Quantitative steps in the evolution of metabolic organisation as specified by the Dynamic Energy Budget theory

The Dynamic Energy Budget (DEB) theory quantifies the metabolic organisation of organisms on the basis of mechanistically inspired assumptions. We here sketch a scenario for how its various modules, such as maintenance, storage dynamics, development, differentiation and life stages could have evolved since the beginning of life. We argue that the combination of homeostasis and maintenance induced the development of reserves and that subsequent increases in the maintenance costs came with increases of the reserve capacity. Life evolved from a multiple reserves - single structure system (prokaryotes, many protoctists) to systems with multiple reserves and two structures (plants) or single reserve and single structure (animals). This had profound consequences for the possible effects of temperature on rates. We present an alternative explanation for what became known as the down-regulation of maintenance at high growth rates in microorganisms; the density of the limiting reserve increases with the growth rate, and reserves do not require maintenance while structure-specific maintenance costs are independent of the growth rate. This is also the mechanism behind the variation of the respiration rate with body size among species. The DEB theory specifies reserve dynamics on the basis of the requirements of weak homeostasis and partitionability. We here present a new and simple mechanism for this dynamics which accounts for the rejection of mobilised reserve by busy maintenance/growth machinery. This module, like quite a few other modules of DEB theory, uses the theory of Synthesising Units; we review recent progress in this field. The plasticity of membranes that evolved in early eukaryotes is a major step forward in metabolic evolution; we discuss quantitative aspects of the efficiency of phagocytosis relative to the excretion of digestive enzymes to illustrate its importance. Some processes of adaptation and gene expression can be understood in terms of allocation linked to the relative workload of metabolic modules in (unicellular) prokaryotes and organs in (multicellular) eukaryotes. We argue that the evolution of demand systems can only be understood in the light of that of supply systems. We illustrate some important points with data from the literature.     

A Dynamic Energy Budget model based on partitioning of net production

We formulate a Dynamic Energy Budget (DEB) model for the growth and reproduction of individual organisms based on partitioning of net production (i.e. energy acquisition rate minus maintenance rate) between growth and energy reserves. Reproduction uses energy from reserves. The model describes both feeding and non-feeding stages, and hence is applicable to embryos (which neither feed nor reproduce), juveniles (which feed but do not reproduce), and adults (which commonly both feed and reproduce). Embryonic growth can have two forms depending on the assumptions for acquisition of energy from yolk. By default, when the energy acquisition rate exceeds the maintenance rate, a fixed proportion of the resulting net production is spent on growth (increase in structural biomass), and the remaining portion is channelled to the reserves. Feeding organisms, however, modulate their allocation of net production energy in response to their total energy content (energy in the reserves plus energy bounded to structural biomass). In variable food environment an organism alternates between periods of growth, no-growth, and balanced-growth. In the latter case the organism adopts an allocation strategy that keeps its total energy constant. Under constant environmental conditions, the growth of a juvenile is always of von Bertalanffy type. Depending on the values of model parameters there are two long-time possibilities for adults: (a) von Bertalanffy growth accompanied by reproduction at a rate that approaches zero as the organism approaches asymptotic size, or (b) abrupt cessation of growth at some finite time, following which, the rate of reproduction is constant. We illustrate the model's applicability in life history theory by studying the optimum values of the energy allocation parameters for constant environment and for each of the dynamic regimes described above. Received: 11 May 1998 / Revised version: 18 February 2000 / Published online: 4 October 2000     

