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PubMed2001

A comparative study of embryonic development of Japanese quail selected for different patterns of postnatal growth.

Patterns of early embryonic development have traditionally been viewed as invariant within vertebrate taxa. It has been argued that the specific differences which are found arise during the later stages of development. These differences may be a result of allometry, heterochrony or changes in relative growth rates. To test whether early embryonic development is indeed invariant, or whether selection of adult characteristics can alter embryonic growth, we compared embryonic development in birds selected for different patterns of postnatal growth. Using quail lines selected for high and low body mass, we compared somite formation, and muscle and feather development. We obtained data that showed changes in the rate of myotome formation in the brachial somites which contribute to muscle formation in the limbs and thorax. We think these observations are connected with intraspecific changes in adult morphology, ie., breast muscle size. Our findings suggest that selection for late ontogenetic/adult stages affects early embryonic development.

Journal Article↗
PubMed2003

Feeding in flow extremes: dependence of cirrus form on wave-exposure in four barnacle species.

Wave-exposure influences the form of many organisms. Curiously, the impact of flow extremes on feeding structures has received little attention. Barnacles extend feather-like legs to feed, and prior work revealed a highly precise association between leg length and water velocity in one species. To assess the generality of this flow-dependence, we quantified variation in four leg traits (ramus length, ramus diameter, seta length, and intersetal spacing) in four intertidal barnacles (Balanus glandula, Chthamalus dalli, Semibalanus cariosus, Pollicipes polymerus) over a wave-exposure gradient in the North-Eastern Pacific. All species exhibited a negative allometric relation between leg length and body mass. Proportionally longer feeding legs may permit smaller barnacles to avoid lower flow and particle flux associated with boundary layers. Although coefficients of allometry did not vary with wave-exposure, form differences among wave-exposures were substantial. Depending on the species, acorn barnacles of the same size from protected shores had feeding legs that were 37-80% longer and 18-25% thinner, and setae that were 36-50% longer and up to 25% more closely spaced, than those from exposed shores. Differences were less pronounced for the gooseneck barnacle, P. polymerus. Moreover, in situ water velocity explained an impressive percentage of overall leg-length variation: 92% in B. glandula, 67% in C. dalli, 91% in S. cariosus, and 92% in P. polymerus. Clearly, both size and shape of barnacle feeding legs respond to local flow conditions. This response appears widespread--across two orders of thoracican barnacles, Pedunculata and Sessilia, and two superfamilies of acorn barnacles (Balanoidea and Chthamaloidea)--and likely adaptive. Longer rami and setae would yield a larger feeding area in low flow, whereas shorter, stouter rami with shorter setae would be less vulnerable to damage in high flow. Finally, the proportionally most variable species was abundant in the widest range of habitats, suggesting that increased plasticity may permit a wider niche breadth.

Journal Article↗
PubMed2001

Growth curve analyses in selected duck lines.

1. Growth patterns of male ducks from 4 lines (lines A, B, C and D) selected for market weight were analysed and compared to growth patterns of ducks in the respective line 7 generations earlier. Growth curves were analysed using procedures derived from the Weibull sigmoidal function and the linear-linear relative growth rate model and simple allometry. 2. The ducks were fed ad libitum under 24-h lighting throughout the experiment. At weekly intervals from the time of hatch through 70 d of age, 16 ducks from each line were killed to determine body, carcase, breast-muscle, leg and thigh-muscle, and abdominal fat weights. 3. Line A was the heaviest line, followed by line B, line C and line D. However, body weight, carcase weight and breast-muscle weight at 49 d of age were not significantly different between lines A and B. After 7 generations of selection, the breast-muscle yield was increased to >19% and the abdominal fat percent was reduced to <1.4% in all lines. 4. The Weibull growth curve analysis of body weight showed an increase in the asymptotes during selection, while the age of the inflection point remained constant in all lines (21.3 to 26.0 d). For breast-muscle growth, ducks reached the inflection point 12.8 to 14.3 d later than for body weight. Between line A and line B, asymptotes for body weight, asymptotes for breast-muscle weight and allometric growth coefficients of breast muscle and leg and thigh muscles from 14 to 49 d were not significantly different. 5. The relative growth rate model discriminated body and breast-muscle growth patterns of line A and line B. The initial decline in the relative body growth rate was less and the time to reach the transition was longer in line A than line B. On the other hand, the initial decline in the relative breast-muscle growth rate was greater in line A than line B.

