Variation in infectivity and aggressiveness in space and time in wild host-pathogen systems: causes and consequences

Variation in host resistance and in the ability of pathogens to infect and grow (i.e. pathogenicity) is important as it provides the raw material for antagonistic (co)evolution and therefore underlies risks of disease spread, disease evolution and host shifts. Moreover, the distribution of this variation in space and time may inform us about the mode of coevolutionary selection (arms race vs. fluctuating selection dynamics) and the relative roles of G × G interactions, gene flow, selection and genetic drift in shaping coevolutionary processes. Although variation in host resistance has recently been reviewed, little is known about overall patterns in the frequency and scale of variation in pathogenicity, particularly in natural systems. Using 48 studies from 30 distinct host–pathogen systems, this review demonstrates that variation in pathogenicity is ubiquitous across multiple spatial and temporal scales. Quantitative analysis of a subset of extensively studied plant–pathogen systems shows that the magnitude of within‐population variation in pathogenicity is large relative to among‐population variation and that the distribution of pathogenicity partly mirrors the distribution of host resistance. At least part of the variation in pathogenicity found at a given spatial scale is adaptive, as evidenced by studies that have examined local adaptation at scales ranging from single hosts through metapopulations to entire continents and – to a lesser extent – by comparisons of pathogenicity with neutral genetic variation. Together, these results support coevolutionary selection through fluctuating selection dynamics. We end by outlining several promising directions for future research.     

Parvalbumin in mouse muscle in vivo and in vitro

Parvalbumin is a cytosolic calcium-binding protein found in adult fast-twitch mammalian muscle. Using an antibody to paravalbumin, we have shown that its distribution in adult mouse muscles is associated with certain fibre types. It is absent from slow-twitch type 1 fibres, is absent or at low levels in fast-twitch type 2A fibres, but is present at moderate or high levels in fast-twitch type 2B fibres. When adult mouse muscle is cultured with embryonic mouse spinal cord, the regenerated fibres become innervated, express the adult fast isoform of myosin heavy chain and appear histochemically as fast-twitch fibres. We therefore investigated whether these apparently mature fibres also contained parvalbumin. Parvalbumin was not found in any fibres of twenty mature cultures, suggesting that neurotrophic activity in the absence of specific adult nerve activity patterns was insufficient to cause the expression of parvalbumin in the cultures.     

Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

Neuropeptide Y (NPY) is one the most potent orexigenic peptides found in the brain. It stimulates food intake with a preferential effect on carbohydrate intake. It decreases latency to eat, increases motivation to eat and delays satiety by augmenting meal size. The effects on feeding are mediated through at least two receptors, the Y1 and Y5 receptors. The NPY system for feeding regulation is mostly located in the hypothalamus. It is formed of the arcuate nucleus (ARC), where the peptide is synthesized, and the paraventricular (PVN), dorsomedial (DMN) and ventromedial (VMN) nuclei and perifornical area where it is active. This activity is modulated by the hindbrain and limbic structures. It is dependent on energy availability, e.g. upregulation with food deprivation or restriction, and return to baseline with refeeding. It is also sensitive to diet composition with variable effects of carbohydrates and fats. Leptin signalling and glucose sensing which are directly linked to diet type are the most important factors involved in its regulation. Absence of leptin signalling in obesity models due to gene mutation either at the receptor level, as in the Zucker rat, the Koletsky rat or the db/db mouse, or at the peptide level, as in ob/ob mouse, is associated with increased mRNA abundance, peptide content and/or release in the ARC or PVN. Other genetic obesity models, such as the Otsuka-Long-Evans-Tokushima Fatty rat, the agouti mouse or the tubby mouse, are characterized by a diminution in NPY expression in the ARC nucleus and by a significant increase in the DMN. Further studies are necessary to determine the exact role of NPY in these latter models. Long-term exposure to high-fat or high-energy palatable diets leads to the development of adiposity and is associated with a decrease in hypothalamic NPY content or expression, consistent with the existence of a counter-regulatory mechanism to diminish energy intake and limit obesity development. On the other hand, an overactive NPY system (increased mRNA expression in the ARC associated with an upregulation of the receptors) is characteristic of rats or rodent strains sensitive to dietary-induced obesity. Finally, NPY appears to play an important role in body weight and feeding regulation, and while it does not constitute the only target for drug treatment of obesity, it may nevertheless provide a useful target in conjunction with others.     