Survival and production in variable resource environments

A dynamic energy budget (DEB) model describes the rates at which organisms assimilate and utilize energy from food for maintenance, growth, reproduction and development. We study the dynamic behavior of one particular DEB model, Kooijman’s κ rule model, whose key assumption is that somatic and reproductive tissues are competing for energy. We assume an environment in which the food density fluctuates either periodically or stochastically (pink noise). Both types of fluctuations stimulate growth; the magnitude of the (average) increase in size depends on both the strength and duration of the fluctuations. In a stochastic environment, the risk of mortality due to starvation increases with increasing fluctuation intensity. The mean lifespan is also a function of the model parameter κ characterizing the partitioning of energy between somatic and reproductive tissues. Organisms committing a large fraction of resources to reproduction endure periods of food shortage relatively well. The effects of food fluctuations on reproduction are complex. With stochastic food, reproduction in survivors increases with increasing fluctuation intensities, but lifetime reproduction decreases. Periodic fluctuations may enhance reproduction, depending on the value of κ. Thus, a variable food supply stimulates growth, increases mortality and may enhance reproduction, depending on life history.     

Neural mechanisms of target ranging in FM bats: physiological evidence from bats and frogs

Echolocating bats assess target range by the delay in echo relative to the emitted sonar pulse. Earlier studies in FM bats showed that a population of neurons in auditory centers above the inferior colliculus (IC) is tuned to echo delay, with different neurons tuned to different echo delays. A building block for delay-tuned responses is paradoxical latency shift (PLS), featuring longer response latencies to more intense sounds. PLS is first created in the IC, where neurons exhibit unit-specific quantum increase in response latency with increasing sound level. Other IC neurons display oscillatory discharges whose period is unit-specific and level tolerant, indicating that this is attributable to cell’s intrinsic properties. High-threshold inhibition of oscillatory discharge produces PLS, indicating that oscillatory discharge is a building block for PLS. To investigate the cellular basis of oscillatory discharges, we performed whole-cell patch-clamp recordings from IC neurons in leopard frogs (which also exhibit oscillatory discharges and PLS). These recordings show that IC neurons are heterogeneous displaying diverse biophysical phenotypes; each phenotype (and cell) has its own membrane time constant, input resistance, and strengths of I _h, I _kir, I _kv—these intrinsic properties give rise to cell-specific resonance which can be observed through current and afferent stimulations.     

Sucrose metabolism and cell elongation in developing sunflower hypocotyls

The relationships between cell elongation and changes in specificactivities of enzymes of sucrose metabolism were investigatedin the growing region of hypocotyls of sunflower seedlings {Helianthusannuus L.) that were grown either in darkness or irradiatedwith continuous white light (WL). After transfer of dark–grownseedlings into WL an inhibition of cell elongation was observed.In etiolated stems, changes in enzymes of sucrose breakdown(acid invertase, sucrose synthase) were closely correlated withthe rate of cell elongation. Irradiation with WL induced a largedrop in acid invertase and a significant decrease in sucrosesynthase. The changes in concentration of sucrose were inverselycorrelated with the activities of the sucrose breakdown enzymes.A short–term experiment revealed that the effect of WLon growth was more rapid than the inhibitory effect on invertaseactivity. In dark–grown stems the activities of enzymesof sucrose biosynthesis (sucrose–phosphate synthase, ribulose1,5 bisphosphate carboxylase/oxygenase) were very low. AfterWL irradiation significant enhancements were measured. However,activities of enzymes of sucrose breakdown were still much largerthan those of sucrose biosynthesis, indicating that the green(de–etiolated) stem remains a sink for sucrose. We suggestthat the relative maintenance of cell osmotic pressure and turgorduring rapid cell elongation in darkness is due to enhancedhydrolysis of imported sucrose, which is cleaved by two enzymes(invertase, sucrose synthase). This process is regulated bylight and hence is under environmental control. Key words: Cell elongation, organ growth, Helianthus annuu, sucrose metabolism, source-sink relationship     

Cell energy metabolism: An update

In living cells, growth is the result of coupling between substrate catabolism and multiple metabolic processes that take place during net biomass formation and maintenance processes. During growth, both ATP/ADP and NADH/NAD⁺ molecules play a key role. Cell energy metabolism hence refers to metabolic pathways involved in ATP synthesis linked to NADH turnover. Two main pathways are thus involved in cell energy metabolism: glycolysis/fermentation and oxidative phosphorylation. Glycolysis and mitochondrial oxidative phosphorylation are intertwined through thermodynamic and kinetic constraints that are reviewed herein. Further, our current knowledge of short-term and long term regulation of cell energy metabolism will be reviewed using examples such as the Crabtree and the Warburg effect.     