Abdomen↗
PubMed2004

Posthatch growth of the digestive system in wild and domesticated ducks.

1. Our study was designed to test the hypothesis that domestication and artificial selection have influenced the posthatch growth and functioning of the gastrointestinal (GI) tract of ducks. The mass and length of the GI tract organs, the growth of intestinal villi, the intestinal surface area and the activities of brush border digestive enzymes were measured in a commercial strain of Pekin duck and its wild ancestor, the mallard (Anas platyrhynchos), at regular intervals between hatch and 16 weeks of age. 2. The growth of the digestive organs, with respect to body mass, was described using allometry. Allometric mass exponents were then used to calculate body 'mass-corrected', or 'relative' organ masses, relative surface areas and relative enzyme activities. There were appreciable differences between data presented on a mass-specific (g/kg) and a mass-corrected (g/kg(b)) basis, which highlighted the importance of correcting for the complete effects of body mass when comparing the growth and function of the digestive system between strains. 3. While the process of domestication has induced major changes in the absolute characteristics of the GI tract, it has failed to have the same effect on the relative characteristics. During the first 2 weeks posthatch, the relative masses of the majority of digestive organs, and the GI tract as a whole, were the same in both strains. During weeks 3 to 5, domesticated ducks maintained higher absolute growth rates of the body and the GI tract, with the support of relatively smaller digestive organs. The relative masses of the small intestine and the GI tract as a whole were 45 and 66% higher respectively in mallards than in Pekin ducks during this period. 4. Domesticated ducks had elevated digestive enzyme activity and a greater absorptive surface area than mallards throughout development, both in absolute and relative terms. This appears to compensate for the failure of the relative masses of digestive organs in domesticated ducks to accompany the increased body mass and growth rate. 5. At 5 weeks posthatch, the absolute mass of the small intestine in domesticated ducks declined by 38%. There is no obvious explanation for this decline because the masses of other digestive organs, daily feed intake and body mass continued to rise.

Aging↗
PubMed2002

SB-242235, a selective inhibitor of p38 mitogen-activated protein kinase. II: in vitro and in vivo metabolism studies and pharmacokinetic extrapolation to man.

1. Inhibition of p38 MAP kinase has been investigated extensively as a potential therapy for cytokine-mediated diseases such as autoimmune and inflammatory diseases. SB-242235 (1-(4-piperidinyl)-4-(4-fluorophenyl)-5-(2-methoxy-4-pyrimidinyl) imidazole) is a potent and selective p38 MAP kinase inhibitor; the preclinical pharmacokinetics of SB-242235 have been described previously. The present studies were conducted to describe the in vitro metabolic rates and routes of SB-242235 metabolism, to characterize its in vivo preclinical metabolism, and to use these data to aid in the prediction of the pharmacokinetic behaviour of SB-242235 in man. 2. SB-242235 was metabolically stable in rat, dog, monkey and human hepatic microsomes, isolated hepatocytes and liver slices in vitro. The in vivo preclinical metabolism studies were consistent with the in vitro findings; SB-242235 was minimally metabolized, and was primarily excreted unchanged in the urine (45 and 67% of the administered dose in the rat and monkey, respectively). 3. Allometric scaling using various correction factors predicted that SB-242235 would have low clearance in man with a predicted half-life ranging from 11.5 to 18.7h. This prediction was consistent with the observed mean half-life of 16.4h in the first-in-man study for SB-242235. An allometric scaling method with a correction for interspecies differences in glomerular filtration rate provided the most accurate prediction of the pharmacokinetic behaviour of SB-242235 in humans, although the clinical data also highlight potential difficulties in conducting prospective allometry.

Animals↗
PubMed2006

Prediction of metabolic drug clearance in humans: in vitro-in vivo extrapolation vs allometric scaling.