Protein folding and binding in confined spaces and in crowded solutions

Simple theoretical models are presented to illustrate the effects of spatial confinement and macromolecular crowding on the equilibria and rates of protein folding and binding. Confinement is expected to significantly stabilize the folded state, but for crowding only a marginal effect on protein stability is expected. In confinement the unfolded chain is restricted to a cage but in crowding the unfolded chain may explore different interstitial voids. Because confinement and crowding eliminate the more expanded conformations of the unfolded state, folding from the compact unfolded state is expected to speed up. Crowding will shift the binding equilibrium of proteins toward the bound state. The significant slowing down in protein diffusion by crowding, perhaps beneficial for chaperonin action, could result in a decrease in protein binding rates.     

Intrinsic curvature in normal and inverted lipid structures and in membranes.

The intrinsic or spontaneous radius of curvature, R(o), of lipid monolayer assemblies is expressed in terms of a lipid molecular packing parameter, V/AI, for various geometries. It is shown that the equivalent lipid length, 1, in inverted hexagonal (HII) phases, defined by a cylindrical shell of equal total lipid volume, yields an expression for R o identical to that for inverted cylindrical micelles (or, equivalently, HII phases in the presence of excess hydrocarbon). This identity is used to obtain values of the effective packing parameter for various phosphatidylethanolamines. The temperature dependence of the intrinsic radius of curvature is predicted to be negative and to be considerably greater than that for the lipid length in nearly all cases. The thermal expansion coefficient is not constant but is found to vary, depending on the value of the lipid packing parameter. A possible addition rule is constructed for the intrinsic radius of curvature of lipid mixtures, based on the linear additivity of the effective molecular volumes, V, and molecular areas, A. This relation is found to hold for mixtures of dioleoyl phosphatidylcholine (DOPC) with dioleoyl phosphatidylethanolamine, and a value of R(o) of > or = 9 A (V/AI = 1.08) is obtained for DOPC. The energetics of the intrinsic curvature and lamellar-nonlamellar transitions are also discussed within the framework of the model.     

MPD and DNA Bending in Crystals and in Solution

Bending of 15 to 24° is observed within crystal structures ofB-DNA duplexes, is strongly sequence-dependent, and exhibits no correlation with the concentration of MPD (2-methyl-2,4-pentanediol) in the crystallizing solution. Two types of bends are observed: facultative bends or flexible hinges at junctions between regions of G·C and A·T base-pairs, and a persistent and almost obligatory bend at the center of the sequence R-G-C-Y. Only A-tracts are characteristically straight and unbent in every crystal structure examined to date. A detailed examination of normal vector plots for individual strands of a double helix provides an explanation, in terms of the stacking properties of guanine and adenine bases. The effect of high MPD concentrations, in both solution and crystal, is to decrease local bending somewhat without removing it altogether. MPD gel retardation experiments provide no basis for choosing among the three models that seek to explain macroscopic curvature of DNA by means of microscopic bending: junction bending, bent A-tracts, or bent general- sequence DNA. Crystallographic data on the straightness of A-tracts, the bendability of non-A sequences, and the identity of inclination angles in A-tract and non-A-tractB-DNA support only the general-sequence bending model. The pre-melting transition observed in A-tract DNA probably represents a relaxation of stiff adenine stacks to a flexible conformation more typical of general-sequence DNA.     

Oxytocinase in Plasma and Placenta in Normal and Prolonged Labour

In prolonged labour (dystocia) the level of activity of the enzyme oxytocinase is increased in the plasma and decreased in the placenta; the ratio of its activity in the placenta to that in plasma is less than half that found in normal labour. A possible explanation is that oxytocinase is derived mainly from the placenta and that during prolonged labour the enzyme escapes into the maternal blood stream.     

Purpurogallin--a natural and effective hepatoprotector in vitro and in vivo.

Purpurogallin is a plant phenol that is sometimes added as an oxidation retardant to fats-oils or to certain fuels or lubricants. However, it was unknown if purpurogallin is cytoprotective. Here we examined this issue, both in isolated hepatocytes and in vivo. From 0.5 to 2.0 mM, purpurogallin prolongs survival of rat hepatocytes substantially against oxyradicals generated with xanthine oxidase and hypoxanthine. The protection was dose dependent and surpassed that given by such antioxidants as ascorbate, mannitol, superoxide dismutase, catalase, and Trolox, when each was examined at or near its optimal concentration in the same system. When 1.5, 3, and 6 mumol of purpurogallin in saline were infused into rats with postischemic livers shortly before reperfusion, the mean hepatic salvages were 42, 76, and 86%, respectively. Such salvage effects would rank purpurogallin highly among the hepatoprotectors known. Over the range of 31 to 500 microM, purpurogallin inhibited the rate of O2 consumption in the xanthine oxidase reaction by approximately 90%, which was 2- to several-fold higher than the inhibition elicited by allopurinol over the same concentrations. Thus, purpurogallin is an effective natural hepatoprotector that may operate partly or principally as an inhibitor of xanthine oxidase.     