Respiratory energy costs for the maintenance of biomass, for growth and for ion uptake in roots of Carex diandra and Carex acudformis

van der Werf, A., Kooijman, A., Welschen, R. and Lambers, H. 1988. Respiratory energy costs for the maintenance of biomass, for growth and for ion uptake in roots of Carex diandra and Carex acutiformis. - Physiol. Plant. 72: 483–491. The respiratory characteristics of the roots of Carex diandra Schrank and Carex acutiformis Ehrh. were investigated. The aims were, firstly to determine the respiratory energy costs for the maintenance of root biomass, for root growth and for ion uptake, and secondly to explain the higher rate of root respiration and ATP production in C. diandra. The three respiratory energy components were derived from a multiple regression analysis, using the relative growth rate and the net rate of nitrate uptake as independent variables and the rate of ATP production as a dependent variable. Although the rate of root respiration and ATP production was significantly higher in C. diandra than in C. acutiformis, the two species showed no significant difference in their rate of ATP production for the maintenance of biomass, in the respiratory energy coefficient for growth (the amount of ATP production per unit of biomass produced) and the respiratory energy coefficient for ion uptake (amount of ATP production per unit of ions absorbed). It is concluded that the higher rate of root respiration of C. diandra is caused by a higher rate of nitrate uptake. At relatively high rates of growth and nitrate uptake, the contribution of the rate of ATP production for ion uptake to the total rate of ATP production amounted to 38 and 25% for C. diandra and C. acutiformis, respectively. At this growth rate, the respiratory energy production for growth contributed 37 and 50%, respectively, to the total rate of ATP production. The relative contribution of the rate of ATP production for the maintenance of biomass increased from 25 to 70% with increasing plant age for both species. The results suggest that ion uptake is one of the major sinks for respiratory energy in roots. These experimentally derived values for the rate of ATP production for the maintenance of biomass, the respiratory energy coefficient for growth and the respiratory energy coefficient for ion uptake are discussed in relation to other experimentally and theoretically derived values.     

Independence of the unimodal tuning of firing rate from theta phase precession in hippocampal place cells

There are two prominent features for place cells in rat hippocampus. The firing rate remarkably increases when rat enters the cell’s place field and reaches a maximum around the center of place field, and it decreases when the animal approaches the end of the place field. Simultaneously the spikes gradually and monotonically advance to earlier phase relative to hippocampal theta rhythm as the rat traverses along the cell’s place field, known as temporal coding. In this paper, we investigate whether two main characteristics of place cell firing are independent or not by mainly focusing on the generation mechanism of the unimodal tuning of firing rate by using a reduced CA1 two-compartment neuron model. Based on recent evidences, we hypothesize that the coupling of dendritic with the somatic compartment is not constant but dynamically regulated as the animal moves further along the place field, in contrast to previous two-compartment modeling. Simulations show that the regulable coupling is critically responsible for the generation of unimodal firing rate profile in place cells, independent of phase precession. Predictions of our model accord well with recent observations like occurrence of phase precession with very low as well as high firing rate (Huxter et al. Nature 425:828–832, 2003) and persistency of phase precession after transient silence of hippocampus activity (Zugaro et al. Nat Neurosci 8:67–71, 2005.     