Previously in vitro-in vivo extrapolation (IVIVE) with the Simcyp Clearance and Interaction Simulator has been used to predict the clearance of 15 clinically used drugs in humans. The criteria for the selection of the drugs were that they are used as probes for the activity of specific cytochromes P450 (CYPs) or have a single CYP isoform as the major or sole contributor to their metabolism and that they do not exhibit non-linear kinetics in vivo. Where data were available for the clearance of the drugs in at least three animal species, the predictions from IVIVE have now been compared with those based on allometric scaling (AS). Adequate data were available for estimating oral clearance (CLp.o.) in 9 cases (alprazolam, sildenafil, caffeine, clozapine, cyclosporine, dextromethorphan, midazolam, omeprazole and tolbutamide) and intravenous clearance in 6 cases (CLi.v.) (cyclosporine, diclofenac, midazolam, omeprazole, theophylline and tolterodine). AS predictions were based on five different methods: (1) simple allometry (clearance versus body weight); (2) correction for maximum life-span potential (CL x MLP); (3) correction for brain weight (CL x BrW); (4) the use of body surface area; and (5) the rule of exponents. A prediction accuracy was indicated by mean-fold error and the Pearson product moment correlation coefficient. Predictions were considered successful if the mean-fold error was <or=2. IVIVE predictions were accurate in 14 of 15 cases (mean-fold error range: 1.02-4.00). All five AS methods were accurate in 13, 11, 10, 10 and 14 cases, respectively. However, in some cases the error of AS exceeded fivefold. On the basis of the current results, IVIVE is more reliable than AS in predicting human clearance values for drugs mainly metabolized by CYP450 enzymes. This suggests that the place of AS methods in pre-clinical drug development warrants further scrutiny.

Animals↗
PubMed2006

Pharmacokinetics of muraglitazar (BMS-298585), a dual peroxisome proliferator-activated receptors (PPAR) alpha and gamma activator, in mice, rats, dogs, and monkeys.

The pharmacokinetic parameters of muraglitazar, a novel dual-activator of the peroxisome proliferator-activated receptors (PPAR) alpha and gamma, were determined in mice, rats, dogs, and monkeys after intravenous and oral administration. In the mouse, rat, and monkey the absolute oral bioavailability of muraglitazar ranged from 64 to 88%, and in the dog oral bioavailability was approximately 18%. The systemic clearance values of muraglitazar in the mouse, rat, dog, and cynomolgus monkey were 1.2, 3.0, 12.3 and 1.2 ml min-1 kg-1, respectively. The terminal elimination half-life was 2.4 h in dogs and 7.3 h in rats. The terminal elimination half-life could not be determined in the mouse and monkey because the sampling interval did not adequately cover the terminal elimination phase. Muraglitazar appears to be distributed outside of the vasculature, with the steady-state volume of distribution being approximately twofold that of the vascular volume in rats and dogs, and approximately twofold that of the total body water in mice. The systemic plasma clearance of muraglitazar in humans was predicted to be approximately 12-14 ml min-1 kg-1 based on allometry or by scaling of in vitro clearance parameters. Overall, the pharmacokinetic parameters of muraglitazar in preclinical species were acceptable for the advancement of the compound as a clinical candidate.

Administration, Oral↗
PubMedDate not supplied

Allometric relationship between body size and peak VO2 relative to age at menarche.

The present study examined allometric coefficients relating peak VO2 and body size relative to the time of menarche. Peak oxygen uptake (peak VO2) during exercise on a bicycle ergometer, stature and body mass were measured at annual intervals in a mixed-longitudinal sample of 40 active girls from 11 to 14 years of age. The girls were interviewed about their menarcheal status at each examination. The data were treated relative to the time before and after menarche: 2 years before (n = 18), 1 year before (n = 26), during the year of menarche (+/- 6 months, n = 32), 1 year after (n = 35) and 2 years after menarche (n = 22). Allometric coefficients were calculated for each of the five menarcheal groups based on logarithmic transformations of peak VO2 and body mass and peak VO2 and stature. The major axis of VO2 and body mass or stature (log transformed) was also calculated. This is the most appropriate slope for comparison with theoretical allometry coefficients. Mean peak VO2 increases from 2.1 +/- 0.19 L 2 years before menarche to 2.3 +/- 0.26 L 2 years after menarche. The slope of the major axis for body mass is always higher (0.508-0.926) than that for the allometric coefficient (0.323-0.591) in each of the menarcheal groups. The major axis slope and allometric coefficient are lowest between body mass and peak VO2 during the year of menarche. The slope of the major axis is below the theoretical allometric coefficients assuming geometric or elastic similarity, 2/3 or 3/4, before and at menarche and increases after menarche. Although the differences are not statistically significant, the results suggest that the relationship between body mass and peak VO2 at menarche is lower compared with relationships before and after this maturational landmark. Allometric coefficients for stature relative to peak VO2 show a similar pattern.