Asynchronicity in root and shoot phenology in grasses and woody plants

Phenology is central to understanding vegetation response to climate change, as well as vegetation effects on plant resources, but most temporal production data is based on shoots, especially those of trees. In contrast, most production in temperate and colder regions is belowground, and is frequently dominated by grasses. We report root and shoot phenology in 7‐year old monocultures of 10 dominant species (five woody species, five grasses) in southern Canada. Woody shoot production was greatest about 8 weeks before the peak of root production, whereas grass shoot maxima preceded root maxima by 2–4 weeks. Over the growing season, woody root, and grass root and shoot production increased significantly with soil temperature. In contrast, the timing of woody shoot production was not related to soil temperature (r=0.01). The duration of root production was significantly greater than that of shoot production (grasses: 22%, woody species: 54%). Woody species produced cooler and moister soils than grasses, but growth forms did not affect seasonal patterns of soil conditions. Although woody shoots are the current benchmark for phenology studies, the other three components examined here (woody plant roots, grass shoots and roots) differed greatly in peak production time, as well as production duration. These results highlight that shoot and root phenology is not coincident, and further, that major plant growth forms differ in their timing of above‐ and belowground production. Thus, considering total plant phenology instead of only tree shoot phenology should provide a better understanding of ecosystem response to climate change.     

Polarity and form regulation in development and reconstitution

In the literature, it is often assumed, for example with respect to Hydra, that several Turing systems coexist and it is also assumed that maintaining the polar profile, even when the system increases in size, is important for the polarity of the final phenotype. It is shown here that in reality there is only one Turing system, Child's system. To obtain a complete polar individual or organ, whether in reconstitution or development, it is essential that the complete succession of metabolic patterns occurs. Child's concepts of physiological dominance, subordination and isolation are interpreted in the light of Turing theory and in particular the Turing wavelength. It is emphasised, particularly by pointing to Child's metabolic patterns in coelenterates, both in development and in reconstitution, that it is the elongation that drives the succession polar metabolic pattern-->bipolar metabolic pattern, and this corresponds to the prediction of Turing theory supporting the thesis that Child's metabolic pattern is a Turing pattern. It is shown that if we assume that ATP is the Turing inhibitor then the many results of Child about the reduction of the scale of organisation with the decrease in the intensity of the energy metabolism correspond to the reduction of the Turing wavelength. The interplay between the Turing wavelength and the length of the form explains the conditions of reconstitution under which partial forms, wholes and form regulation are obtained. It is suggested that higher metabolism is responsible for both larger size and larger Turing wavelength thus securing form regulation. The results could be of importance in modern 'regenerative biology'. Heteromorphosis, i.e. animals with two heads (or two tails), one at each end, is explained by a bipolar Turing-Child metabolic pattern replacing a polar metabolic pattern. This can be brought about by chemical or by genetic means and indeed the prediction for Drosophila that the transition, wild type-->Bicaudal D, occurs because a polar Turing pattern is replaced by bipolar Turing pattern is confirmed, again if we accept that Child's metabolic pattern is the underlying Turing pattern. Child's experiments on Drosophila, including the requirement of critical length for metabolic polarity, are explained by Turing theory. Phenocopies and phenotypes are explained by the Turing-Child theory. It is shown that both Child's results about metabolic patterns and modern results for Hydra about gap junctions, 'endogeneous inhibitor' and gene expression, are correlated and explained by (cAMP, ATP) Turing theory. It is argued that the double-gradient hypothesis is incorrect in its original formulation and that it is Child's conception of succeeding metabolic patterns that is the correct one and that it corresponds to the prediction of the Turing theory.     