A dynamic energy budget model: parameterisation and application to the Pacific oyster Crassostrea gigas in New Zealand waters

A dynamic energy budget (DEB) model was developed and applied to the Pacific oyster Crassostrea gigas in central New Zealand. The model was based on DEB theory and developed prior to empirical information according to a common mechanistic rule in organisms' physiology. Subsequently, both laboratory and field experiments were specifically designed to collect datasets for parameter estimation and testing of the model. This approach to the modelling aimed to reduce uncertainties in parameter estimates and hence improve the applicability of the model. A lab-based starvation experiment was done over 170 days. Changes in body flesh weight were monitored and the respiration rate was measured. Dry flesh weight and the oxygen consumption rate decreased by 63.4% and 44.0% respectively over the experiment. Ash free dry flesh weight was proportional to the dry flesh weight, with coefficients of 83.5% and 58.7% respectively at the beginning and late stages of the experiment. Field-based growth experiments were done on a marine farm at two depths over 150 days to obtain biological and environmental information. The growth rate of oysters at 8 m depth was significantly greater than at 32 m depth. Chlorophyll-a concentration was highly variable, both spatially and temporally. Variation between depths provided ideal information for validation of the DEB model. Estimates of model parameters were augmented from studies in a local population. In comparison with previous studies on the same species from other ecosystems in the world, intraspecies variation was apparent in some parameters including maximum surface area-specific assimilation rate, which governs the ability of an individual for energy acquisition, and the fraction of energy utilisation rate used for maintenance plus growth, which determines energy fluxes to different components. The maximum storage density and volume-specific cost for growth also showed considerable intraspecies variability. Application of the model developed here showed that it is capable of simulating energetics and growth of the oyster in the growing area of central New Zealand.     

Improved production of 2,3-butanediol and isobutanol by engineering electron transport chain in Escherichia coli

The electron transport chain (ETC) is one of the major energy generation pathways in microorganisms under aerobic condition. Higher yield of ATP can be achieved through oxidative phosphorylation with consumption of NADH than with substrate level phosphorylation. However, most value-added metabolites are in an electrochemically reduced state, which requires reducing equivalent NADH as a cofactor. Therefore, optimal production of value-added metabolites should be balanced with ETC in terms of energy production. In this study, we attempted to reduce the activity of ETC to secure availability of NADH. The ETC mutants exhibited poor growth rate and production of fermentative metabolites compared to parental strain. Introduction of heterologous pathways for synthesis of 2,3-butanediol and isobutanol to ETC mutants resulted in increased titres and yields of the metabolites. ETC mutants yielded higher NADH/NAD⁺ ratio but similar ATP content than that by the parental strain. Furthermore, ETC mutants operated fermentative metabolism pathways independent of oxygen supply in large-scale fermenter, resulting in increased yield and titre of 2,3-butanediol. Thus, engineering of ETC is a useful metabolic engineering approach for production of reduced metabolites.     

Mechanism of allosteric effects of ATP on the kinetics of P-type ATPases

The roles of allosteric effects of ATP and protein oligomerisation in the mechanisms of P-type ATPases belong to the most controversial and least well understood topics in the field. Recent crystal structural and kinetic data, however, now allow certain hypotheses to be definitely excluded and consistent hypotheses to be developed. The aim of this review is to critically discuss recent results and, in the light of them, to present a set of conclusions which could form the basis of future research. The major conclusions are: (1) at saturating ATP concentrations P-type ATPases function as monomeric enzymes, (2) the catalytic units of P-type ATPases only possess a single ATP binding site, (3) at non-saturating ATP concentrations P-type ATPases exist as diprotomeric (or higher oligomeric) complexes, (4) protein–protein interactions within a diprotomeric complex enhances the enzymes’ ATP binding affinity, (5) ATP binding to both protomers within a diprotomeric complex causes it to dissociate into two separate monomers. The physiological role of protein–protein interactions within a diprotomer may be to enhance ATP binding affinity so as to scavenge ATP and maximize the ion pumping rate under hypoxic or anoxic conditions. For the first time a structural basis for the well-known ATP allosteric acceleration of the E2 → E1 transition is presented. This is considered to be due to a minimization of steric hindrance between neighbouring protomers because of the ability of ATP to induce a compact conformation of the enzymes’ cytoplasmic domains.     

