedigree structures. The proposed methods can be implemented on microcomputers, since no intensive matrix computations or manipulations are involved. Although parts of our procedures have been previously presented, we unify these into an overall scheme whose intuitive justification clarifies the approach. Two examples are analyzed: one of data on a natural population of Salivia lyrata and the other of simulated data on an extended pedigree.
Algorithms↗
Pendelluft and mixing in a single bifurcation lung model during high-frequency oscillation.
A single bifurcation with an adjustable daughter branch compliance ratio (VR) was used to simultaneously study pendelluft and longitudinal mixing during flow oscillations at frequencies (f) of 1-15 Hz and amplitudes (VOp) of 25-150 ml/s. Mixing coefficients (Deff) were determined from the dispersion of a CO2 bolus centered at the bifurcation point, and pendelluft volume was computed as a fraction of mother branch tidal volume (PVF) using measurements of airflow in the daughter branches. Plotted against frequency, PVF was a bell-shaped curve insensitive to the value of VOp. When VR = 2, a PVF peak of 0.25 appeared at f = 3 Hz, and when VR = 5, a PVF peak of 0.75 appeared at f = 4 Hz. After normalization by control values at VR = 1, Deff curves were also bell shaped, insensitive to the value of VOp and with peaks appearing at the same frequencies as the PVF peaks. The normalized Deff peak values were 1.7 when VR = 2 and 4.0 when VR = 5. The similarities in the PVF and Deff curves imply a direct relationship between pendelluft and enhanced mixing.
Algorithms↗
Polypentapeptide of elastin: temperature dependence of ellipticity and correlation with elastomeric force.
Circular dichroism (CD) is used to follow the conformational changes that attend temperature dependent aggregation leading to the viscoelastic (coacervate) state of the polypentapeptide of elastin in water. Two concentrations are used, 2.3 mg/ml and 0.023 mg/ml. The former results in aggregates of a size that exhibit much particulate distortion of the CD spectra whereas the latter results in spectra that are relatively free of distortions. Given the CD spectra of the temperature dependent aggregation of the lower concentration, it is possible to show that the same conformational change is occurring at high concentration. The structure of the polypentapeptide is one of limited order below 20 degrees C which undergoes an inverse temperature transition to a conformation characterized by a regularly recurring beta-turn at 40 degrees C. The temperature profile for the conformational change is compared to the temperature dependence of elastomeric force of gamma-irradiation cross-linked polypentapeptide coacervate. The curves virtually superimpose. When there is little order, there is little elastomeric force and elastomeric force develops to a near maximal value as the repeating Type II beta-turn conformation develops. Not only is the elastomeric state non-random, the more nearly random state has very little elasticity. These results are the inverse of expectations based on the classical theory of rubber elasticity.
Amino Acid Sequence↗
Infrared spectra of the Gramicidin A transmembrane channel: the single-stranded-beta 6-helix.
IR spectra are reported for preparations of Gramicidin A and malonyl Gramicidin A incorporated as the channel state in phospholipid structures. In this preparation Gramicidin A has already been shown to be unequivocally in the single-stranded beta-helical conformation. The result is an amide I frequency of 1633 +/- 1 cm-1. This demonstrates that the single-stranded beta-helix has an amide I frequency that has previously been considered to be diagnostic of antiparallel double-stranded beta-helix and of beta-sheet structures.
Gramicidin↗
Effects of cimetidine and ranitidine on hepatic drug metabolism.
Cimetidine has been shown to impair elimination of a number of drugs metabolized by the hepatic mixed-function oxidase enzymes. It is uncertain whether this is related to its histamine H2-receptor antagonism or to its intrinsic structure. Ranitidine is a more potent H2-receptor antagonist and has a completely different structure. Cimetidine (1 gm/day for 7 days) induced a 23% and 35% fall in mean systemic clearance of antipyrine and theophylline, whereas ranitidine (300 mg/day 7 days) had no significant effect on the clearance of either drug. Our data suggest that the inhibition of drug metabolism by cimetidine is not related to histamine H2-receptor antagonism.
Adult↗
Influence of smoking on healing rate of duodenal ulcer in response to cimetidine or high-dose antacid.
Fifty consecutive patients with symptomatic endoscopically proven duodenal ulcer were randomized double-blind to Mylanta II or cimetidine treatment schedules. Smoking habits were noted, but patients were not advised to alter these. Healing was determined by reendoscopy at 6 wk. Eighty percent of patients on active cimetidine and 52% on active Mylanta II had healed at 6 wk (not significantly); 85% of nonsmokers healed compared to 44% of smokers (p less than 0.03). In smokers, cimetidine achieved healing in 50%, Mylanta II in 39% (not significantly); while in nonsmokers, cimetidine achieved healing in 100%, Mylanta II in 67% (not significantly). These results indicate a significant and equally adverse effect of smoking on the healing rate of duodenal ulcer achieved by either cimetidine or Mylanta II.
Adolescent↗
Cardiac arrest after intravenous injection of cimetidine.
Three episodes, in which patients suffered a cardiac arrest in close association with receiving a bolus intravenous injection of cimetidine, are reported. The possible role of cimetidine in causing cardiac arrest, and the mechanisms which may be involved, are discussed. It is recommended that intravenous administration of cimetidine should be an infusion performed over at least 30 minutes.
Adult↗