Adolescent↗
PubMedDate not supplied

Association of weights of some organs during the prenatal period.

The change of proportion of organ weights for the liver, intestines, lung, kidney, thymus, heart and spleen were analysed for 33 Japanese fetuses (sexes combined) by multivariate allometry. The thymus showed the highest allometric coefficient, and the spleen the next highest. The intestines, heart, liver, kidney showed medium coefficients, and the lung had the lowest.

Body Weight↗
PubMed2004

Disposition of a novel and potent alpha(v)beta3 antagonist in animals, and extrapolation to man.

1. The disposition of 3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl) propyl]-imidazolidin-1-yl]-3(S)-(6-methoxy-pyridin-3-yl)propionic acid (compound A), a potent and selective alpha(v)beta(3) antagonist, was characterized in several animal species in support of its selection for preclinical safety studies and potential clinical development. 2. Compound A exhibited marked species differences in pharmacokinetics; the plasma clearances and bioavailabilities ranged from 33-47 ml min(-1) kg(-1) in rats and mice to 4-9 ml min(-1) kg(-1) in dogs and monkeys, and about 20% in rats to 70-80% in dogs and monkeys, respectively. Both the intravenous (i.v.) and oral kinetics of compound A were linear over the dose range studied in dogs (0.1-5 mg kg(-1) i.v. and 0.25-20 mg kg(-1) orally [p.o.]) and rats (1-30 mg kg(-1) i.v. and 4-160 mg kg(-1) p.o.). 3. Compound A was eliminated substantially by urinary excretion; the urinary recovery of the unchanged drug was 67% in rhesus, 48% in dogs and about 30% in rats. In these animal species, biotransformation was modest. 4. Following i.v. administration of [(14)C]-compound A to rats, the radioactivity rapidly distributed to all tissues investigated, with high levels of the radioactivity detected in liver, kidney and intestine soon after the drug administration. The radioactivity declined rapidly, with less than 1% of the i.v. dose remaining at 30-h post-dose. 5. Compound A was moderately bound to plasma proteins, with unbound fractions of 26, 20, 14 and 5% for rats, dogs, monkeys and humans, respectively. It was bound primarily to human alpha(1)-acid glycoprotein (about 85% binding at 0.1% concentration), as compared with human albumin (< 50% binding at 4% concentration). 6. Using simple allometry, compound A was predicted to exhibit relatively low clearance (1-3 ml min(-1) kg(-1)) and low volume of distribution (0.1-0.3 l kg(-1)) in humans. Based on the predicted values, compound A was projected to exhibit a favourable oral pharmacokinetic profile in humans, with good bioavailability (50-80%). These predicted values provided a basis for compound selection for further development.

Administration, Oral↗
PubMed2000

Vertebrate Secondary Sexual Characteristics-Physiological Mechanisms and Evolutionary Patterns.

As most commonly presented, the organization-activation theory of sexual differentiation emphasizes the importance of the relative age of the organism for understanding steroid hormone effects. However, considering the actual physiological mechanisms of tissue enlargement (hyperplasia/hypertrophy) provides an additional perspective for interpreting patterns of evolutionary change in sexual dimorphism. Using that focus, it is possible to suggest mechanistic explanations for patterns of allometry and the size of some secondary sexual characteristics produced by "runaway" selection. It can also lead to the formulation of testable hypotheses regarding the type of sexually dimorphic characters that might evolve through "good genes" models; the relationship between intrasexual competition, polygyny, and the development and size of male weapons; and the control and type of secondary sexual characteristics that will be present in males with associated and disassociated reproductive patterns.

Journal Article↗
PubMedDate not supplied

Scaling of respiratory variables and the breathing pattern in birds: an allometric and phylogenetic approach.