Transient responses of hybridoma cells to nutrient additions in continuous culture: I. Glucose pulse and step changes

Glucose and glutamine are the main nutrients used by mammalian cells in culture. Each provides unique biosynthetic precursors but are complementary for production of other metabolites and energy. The transient and steady-state responses of hybridoma growth and metabolism to glucose pulse and step changes have been examined. Metabolic quotients are reported for oxygen, glucose, lactate, ammonia, glutamine, alanine, and other amino acids. The glucose consumption rate increased by 100-200% immediately after glucose was added to the reactor, and the increased glycolytic ATP production appears to be responsible for the concurrent rapid decrease in the oxygen consumption rate. The effects on glutamine consumption were delayed, probably due to buffering by the TCA cycle and interrelated pathways. A period of increased biosynthetic activity, as evidenced by an increase in the estimated specific ATP production rate and lower by-product yields from glutamine, preceded the increase in cell concentration after the glucose step change. The biosynthetic yield of cells from ATP was calculated, and it was estimated that maintenance accounted for about 60% of the energy used by the cells at a specific growth rate of 0.66 day(-1). The estimated 22% ATP production due to glycoysis was twice as great as that before the step change.     

Bioenergetics and end-product regulation of Clostridium thermosaccharolyticum in response to nutrient limitation

Fermentation of xylose by Clostridium thermosaccharolyticum was studied in batch and continuous culture in which the limiting nutrient was either xylose, phosphate, or ammonia. Transient results obtained in continuous cultures with batch grown inoculum and progressively higher feed substrate concentrations exhibited ethanol selectivities (moles ethanol/moles other products) in excess of 11. The hypothesis that this high ethanol selectivity was a general response to mineral nutrient limitation was tested but could not be supported. Growth and substrate consumption were related by the equation q(s)(1 - Y(x) (c))G(ATP) = (mu/Y(ATP) (max)) + m, with q(s) the specific rate of xylose consumption (moles xylose/hour . g cells), Y(x) (c) the carbon based cell yield (g cell carbon/g substrate carbon), G(ATP) the ATP gain (moles ATP produces/mol substrate catabolized), mu the specific growth rate (1/h), Y(ATP) (max) the ATP-based cell yield (g cells/mol ATP), and m the maintenance coefficient (moles ATP/hour . g cells). Y(ATP) (max) was found to be 11.6 g cells/mol ATP, and m 9.3 mol ATP/hour . g cells for growth on defined medium. Different responses to nutrient limitation were observed depending on the mode of cultivation. Batch and immobilized cell continuous cultures decreased G(ATP) by initiating production of the secondary metabolites, propanediol, and in some cases, D-lactate; in addition, batch cultures increased the fractional allocation of ATP to maintenance and/or wastage. Nitrogen-limited continuous free-cell cultures maintained a constant cell yield, whereas phosphate-limited continuous free-cell cultures did not. In the case of phosphate limitation, the decreased ATP demand associated with the lowered cell yield was accompanied by an increased rate of ATP consumption for maintenance and/or wastage. Neither nitrogen or phosphorus-limited continuous free-cell cultures exhibited an altered G(ATP) in response to mineral nutrient limitation, and neither produced secondary metabolites. (c) 1993 John Wiley & Sons, Inc.     

Nucleoside diphosphate kinase A as a controller of AMP-kinase in airway epithelia

