Biomechanics of Running Indicates Endothermy in Bipedal Dinosaurs

Background

One of the great unresolved controversies in paleobiology is whether extinct dinosaurs were endothermic, ectothermic, or some combination thereof, and when endothermy first evolved in the lineage leading to birds. Although it is well established that high, sustained growth rates and, presumably, high activity levels are ancestral for dinosaurs and pterosaurs (clade Ornithodira), other independent lines of evidence for high metabolic rates, locomotor costs, or endothermy are needed. For example, some studies have suggested that, because large dinosaurs may have been homeothermic due to their size alone and could have had heat loss problems, ectothermy would be a more plausible metabolic strategy for such animals.

Methodology/Principal Findings

Here we describe two new biomechanical approaches for reconstructing the metabolic rate of 14 extinct bipedal dinosauriforms during walking and running. These methods, well validated for extant animals, indicate that during walking and slow running the metabolic rate of at least the larger extinct dinosaurs exceeded the maximum aerobic capabilities of modern ectotherms, falling instead within the range of modern birds and mammals. Estimated metabolic rates for smaller dinosaurs are more ambiguous, but generally approach or exceed the ectotherm boundary.

Conclusions/Significance

Our results support the hypothesis that endothermy was widespread in at least larger non-avian dinosaurs. It was plausibly ancestral for all dinosauriforms (perhaps Ornithodira), but this is perhaps more strongly indicated by high growth rates than by locomotor costs. The polarity of the evolution of endothermy indicates that rapid growth, insulation, erect postures, and perhaps aerobic power predated advanced “avian” lung structure and high locomotor costs.     

Metabolic cost of acute phase response in the frugivorous bat, <Emphasis Type="Italic">Artibeus lituratus</Emphasis>

Bats play a key role as host for multiple microorganism and virus without showing clinical manifestations of disease. After recognition of a potential threat, innate immunity triggers acute phase response, a systemic reaction that contributes to restrain microbial and viral growth. APR is characterized by fever, leukocytosis, and production of acute phase proteins, but also by behavioral changes, including somnolence, lethargy, and anorexia. Deploying immune responses, such as acute phase response, represents an energetic cost for vertebrates. In bats, it has been suggested that higher metabolic rates reached during flight might subsidize any inherent cost of raising metabolism to activate an immune response. Therefore, a central question is whether immune response represents a significant cost to bats and, if so, how much is the metabolic cost of these responses. Here, we assess the resting metabolic rate of Artibeus lituratus in response to challenge with LPS. In addition, we assessed parameters of acute phase response including fever, body mass loss, and leukocytosis in this specie. We found that challenge with LPS leads to an increase of 40% in resting metabolic rate of A. lituratus, concomitant with body mass loss and an increase in body temperature of 1.5 °C.     

The cost of enzyme synthesis in the genetics of energy balance and physiological performance

The study of metabolism has traditionally focused upon factors that influence metabolic rate, at levels of both the metabolic pathway and the whole organism. This paper focuses on the cost, and thereby the efficiency, of metabolic processes. The genotype-dependent cost of enzyme turnover is proposed as a biochemical genetic mechanism for relating genetic variation at single genes to phenotypic variation in quantitative traits of energy metabolism. Decreased costs of maintenance metabolism can accompany artificial selection for increased production (e.g. growth, reproduction, etc.) and lower maintenance is correlated with multiple locus heterozygosity in outbred populations. In both cases, high production has been associated with lower rates of protein turnover. Several factors influence the ATP-equivalent cost of enzyme turnover. These factors are used to calculate the cost of turnover for a single enzyme. This cost can conservatively constitute up to several percent of the total daily mass-specific energy demands of maintenance metabolism. Genetic variants of an enzyme can differ in the cost of turnover. These differences can constitute the basis for metabolic changes associated with artificial selection for production and the metabolic differences that are associated with individual levels of heterozygosity. The metabolic and evolutionary significance of genotype-dependent turnover costs is a function of individual energy balance. The strength of selection against increases in cost will be an inverse function of individual energy balance and is therefore influenced by both environmental and genetic factors.     