Allometric equations can be useful in comparative physiology in a number of ways, not the least of which include assessing whether a particular species deviates from the norm for its size and phylogenetic group with respect to some specific physiological process or determining how differences in design among groups may be reflected in differences in function. The allometric equations for respiratory variables in birds were developed 30 yr ago by Lasiewski and Calder and presented as "preliminary" because they were based on a small number of species. With the expanded data base now available to reconstruct these allometries and the call for taking account of the nonindependence of species in this process through a phylogenetically independent contrasts (PIC) approach, we have developed new allometric equations for respiratory variables in birds using both the traditional and PIC approaches. On the whole, the new equations agree with the old ones with only minor changes in the coefficients, and the primary difference between the traditional and PIC approaches is in the broader confidence intervals given by the latter. We confirm the lower VE/VO2 ratio for birds compared to mammals and observe a common scaling of inspiratory flow and oxygen consumption for birds as has been reported for mammals. Use of allometrics and comparisons among avian groups are also discussed.

Animals↗
PubMedDate not supplied

Predation intensity does not cause microevolutionary change in maximum speed or aerobic capacity in trinidadian guppies (Poecilia reticulata Peters).

We measured maximal oxygen consumption (VO(2max)) and burst speed in populations of Trinidadian guppies (Poecilia reticulata) from contrasting high- and low-predation habitats but reared in "common garden" conditions. We tested two hypothesis: first, that predation, which causes rapid life-history evolution in guppies, also impacts locomotor physiology, and second, that trade-offs would occur between burst and aerobic performance. VO(2max) was higher than predicted from allometry, and resting VO(2) was lower than predicted. There were small interdrainage differences in male VO(2max), but predation did not affect VO(2max) in either sex. Maximum burst speed was correlated with size; absolute burst speed was higher in females, but size-adjusted speed was greater in males. For both sexes, burst speed conformed to allometric predictions. There were differences in burst speed between drainages in females, but predation regime did not affect burst speed in either sex. We did not find a significant correlation between burst speed and VO(2max), suggesting no trade-off between these traits. These results indicate that predation-mediated evolution of guppy life history does not produce concomitant evolution in aerobic capacity and maximum burst speed. However, other aspects of swimming performance (response latencies or acceleration) might show adaptive divergence in contrasting predation regimes.

Adaptation, Physiological↗
PubMed2004

Similarity of mammalian body size across the taxonomic hierarchy and across space and time.

Although it is commonly assumed that closely related animals are similar in body size, the degree of similarity has not been examined across the taxonomic hierarchy. Moreover, little is known about the variation or consistency of body size patterns across geographic space or evolutionary time. Here, we draw from a data set of terrestrial, nonvolant mammals to quantify and compare patterns across the body size spectrum, the taxonomic hierarchy, continental space, and evolutionary time. We employ a variety of statistical techniques including "sib-sib" regression, phylogenetic autocorrelation, and nested ANOVA. We find an extremely high resemblance (heritability) of size among congeneric species for mammals over approximately 18 g; the result is consistent across the size spectrum. However, there is no significant relationship among the body sizes of congeneric species for mammals under approximately 18 g. We suspect that life-history and ecological parameters are so tightly constrained by allometry at diminutive size that animals can only adapt to novel ecological conditions by modifying body size. The overall distributions of size for each continental fauna and for the most diverse orders are quantitatively similar for North America, South America, and Africa, despite virtually no overlap in species composition. Differences in ordinal composition appear to account for quantitative differences between continents. For most mammalian orders, body size is highly conserved, although there is extensive overlap at all levels of the taxonomic hierarchy. The body size distribution for terrestrial mammals apparently was established early in the Tertiary, and it has remained remarkably constant over the past 50 Ma and across the major continents. Lineages have diversified in size to exploit environmental opportunities but only within limits set by allometric, ecological, and evolutionary constraints.

Animals↗
PubMed2004

Affording larger brains: testing hypotheses of mammalian brain evolution on bats.

