Pharmacological correction of the apoptosis level in cortical neurons of ageing HER2/neu transgenic mice

Neurodegenerative changes and neuronal death underlie ageing of the nervous system. We investigated the mechanisms of apoptosis in sensorimotor cortical neurons of HER2/neu transgenic mice during ageing, as well as the functional changes in the cortex and the involvement of exogenous neurometabolites (cytoflavin, piracetam) in the regulation of neuronal death and locomotor and psycho-emotional status in mice. The level of apoptosis and expression of the apoptotic protein markers (TUNEL, immunohistochemistry, Western blotting) were detected in HER2/neu transgenic mice versus wild type mice (FBV strain). In ageing wild type mice, the basal activity decreases while the anxiety level increases correlating with the high level of neuronal apoptosis. We revealed specific behavioral features of HER2/neu transgenic mice—their low basal activity which remains intact during ageing. Previously, we have shown that in this mouse strain the level of apoptosis is low, with no age-related dynamics, due to the suppression primarily of the p53-dependent pathway by HER2 (tyrosine kinase receptor) overexpression. Here we show that cytoflavin and piracetam have a pronounced neuroprotective effect, preserving and restoring the nervous system functions (improving locomotion and psychological status) in both mouse strains. The effect of the tested neurometabolites on neuronal apoptosis is ambiguous. In case of low-level apoptosis, there occurs its moderate stimulation in HER2/neu transgenic mice that are characterized by a high level of carcinogenesis (via the extrinsic and p53-dependent pathways with caspase-3 activation) which probably prevents tumor development. By contrast, in aged wild-type mice there is a marked decrease in the level of age-related apoptosis (via the stimulation of antiapoptotic protein Mcl-1 expression) supposed to prevent neurodegeneration.     

Changes in the Levels of Neurospecific Proteins and in Behavioral Phenomena in Rats with Hepatic Encephalopathy

We showed that, under conditions of experimental chronic hepatitis, excessive increases in the levels of a Ca-binding protein, S-100b, and a neuronal cell adhesion molecule, NCAM, occur in all parts of the brain of Wistar rats. This is accompanied by suppression of locomotor and orientational/research activity of the animals and increase in their stress sensitivity. Treatment by α ketoglutarate and cytoflavin in chronic hepatitis provides a clear neuroprotective effect.     

Parental environmental effects and cyclical dynamics in plant populations

Abstract Parental environmental effects have been widely reported in plants, but these effects are often weak relative to direct effects of current environmental conditions. Few studies have asked when consideration of such effects is necessary to understand long-term plant population dynamics. In this article, I show that inclusion of effects of parental density on offspring mass fundamentally changes population dynamics models by making recruitment a function of population size in two previous generations ([Formula: see text]), rather than one ([Formula: see text]). Models without parental density effects predict either stable population dynamics or sharp crashes from high to low population size (flip bifurcations). When parental effects are at least one-third the size of direct density effects, gradual cycles from high to low population size (Hopf bifurcations) are possible. In this study, I measured effects of parental and offspring density on offspring quality in an annual plant, Cardamine pensylvanica, by manipulating plant density independently in parent and offspring generations and by comparing the effects of parent and offspring density on offspring performance. Parental density effects were detectable but were noticeably weaker than offspring density effects. Nonetheless, the parental effect was large enough to change population dynamics predictions. Thus, parental effects may be an important component of the numerical dynamics of plant populations.     

Nitrogen and Phosphorus Release from Mixed Litter Layers is Lower than Predicted from Single Species Decay

Ecosystem-level nutrient dynamics during decomposition are often estimated from litter monocultures. If species effects are additive, we can statistically predict nutrient dynamics in multi-species systems from monoculture work, and potential consequences of species loss. However, if species effects are dependent on interactions with other litter species (that is, non-additive), predictions based on monoculture data will likely be inaccurate. We conducted a 3-year, full-factorial, mixed-litter decomposition study of four dominant tree species in a temperate forest and measured nitrogen and phosphorus dynamics to explore whether nutrient dynamics in mixtures were additive or non-additive. Following common approaches, we used litterfall data to predict nutrient dynamics at the ecosystem-level. In mixtures, we observed non-additive effects of litter mixing on nutrient dynamics: the presence of nutrient-rich species in mixture facilitated nutrient release, whereas nutrient-poor species facilitated nutrient retention. Fewer nutrients were released from mixtures containing high-quality litter, and more immobilized from mixtures containing low-quality litter, than predicted from monocultures, creating a difference in overall nutrient release between predicted and actual dynamics in litter mixtures. Nutrient release at the ecosystem-level was greatly overestimated when based on monocultures because the effect of species interactions on nutrient immobilization was not accounted for. Our data illustrate that the identity of species in mixtures is key to their role in non-additive interactions, with repercussions for mineral nutrient availability and storage. These results suggest that predictions of ecosystem-level nutrient dynamics using litter monoculture data likely do not accurately represent actual dynamics because the effects of litter species interactions are not incorporated. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Variation in foraging success among predators and its implications for population dynamics