Influence of the Crc global regulator on substrate uptake rates and the distribution of metabolic fluxes in Pseudomonas putida KT2440 growing in a complete medium

When the soil bacterium Pseudomonas putida grows in a complete medium, it prioritizes the assimilation of preferred carbon sources, optimizing its metabolism and growth. This regulatory process is orchestrated by the Crc and Hfq proteins. The present work examines the changes that occur in metabolic fluxes when the crc gene is inactivated and cells grow exponentially in LB complete medium. Analyses were performed at three different moments during exponential growth, examining the assimilation rates for the compounds present in LB, changes in the proteome, and the changes in metabolic fluxes predicted by the iJN1411 metabolic model for P. putida KT2440. During the early exponential phase, consumption rates for sugars, many organic acids and most amino acids were higher in a Crc-null strain than in the wild type, leading to an overflow of the metabolic pathways and the leakage of pyruvate and acetate. These accelerated consumption rates decreased during the mid-exponential phase, when cells mostly used sugars and alanine. At later times, pyruvate was recovered from the medium and utilized. The higher consumption rates of the Crc-null strain reduced the growth rate. The lack of the Crc/Hfq regulatory system thus led to unbalanced metabolism with poorly optimized metabolic fluxes.     

Fundamental Causes of the Global Patterns of Species Range and Richness1

Global patterns of species range and richness are a consequence of many interacting factors, including environmental conditions, competition, geographical area, and historical/evolutionary development. Two widely studied global patterns of distribution are the latitudinal and elevation gradients of species range and richness. The fundamental mechanisms by which environment and physiology of the plants themselves interact to generate global-scale correlations between increased species range or decreased species richness and latitude/elevation have not previously been established. This paper develops the hypothesis that the primary climatic variables determining global-scale gradients in ectotherm species range and richness are temperature (T) and temperature variability (T), and that the primary physiological variable defining adaptation of ectotherms to temperature is respiratory energy metabolism. This hypothesis is based on a postulate that adaptation of ectotherms to latitudinal/altitudinal gradients of T and T leads to corresponding gradients in properties of energy metabolism. The gradients of metabolic properties give rise to gradients of species range and richness that are observed on a global scale. We demonstrate that natural selection results in ectotherms with metabolic properties matched to their environment and that energy use efficiency and the temperature range allowing growth are inversely related. Thus, opposing selective pressures to increase metabolic energy-use-efficiency or to increase the probability of surviving climate extremes control adaptation of ectotherms to climate. The principles developed in this paper yield fundamental laws of ecology that allow calculation of the contributions of global temperature patterns to the formation of gradients of species range and diversity. Relative values of richness and range are calculated solely from data on abiotic variables. Predictions agree with known patterns of ectotherm distribution.     

Changes in metabolism in response to fasting and food restriction in the Steller sea lion (Eumetopias jubatus)

Many animals lower their resting metabolism (metabolic depression) when fasting or consuming inadequate food. We sought to document this response by subjecting five Steller sea lions to periods of: (1) complete fasting; or (2) restricting them to 50% of their normal herring diet. The sea lions lost an average of 1.5% of their initial body mass per day (2.30 kg/d) during the 9-14-day fast, and their resting metabolic rates decreased 31%, which is typical of a "fasting response". However, metabolic depression did not occur during the 28-day food restriction trials, despite the loss of 0.30% of body mass per day (0.42 kg/d). This difference in response suggests that undernutrition caused by reduced food intake may stimulate a "hunger response", which in turn might lead to increased foraging effort. The progressive changes in metabolism we observed during the fasts were related to, but were not directly caused by, changes in body mass from control levels. Combining these results with data collected from experiments when Steller sea lions were losing mass on low energy squid and pollock diets reveals a strong relationship between relative changes in body mass and relative changes in resting metabolism across experimental conditions. While metabolic depression caused by fasting or consuming large amounts of low energy food reduced the direct costs from resting metabolism, it was insufficient to completely overcome the incurred energy deficit.     

Staying alive

Quiescence is a state of reversible cell cycle arrest that can grant protection against many environmental insults. In some systems, cellular quiescence is associated with a low metabolic state characterized by a decrease in glucose uptake and glycolysis, reduced translation rates and activation of autophagy as a means to provide nutrients for survival. For cells in multiple different quiescence model systems, including Saccharomyces cerevisiae, mammalian lymphocytes and hematopoietic stem cells, the PI3Kinase/TOR signaling pathway helps to integrate information about nutrient availability with cell growth rates. Quiescence signals often inactivate the TOR kinase, resulting in reduced cell growth and biosynthesis. However, quiescence is not always associated with reduced metabolism; it is also possible to achieve a state of cellular quiescence in which glucose uptake, glycolysis and flux through central carbon metabolism are not reduced. In this review, we compare and contrast the metabolic changes that occur with quiescence in different model systems.     