Structure and evolution of Streptomyces interaction networks in soil and in silico

Soil grains harbor an astonishing diversity of Streptomyces strains producing diverse secondary metabolites. However, it is not understood how this genotypic and chemical diversity is ecologically maintained. While secondary metabolites are known to mediate signaling and warfare among strains, no systematic measurement of the resulting interaction networks has been available. We developed a high-throughput platform to measure all pairwise interactions among 64 Streptomyces strains isolated from several individual grains of soil. We acquired more than 10,000 time-lapse movies of colony development of each isolate on media containing compounds produced by each of the other isolates. We observed a rich set of such sender-receiver interactions, including inhibition and promotion of growth and aerial mycelium formation. The probability that two random isolates interact is balanced; it is neither close to zero nor one. The interactions are not random: the distribution of the number of interactions per sender is bimodal and there is enrichment for reciprocity--if strain A inhibits or promotes B, it is likely that B also inhibits or promotes A. Such reciprocity is further enriched in strains derived from the same soil grain, suggesting that it may be a property of coexisting communities. Interactions appear to evolve rapidly: isolates with identical 16S rRNA sequences can have very different interaction patterns. A simple eco-evolutionary model of bacteria interacting through antibiotic production shows how fast evolution of production and resistance can lead to the observed statistical properties of the network. In the model, communities are evolutionarily unstable--they are constantly being invaded by strains with new sets of interactions. This combination of experimental and theoretical observations suggests that diverse Streptomyces communities do not represent a stable ecological state but an intrinsically dynamic eco-evolutionary phenomenon.     

Folic acid supplementation in pregnancy and implications in health and disease

Maternal exposure to dietary factors during pregnancy can influence embryonic development and may modulate the phenotype of offspring through epigenetic programming. Folate is critical for nucleotide synthesis, and preconceptional intake of dietary folic acid (FA) is credited with reduced incidences of neural tube defects in infants. While fortification of grains with FA resulted in a positive public-health outcome, concern has been raised for the need for further investigation of unintended consequences and potential health hazards arising from excessive FA intakes, especially following reports that FA may exert epigenetic effects. The objective of this article is to discuss the role of FA in human health and to review the benefits, concerns and epigenetic effects of maternal FA on the basis of recent findings that are important to design future studies.     

Variability and size in mammals and birds

Body size, its variability, and their ecological correlates have long been important topics in evolutionary biology. Yet, the question of whether there is a general relationship between size and size-relative variability has not previously been addressed. Through an analysis of body-mass and length measurements from 65 074 individuals from 351 mammalian species, we show that size-relative variability increases significantly with mean species body size. Analysis of mean body mass and standard deviations for 237 species of birds revealed the same pattern. We present three plausible alternatives explanations and eliminate several others. Of these, the hypothesis that the increase in size-relative variability with mean body mass is related to the scaling of body mass components is most strongly supported. In effect, larger mammals and birds are more variable because their body mass is composed to greater relative degree of components with higher intrinsic variability (bone, fat, and muscle). In contrast, smaller mammals and birds have lower body mass variability because they are composed to a greater relative extent of components (viscera and nervous system) in which size variation is more highly constrained by energetic and functional factors.     

Motor reactions and vestibular reflexes in cats and monkey in weightlessness

Close morpho-functional relationships of the cerebellum and vestibular system at all stages of phylogenesis of vertebrates suggest that cerebellum can be regarded as an important center of gravireceptive function. Direct examination of electrical activity of the labyrinth in cats during transient (1-2 sec) state of weightlessness produced by free fall has shown that there was an almost two fold increase in both the rate and amplitude of electrical activity in the vestibular ganglion. It is commonly accepted at present time that the conditions of orbital flight around Earth closely connect with weightlessness that usually manifests itself as undesirable factor of flight. It is known, that vestibular, proprioceptive, visual and other sensory modalities are converted on the cerebellum, which would indicate that this information is used for motor coordination and spatial orientation. Undoubtedly, origin of many vestibulo-motor disturbances during flight and in postflight period to a considerable degree depends on weightlessness. On the whole the visual illusions, motor discoordination, and space sickness, including vomiting are referred to the "space adaptation syndrome." But nature of these disturbances still is not well understood. This investigation was dedicated to study of vestibular and motor reactions of cats and monkey in short-term microgravity.     

Proline-directed phosphorylation and isomerization in mitotic regulation and in Alzheimer's Disease

The reversible phosphorylation of proteins on serine/threonine residues preceding proline (Ser/Thr-Pro) is a major regulatory mechanism for the control of a series of cell cycle events. Although phosphorylation is thought to regulate protein function by inducing conformational changes, little is known about most of these conformational changes and their significance. Recent studies indicate that the conformation and function of a subset of these phosphorylated proteins are controlled by the prolyl isomerase Pin1 through isomerization of specific phosphorylated Ser/Thr-Pro bonds. Furthermore, compelling evidence supports the idea that proline-directed phosphorylation and subsequent isomerization play a critical role not only in cell cycle control, but also in the development of Alzheimer's disease, where postmitotic neurons display various cell cycle markers, especially mitotic events, prior to degeneration.     