This review integrates recent understanding of a novel role for NDPK-A in two related directions: Firstly, its role in an airway epithelial cell when bound to the luminal (apical) membrane and secondly in the cytosol of many different cells (epithelial and non-epithelial) where an isoform-specific interaction occurs with a regulatory partner, AMPKα1. Thus NDPK-A is present in both a membrane and cytosolic environment but in the apical membrane, its roles are not understood in detail; preliminary data suggest that it co-localises with the cystic fibrosis protein (CFTR). In cytosol, we find that NDPK-A is coupled to the catalytic alpha1 isoform of the AMP-activated protein kinase (AMPKα subunit), which is part of a heterotrimeric protein complex that responds to cellular energy status by switching off ATP-consuming pathways and switching on ATP-generating pathways when ATP is limiting. We find that ATP is located within this complex and ‘fed’ from NDPK to AMPK without ever ‘seeing’ bulk solution. Importantly, the reverse can also happen such that AMPK activity can be made to decline when NDPK-A ‘steals’ ATP from AMPK. Thus we propose a novel paradigm in NDPK-A function by suggesting that AMP-kinase can be regulated by NDPK-A, independently of AMP.     

Energetics of bacterial growth: balance of anabolic and catabolic reactions.

Biomass formation represents one of the most basic aspects of bacterial metabolism. While there is an abundance of information concerning individual reactions that result in cell duplication, there has been surprisingly little information on the bioenergetics of growth. For many years, it was assumed that biomass production (anabolism) was proportional to the amount of ATP which could be derived from energy-yielding pathways (catabolism), but later work showed that the ATP yield (YATP) was not necessarily a constant. Continuous-culture experiments indicated that bacteria utilized ATP for metabolic reactions that were not directly related to growth (maintenance functions). Mathematical derivations showed that maintenance energy appeared to be a growth rate-independent function of the cell mass and time. Later work, however, showed that maintenance energy alone could not account for all the variations in yield. Because only some of the discrepancy could be explained by the secretion of metabolites (overflow metabolism) or the diversion of catabolism to metabolic pathways which produced less ATP, it appeared that energy-excess cultures had mechanisms of spilling energy. Bacteria have the potential to spill excess ATP in futile enzyme cycles, but there has been little proof that such cycles are significant. Recent work indicated that bacteria can also use futile cycles of potassium, ammonia, and protons through the cell membrane to dissipate ATP either directly or indirectly. The utility of energy spilling in bacteria has been a curiosity. The deprivation of energy from potential competitors is at best a teleological explanation that cannot be easily supported by standard theories of natural selection. The priming of intracellular intermediates for future growth or protection of cells from potentially toxic end products (e.g., methylglyoxal) seems a more plausible explanation.     

ATP调控策略及其在微生物代谢产物合成中的应用

辅因子工程是代谢工程的一个新兴分支领域,主要通过直接调控细胞内关键酶的辅因子,如ATP/ADP、NADH/NAD+、NADPH/NADP+等的浓度和形式来实现代谢流的最大化,快速地将物质流导向目标代谢物。ATP作为一种重要辅因子参与微生物细胞内大量的酶催化反应,将物质代谢途径串联或并联成复杂的网络体系,最终使得物质代谢流的分配受到牵制。因此ATP调控策略有望成为微生物菌株改造的有利工具,用于提高目标代谢物的浓度和生产能力,强化微生物对于环境的耐受以及促进底物利用等。文中将重点论述目前常用的有效ATP调控策略以及ATP调控对于细胞代谢的影响,以期为微生物细胞工厂的高效构建提供参考。     

Interactions between glucosinolate- and myrosinase-containing plants and the sawfly Athalia rosae

Several insects have specialised on using Brassicaceae as host plants. Therefore, they evolved metabolic pathways to cope with the defensive glucosinolate–myrosinase system of their diet. Larvae of the turnip sawfly, Athalia rosae L. (Hymenoptera: Tenthredinidae), incorporate various glucosinolates from their hosts into their haemolymph. The ability to sequester these metabolites makes A. rosae a useful model system to study mechanisms of glucosinolate metabolism in this species compared to other specialists, and to study effects of sawfly feeding on levels of glucosinolates and their hydrolysing enzymes in plants. The levels of plant metabolites might in turn directly affect the performance of the insect. On the one hand, costs for glucosinolate uptake and avoidance of myrosinase activity were postulated. On the other hand, sequestration of glucosinolates can be part of the insect’s defence against several predators. Here, the findings on glucosinolate metabolic pathways are compared between different herbivores and the sawfly. The impact of different glucosinolate levels and myrosinase activities on the performance of A. rosae is discussed. Furthermore, effects of feeding by A. rosae larvae on the chemical composition and enzyme activities of various Brassicaceae species are summarised. Induction patterns vary not only between different plant species and cultivars but also due to the inducing agent. Finally, the plant–herbivore interactions are discussed with regard to the sawflies’ defence abilities against different carnivore guilds.     