Staying alive: Metabolic adaptations to quiescence

Quiescence is a state of reversible cell cycle arrest that can grant protection against many environmental insults. In some systems, cellular quiescence is associated with a low metabolic state characterized by a decrease in glucose uptake and glycolysis, reduced translation rates and activation of autophagy as a means to provide nutrients for survival. For cells in multiple different quiescence model systems, including Saccharomyces cerevisiae, mammalian lymphocytes and hematopoietic stem cells, the PI3Kinase/TOR signaling pathway helps to integrate information about nutrient availability with cell growth rates. Quiescence signals often inactivate the TOR kinase, resulting in reduced cell growth and biosynthesis. However, quiescence is not always associated with reduced metabolism; it is also possible to achieve a state of cellular quiescence in which glucose uptake, glycolysis and flux through central carbon metabolism are not reduced. In this review, we compare and contrast the metabolic changes that occur with quiescence in different model systems.     

A systems biology approach to investigate the antimicrobial activity of oleuropein

Oleuropein and its hydrolysis products are olive phenolic compounds that have antimicrobial effects on a variety of pathogens, with the potential to be utilized in food and pharmaceutical products. While the existing research is mainly focused on individual genes or enzymes that are regulated by oleuropein for antimicrobial activities, little work has been done to integrate intracellular genes, enzymes and metabolic reactions for a systematic investigation of antimicrobial mechanism of oleuropein. In this study, the first genome-scale modeling method was developed to predict the system-level changes of intracellular metabolism triggered by oleuropein in Staphylococcus aureus, a common food-borne pathogen. To simulate the antimicrobial effect, an existing S. aureus genome-scale metabolic model was extended by adding the missing nitric oxide reactions, and exchange rates of potassium, phosphate and glutamate were adjusted in the model as suggested by previous research to mimic the stress imposed by oleuropein on S. aureus. The developed modeling approach was able to match S. aureus growth rates with experimental data for five oleuropein concentrations. The reactions with large flux change were identified and the enzymes of fifteen of these reactions were validated by existing research for their important roles in oleuropein metabolism. When compared with experimental data, the up/down gene regulations of 80% of these enzymes were correctly predicted by our modeling approach. This study indicates that the genome-scale modeling approach provides a promising avenue for revealing the intracellular metabolism of oleuropein antimicrobial properties.     

Theoretical and methodological bases of experimental simulation of the prepathological state under membrane-damaging effects of environmental factors

The paper theoretically substantiates the importance for detecting the prepathological state of experimental simulation of those situations in the organism which adequately reflect changes in human metabolism exposed to multiple environmental factors. A putative experimental model has been proposed in the shape of sexually immature and mature generations of animals of differing age with a "metabolic burden" whose characteristics, as regards impairments in biochemical, immunological and other functional reactions in biological fluids, are to some extent similar to those occurring in certain groups of humans. It has been suggested that the further investigation of the mechanisms and biological significance of systemic changes of the body's internal milieu may hold promise for studies of environmental hygiene in evaluating populational health and detecting the early signs of metabolic alterations with the aim of their timely prevention.     

The energetics of starvation and growth after refeeding in juveniles of three cyprinid species

Synopsis Experiments were conducted to monitor changes in body mass and metabolic energy expenditure before, during, and after periods of starvation in juveniles of three species of cyprinids: Leuciscus cephalus, Chalcalburnus chalcoides mento, and Scardinius erythrophthalmus. During the starvation period all fish lost weight at about the same rate and the total amount of oxygen consumed during an experimental period of 20 h was about 40% lower in the starved than in the fed groups. Upon refeeding, both mass specific maintenance; and routine rates of metabolism as well as relative growth rates increased rapidly, the peaks of these increases being directly proportional to the length of the starvation period. Maximum compensatory growth was observed after four weeks of starvation in C. chalcoides and S. erythrophthalmus, with relative growth rates reaching 30% d^-1 during the first measuring interval after refeeding. The pattern of time-dependent compensatory growth displayed by these fish is similar to the responses of a colonial hydroid in which the rate of catch-up growth increased with the amount of stress to which the animals had been exposed. The exact cost of compensatory growth cannot be calculated because oxygen consumption and growth were not measured simultaneously. However, on the basis of data and calculations reported by Wieser & Medgyesy (1990) it appears that compensatory growth, if fuelled by the metabolic power indicated by our measurements of oxygen consumption, would have to be about twice as efficient as normal growth in the related species Rutilus rutilus.     

Is metabolic rate a universal ‘pacemaker’ for biological processes?