Entropy and convergence in dynamics and demography

Demographic dynamics is formally equivalent to the dynamics of a Markov chain, as is true of some nonlinear dynamical systems. Convergence to demographic equilibrium can be studied in terms of convergence in the Markov chain. Tuljapurkar (1982) showed that population entropy (Kolmogorov-Sinai entropy) provides information on the rate of this convergence. This paper begins by considering finite state Markov chains, providing elementary proofs of the relationship between convergence rate and entropy, and discusses in detail the uses and limitations of entropy as a convergence measure; these results also apply to Markovian dynamical systems. Next, new qualitative and quantitative arguments are used to discuss the demographic meaning of entropy. An exact relationship is established giving population entropy in terms of the eigenvalues of the Leslie matrix characteristic equation. Finally, the significance of imprimitive and periodic limits is discussed in relation to population entropy.     

Nutations in Shoots and in Desmodium Lateral Leaflets, Nyctinastism and Seismonastism in Mimosa pudica. Comparison and Evolution of Morphology and Mechanism

Four plant movements are considered: circumnutation of apeces of Phaseolus, nutations (ultradian movement) of lateral leaflets of Desmodium gyrans, nyctinastim and Mimosa pudica seismonastic movement. The rhythms mechanisms are briefly summarized except for seismonastism: in this case, experimental evidence progressively accumulated, at first indirect and recently direct is described, leading eventually to conclusions about the existence and function of contractile proteins. Indeed, in spite of the nowadays clear evidence, the mechanism has not yet gained total recognition among plant physiologists and it is usually overseen or ignored in a reductionist approach. From these four exemplative cases, an interesting evolutionary organization change is apparent in movement, morphogenesis, chemistry and mechanism.     

Nutations in Shoots and in Desmodium Lateral Leaflets,Nyctinastism and Seismonastism in Mimosa pudica. Comparison and Evolution of Morphology and Mechanism

Four plant movements are considered: circumnutation of apeces of Phaseolus, nutations (ultradian movement) of lateral leaflets of Desmodium gyrans, nyctinastim and Mimosa pudica seismonastic movement. The rhythms mechanisms are briefly summarized except for seismonastism: in this case, experimental evidence progressively accumulated, at first indirect and recently direct is described, leading eventually to conclusions about the existence and function of contractile proteins. Indeed, in spite of the nowadays clear evidence, the mechanism has not yet gained total recognition among plant physiologists and it is usually overseen or ignored in a reductionist approach. From these four exemplative cases, an interesting evolutionary organization change is apparent in movement, morphogenesis, chemistry and mechanism.     

Hydroxycinnamates and their in vitro and in vivo antioxidant activities

Hydroxycinnamates are among the most widely distributed plant phenylpropanoids present in the free, conjugated-soluble and insoluble-bound forms. This review will focus on the occurrence, in vitro and in vivo antioxidant activities of ferulic, coumaric, caffeic and sinapic acids and their derivatives. Hydroxycinnamates are found in almost all food groups though they are abundant in cereals, legumes, oilseeds, fruits, vegetables and beverages and render antioxidant activity by scavenging hydroxyl radical, superoxide radical anion, several organic radicals, peroxyl radical, peroxinitrite and singlet oxygen, among others. Further, their antioxidant activity as chain breaking antioxidants and reducing agents is also notable. Ferulic acid and its derivatives such as ferulic acid ethyl ester, ferulic acid dehydrodimers, feruloyl glycosides and curcumin have demonstrated potent antioxidant activity in both in vitro and in vivo systems. Similarly, caffeic acid and some of its derivatives such as caffeic acid phenethyl ester, rosmarinic acid, and chlorogenic acid exhibit antioxidant activity. The highest antioxidant activity was observed for caffeic acid whereas p-coumaric acid had the least effect among major hydroxycinnamic acids. The importance of structural effects on the potency of antioxidant activity of hydroxycinnamates is discussed. While this review also shows the existence of substantial body of evidences for in vitro antioxidant activity of hydroxycinnamates, there is a clear gap for in vivo information, particularly for sinapic and p-coumaric acids and their derivatives. The role of grains, fruits, vegetables and red wine in disease risk reduction and health promotion could partly be attributed to their constituent hydroxycinnamates.