A multiplex PCR technique to characterize human bone marrow derived mesenchymal stem cells

Human mesenchymal stem cells (MSCs), with capacity to differentiate into adipocytes, osteoblasts and chondrocytes, offer potential for the development of novel treatments. A critical question in MSCs biology is whether this cell population possesses a relatively uniform differentiation capability or is comprised of distinct subsets of progenitors committed to differentiate in particular pathways. To quantify the changes during growth of MSCs, we analyzed the mesenchymal phenotype and differentiation ability using a multi-marker PCR with six primer sets specific for CD73, CD90, CD105, CD166, CD45 and β-actin allowing a gel-based differential detection of the PCR products. To determine degree of variability of MSCs populations in terms of proliferation, cell proliferation assays were performed on expanded MSCs up to the sixth passage. At each passage, the osteogenic and adipogenic differentiation potentials of MSCs were verified by culture in inductive media. RT-PCR and cytochemical analysis revealed that, despite the loss of multipotentiality during expansion, certain markers remain expressed, indicating that these markers are unlikely to be reflective of the MSC’s true ‘stem cell’ nature. Our results suggest that decrease in the expression of MSCs specific markers correlates with down-regulation of proliferation ability and differentiation efficiency of MSCs.     

Trend analysis of metabonomics and systematic review of metabonomics-derived cancer marker metabolites

In this paper, trend analyses were performed to compare the different ‘omic’ technologies and the different analytical platforms and biological matrices exploited in metabonomic studies. While common and differential marker metabolites had been identified using various analytical platforms in metabonomics, little research was directed to review and consolidate marker metabolites in each disease state. A systematic review of metabonomics-derived marker metabolites in different cancers was performed to understand the significance of metabonomics in elucidating cancer biochemistry. The biological pathways associated with the cancer marker metabolites were further correlated to the pathology of cancers. Our trend analyses indicated that metabonomic publications increased exponentially in recent years, with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography/mass spectrometry (LC/MS) being the most popular analytical platforms while blood, urine and tissue are the most commonly profiled biological matrices. Based on the consolidated cancer marker metabolites, it is reinforced that different cancers possess some common and yet distinct metabolic phenotypes, exhibiting numerous perturbed biochemical pathways related to their needs to support cell growth and proliferation and facilitate cancer cell survival.     

Resource allocation to reproduction in animals

The standard Dynamic Energy Budget (DEB) model assumes that a fraction κ of mobilised reserve is allocated to somatic maintenance plus growth, while the rest is allocated to maturity maintenance plus maturation (in embryos and juveniles) or reproduction (in adults). All DEB parameters have been estimated for 276 animal species from most large phyla and all chordate classes. The goodness of fit is generally excellent. We compared the estimated values of κ with those that would maximise reproduction in fully grown adults with abundant food. Only 13% of these species show a reproduction rate close to the maximum possible (assuming that κ can be controlled), another 4% have κ lower than the optimal value, and 83% have κ higher than the optimal value. Strong empirical support hence exists for the conclusion that reproduction is generally not maximised. We also compared the parameters of the wild chicken with those of races selected for meat and egg production and found that the latter indeed maximise reproduction in terms of κ, while surface‐specific assimilation was not affected by selection. We suggest that small values of κ relate to the down‐regulation of maximum body size, and large values to the down‐regulation of reproduction. We briefly discuss the ecological context for these findings.