A common, long‐held belief is that metabolic rate drives the rates of various biological, ecological and evolutionary processes. Although this metabolic pacemaker view (as assumed by the recent, influential ‘metabolic theory of ecology’) may be true in at least some situations (e.g. those involving moderate temperature effects or physiological processes closely linked to metabolism, such as heartbeat and breathing rate), it suffers from several major limitations, including: (i) it is supported chiefly by indirect, correlational evidence (e.g. similarities between the body‐size and temperature scaling of metabolic rate and that of other biological processes, which are not always observed) – direct, mechanistic or experimental support is scarce and much needed; (ii) it is contradicted by abundant evidence showing that various intrinsic and extrinsic factors (e.g. hormonal action and temperature changes) can dissociate the rates of metabolism, growth, development and other biological processes; (iii) there are many examples where metabolic rate appears to respond to, rather than drive the rates of various other biological processes (e.g. ontogenetic growth, food intake and locomotor activity); (iv) there are additional examples where metabolic rate appears to be unrelated to the rate of a biological process (e.g. ageing, circadian rhythms, and molecular evolution); and (v) the theoretical foundation for the metabolic pacemaker view focuses only on the energetic control of biological processes, while ignoring the importance of informational control, as mediated by various genetic, cellular, and neuroendocrine regulatory systems. I argue that a comprehensive understanding of the pace of life must include how biological activities depend on both energy and information and their environmentally sensitive interaction. This conclusion is supported by extensive evidence showing that hormones and other regulatory factors and signalling systems coordinate the processes of growth, metabolism and food intake in adaptive ways that are responsive to an organism's internal and external conditions. Metabolic rate does not merely dictate growth rate, but is coadjusted with it. Energy and information use are intimately intertwined in living systems: biological signalling pathways both control and respond to the energetic state of an organism. This review also reveals that we have much to learn about the temporal structure of the pace of life. Are its component processes highly integrated and synchronized, or are they loosely connected and often discordant? And what causes the level of coordination that we see? These questions are of great theoretical and practical importance.     

Ocean acidification may increase calcification rates, but at a cost

Ocean acidification is the lowering of pH in the oceans as a result of increasing uptake of atmospheric carbon dioxide. Carbon dioxide is entering the oceans at a greater rate than ever before, reducing the ocean's natural buffering capacity and lowering pH. Previous work on the biological consequences of ocean acidification has suggested that calcification and metabolic processes are compromised in acidified seawater. By contrast, here we show, using the ophiuroid brittlestar Amphiura filiformis as a model calcifying organism, that some organisms can increase the rates of many of their biological processes (in this case, metabolism and the ability to calcify to compensate for increased seawater acidity). However, this upregulation of metabolism and calcification, potentially ameliorating some of the effects of increased acidity comes at a substantial cost (muscle wastage) and is therefore unlikely to be sustainable in the long term.     

Effects of cold stress during diapause on the survival and development ofDelia radicum (Diptera: Anthomyiidae) in England

Summary In this review I offer a solution to the problem why endotherm populations appear to be so inefficient in converting food energy into body substance despite the fact that individual endotherms are just as efficient in this respect as individual ectotherms. Calculated for individuals of half the adult mass both ectotherms and endotherms convert about the same proportion of food energy into somatic growth although for a given body mass the latter expend about 10 times more aerobic power than the former. On the other hand, early in life, during the period of maximum growth, ectotherms channel a 2–3 times greater percentage of metabolic energy into growth than endotherms. Even greater becomes the difference between these two groups if we consider the relative cost of reproduction. It can be shown that, weight by weight, nematodes, fish, birds and mammals require almost the same amount of energy for the production of offspring-, roughly 250 kJ per day and kg of eggs, hatchlings or litter. However, whereas the cost of producing offspring represents only 2%–6% of the total metabolizable energy of an endotherm, a fish has to spend 35%, a nematode nearly everything it has for this purpose. This may explain the finding by Humphreys (1979) and others that in nature the production, efficiencies of endotherm populations appear to be at least one order of magnitude lower than those of ectotherm populations. However, rather than calling endotherms less efficient energy converters, I suggest that by increasing total metabolic power more than ten-fold but keeping the energy cost of reproduction constant, this group of animals achieved emancipation from the burden of reproduction. Conversely, ectotherms have to channel a much greater proportion of metabolic power into reproduction because only in this way are they able to fit their low-rate life cycle schedules into the ecological schedules of the environment.     