Several major hypotheses have been proposed to explain how larger brains in mammals, such as those of humans, are afforded in energetic terms. To date, these have been largely tested on primates, with some cross-mammal analysis. We use morphological, ecological, and metabolic data for 313 species of bats to examine the allometry of brain mass and to test key predictions from three of these hypotheses: the direct metabolic constraint, expensive tissue, and maternal energy hypotheses. We confirm that megachiropteran bats (entirely fruit-eating) have larger brains for their body mass than microchiropteran bats (fruit-eating and non-fruit-eating) and fruit-eating species (Megachiroptera and Microchiroptera) have larger brains than non-fruit-eating species (Microchiroptera). Although our analyses demonstrate little or no support for any of the three hypotheses, we show that 95.9% of the variance in brain mass can be explained by the independent effects of gestation length and body mass. This indicates that among bats, the duration of maternal investment plays an important role in the adult brain mass finally obtained. These analyses serve to emphasis the crucial importance of testing the general applicability of macroevolutionary hypotheses (often developed in isolation in one clade) in multiple clades with different evolutionary histories.

Adaptation, Physiological↗
PubMed2005

In vivo bone strain and ontogenetic growth patterns in relation to life-history strategies and performance in two vertebrate taxa: goats and emu.

This study examined ontogenetic patterns of limb loading, bone strains, and relative changes in bone geometry to explore the relationship between in vivo mechanics and size-related changes in the limb skeleton of two vertebrate taxa. Despite maintaining similar relative limb loads during ontogeny, bone strain magnitudes in the goat radius and emu tibiotarsus generally increased. However, while the strain increases in the emu tibiotarsus were mostly insignificant, strains within the radii of adult goats were two to four times greater than in young goats. The disparity between ontogenetic strain increases in these taxa resulted from differences in ontogenetic scaling patterns of the cross-sectional bone geometry. While the cross-sectional and second moments of area scaled with negative allometry in the goat radius, these measures were not significantly different from isometry in the emu tibiotarsus. Although the juveniles of both taxa exhibited lower strains and higher safety factors than the adults, the radii of the young goats were more robust relative to the adult goats than were the tibiotarsi of the young compared with adult emu. Differences in ontogenetic growth and strain patterns in the limb bones examined likely result from different threat avoidance strategies and selection pressures in the juveniles of these two taxa.

Animals↗
PubMed2006

The offspring-size/clutch-size trade-off in mammals.

The Smith-Fretwell model for optimal offspring size assumes the existence of an inverse proportional relationship (i.e., trade-off) between the number of offspring and the amount of resources invested in an individual offspring; virtually all of the many models derived from theirs make the same trade-off assumption. Over the last 30 years it has become apparent that the predicted proportionality is often not observed when evaluated across species. We develop a general allometric approach to correct for size-related differences in the resources available for reproduction. Using data on mammals, we demonstrate that the predicted inverse proportional relationship between number of offspring and offspring size is closely approached after correcting for allocation, though there is a slight curvature in the relationship. We discuss applications for this approach to other organisms, possible causes for the curvature, and the usefulness of allometries for estimating life-history variables that are difficult to measure.

Animals↗
PubMedDate not supplied

Low cost of locomotion in the banded Gecko: a test of the nocturnality hypothesis.

This study tested the hypothesis that there has been an evolutionary increase in locomotor performance capacity at low temperature in nocturnal lizards. Nocturnal lizards are often active at low and suboptimal body temperatures. An evolutionary decrease in the minimum cost of locomotion could increase endurance capacity at low temperature, partially offsetting the thermal handicap of nocturnality. In support of the nocturnality hypothesis, we discovered that minimum cost of locomotion of a nocturnal gecko, Coleonyx variegatus (4.2 g), was only 58% of the minimum cost of locomotion of Phrynosoma douglassii, a diurnal lizard (4.5 g). As a result, maximum aerobic speed was 2.3 times as great in the nocturnal lizard compared to the diurnal lizard. By using the method of phylogenetically independent contrasts at the species level, we showed that the relationship between mass and minimum cost of locomotion in diurnal lizards was similar to that of the ahistorical standard allometry and that low minimum cost of locomotion in geckos represents a significant evolutionary change from the ancestral diurnal pattern. The decrease in the minimum cost of locomotion concordant with the evolution of nocturnality suggests that geckos evolved a greater capacity for sustained locomotion at low temperature.

Animals↗