Bioenergetic model of planktivorous fish feeding, growth and metabolism: theoretical optimum swimming speed of fish larvae

The feeding activity of an individual fish larva is described by an equation which includes parameters for the area successfully searched, probability of food capture multiplied by the cross-sectional perceptive visual field, larval swimming speed and the time required to consume a unit of food energy. The proportion of ingested food energy used for metabolism increases exponentially with increasing swimming speed. The model predicts that food consumption rate increases asymptotically whereas metabolic rate increases exponentially. This results in a predicted growth rate curve that reaches a maximum at a certain swimming speed and decreases at both higher and lower speeds. The model can be used to predict the influence of type of prey, prey density, water temperature etc. on larval growth. An expression describing how many hours per day fish larvae must forage in order to grow at a certain daily body weight gain allows the limits of environmental conditions for positive, zero and negative growth rate to be set. Results of simulations demonstrated that the optimum swimming speed for maximum growth of coregonid larvae increased with an increase in food density, decrease in water temperature or decrease of prey vulnerability. At optimum ‘theoretical’ swimming speed an increase in water temperature from 5 to 17° C required the food density to be increased from 20 to 80 copepods l^?1 in order to maintain a daily growth increment of 2%. The minimum Artemia density required for maintenance metabolism increased from 10 to 30 items 1¹ over the same temperature increase from 5 to 17° C, and food densities required for 8% growth rates were 26 and 56 Artemia nauplii l^?1 at 5 and 17° C, respectively. Contrary to previous findings, results of the present study suggest that metabolic rates of actively feeding fish larvae may be from 5 to 50 times the standard metabolic rate: earlier studies suggested that a factor of 2–3 may be generally applicable.     

Pseudomonas putida KT2440 metabolism undergoes sequential modifications during exponential growth in a complete medium as compounds are gradually consumed

Pseudomonas putida is a soil bacterium with a versatile and robust metabolism. When confronted with mixtures of carbon sources, it prioritizes the utilization of the preferred compounds, optimizing metabolism and growth. This response is particularly strong when growing in a complex medium such as LB. This work examines the changes occurring in P. putida KT2440 metabolic fluxes, while it grows exponentially in LB medium and sequentially consumes the compounds available. Integrating the uptake rates for each compound at three different moments during the exponential growth with the changes observed in the proteome, and with the metabolic fluxes predicted by the iJN1411 metabolic model for this strain, allowed the metabolic rearrangements that occurred to be determined. The results indicate that the bacterium changes significantly the configuration of its metabolism during the early, mid and late exponential phases of growth. Sugars served as an energy source during the early phase and later as energy and carbon source. The configuration of the tricarboxylic acids cycle varied during growth, providing no energy in the early phase, and turning to a reductive mode in the mid phase and to an oxidative mode later on. This work highlights the dynamism and flexibility of P. putida metabolism.     

Metabolic cost of walking: equation and model

Twenty years of published experience with the Workman-Armstrong equation for predicting walking VO2 is reviewed. The equation is reexpressed in currently accepted terminology, and it is shown that the equation serves well as a basic model of normal walking. Employing this model to analyze VO2/step leads to the elaboration of a three-compartment model of the metabolic cost of walking. This three-compartment model provides a rational estimate of the fraction of walking's metabolic cost that powers the actual walking movement. Doubt is expressed that "comfortable speed of walking" is definable in energy terms. It is suggested that the requirements of maintaining balance while walking may determine both the comfortable speed of walking and the curvilinearity of the relationship between ground-speed and freely chosen step frequency of walking.     

Metabolic network modularity in archaea depends on growth conditions

Network modularity is an important structural feature in metabolic networks. A previous study suggested that the variability in natural habitat promotes metabolic network modularity in bacteria. However, since many factors influence the structure of the metabolic network, this phenomenon might be limited and there may be other explanations for the change in metabolic network modularity. Therefore, we focus on archaea because they belong to another domain of prokaryotes and show variability in growth conditions (e.g., trophic requirement and optimal growth temperature), but not in habitats because of their specialized growth conditions (e.g., high growth temperature). The relationship between biological features and metabolic network modularity is examined in detail. We first show the absence of a relationship between network modularity and habitat variability in archaea, as archaeal habitats are more limited than bacterial habitats. Although this finding implies the need for further studies regarding the differences in network modularity, it does not contradict previous work. Further investigations reveal alternative explanations. Specifically, growth conditions, trophic requirement, and optimal growth temperature, in particular, affect metabolic network modularity. We have discussed the mechanisms for the growth condition-dependant changes in network modularity. Our findings suggest different explanations for the changes in network modularity and provide new insights into adaptation and evolution in metabolic networks, despite several limitations of data analysis.