The effects of the expected predation rate on population dynamics have been studied intensively, but little is known about the effects of predation rate variability (i.e., predator individuals having variable foraging success) on population dynamics. In this study, variation in foraging success among predators was quantified by observing the predation of the wolf spider Pardosa pseudoannulata on the cricket Gryllus bimaculatus in the laboratory. A population model was then developed, and the effect of foraging variability on predator–prey dynamics was examined by incorporating levels of variation comparable to those quantified in the experiment. The variability in the foraging success among spiders was greater than would be expected by chance (i.e., the random allocation of prey to predators). The foraging variation was density‐dependent; it became higher as the predator density increased. A population model that incorporates foraging variation shows that the variation influences population dynamics by affecting the numerical response of predators. In particular, the variation induces negative density‐dependent effects among predators and stabilizes predator–prey dynamics.     

Molecular dynamics simulations of C2F6 effects on gramicidin A: implications of the mechanisms of general anesthesia

It was recently postulated that the effects of general anesthetics on protein global dynamics might underlie a unitary molecular mechanism of general anesthesia. To verify that the specific dynamics effects caused by general anesthetics were not shared by nonanesthetic molecules, two parallel 8-ns all-atom molecular dynamics simulations were performed on a gramicidin A (gA) channel in a fully hydrated dimyristoylphosphatidylcholine membrane in the presence and absence of hexafluoroethane (HFE), which structurally resembles the potent anesthetic molecule halothane but produces no anesthesia. Similar to halothane, HFE had no measurable effects on the gA channel structure. In contrast to halothane, HFE produced no significant changes in the gA channel dynamics. The difference between halothane and HFE on channel dynamics can be attributed to their distinctly different distributions within the lipid bilayer and consequently to the different interactions of the anesthetic and the nonanesthetic molecules with the channel-anchoring tryptophan residues. The study further supports the notion that anesthetic-induced changes in protein global dynamics may play an important role in mediating anesthetic actions on proteins.     

Linking extinction-colonization dynamics to genetic structure in a salamander metapopulation

Theory predicts that founder effects have a primary role in determining metapopulation genetic structure. However, ecological factors that affect extinction-colonization dynamics may also create spatial variation in the strength of genetic drift and migration. We tested the hypothesis that ecological factors underlying extinction-colonization dynamics influenced the genetic structure of a tiger salamander (Ambystoma tigrinum) metapopulation. We used empirical data on metapopulation dynamics to make a priori predictions about the effects of population age and ecological factors on genetic diversity and divergence among 41 populations. Metapopulation dynamics of A. tigrinum depended on wetland area, connectivity and presence of predatory fish. We found that newly colonized populations were more genetically differentiated than established populations, suggesting that founder effects influenced genetic structure. However, ecological drivers of metapopulation dynamics were more important than age in predicting genetic structure. Consistent with demographic predictions from metapopulation theory, genetic diversity and divergence depended on wetland area and connectivity. Divergence was greatest in small, isolated wetlands where genetic diversity was low. Our results show that ecological factors underlying metapopulation dynamics can be key determinants of spatial genetic structure, and that habitat area and isolation may mediate the contributions of drift and migration to divergence and evolution in local populations.     

Habitat fragmentation, variable edge effects, and the landscape-divergence hypothesis

Edge effects are major drivers of change in many fragmented landscapes, but are often highly variable in space and time. Here we assess variability in edge effects altering Amazon forest dynamics, plant community composition, invading species, and carbon storage, in the world's largest and longest-running experimental study of habitat fragmentation. Despite detailed knowledge of local landscape conditions, spatial variability in edge effects was only partially foreseeable: relatively predictable effects were caused by the differing proximity of plots to forest edge and varying matrix vegetation, but windstorms generated much random variability. Temporal variability in edge phenomena was also only partially predictable: forest dynamics varied somewhat with fragment age, but also fluctuated markedly over time, evidently because of sporadic droughts and windstorms. Given the acute sensitivity of habitat fragments to local landscape and weather dynamics, we predict that fragments within the same landscape will tend to converge in species composition, whereas those in different landscapes will diverge in composition. This 'landscape-divergence hypothesis', if generally valid, will have key implications for biodiversity-conservation strategies and for understanding the dynamics of fragmented ecosystems.     

Variability in primary productivity determines metapopulation dynamics

Temporal variability in primary productivity can change habitat quality for consumer species by affecting the energy levels available as food resources. However, it remains unclear how habitat-quality fluctuations may determine the dynamics of spatially structured populations, where the effects of habitat size, quality and isolation have been customarily assessed assuming static habitats. We present the first empirical evaluation on the effects of stochastic fluctuations in primary productivity—a major outcome of ecosystem functions—on the metapopulation dynamics of a primary consumer. A unique 13-year dataset from an herbivore rodent was used to test the hypothesis that inter-annual variations in primary productivity determine spatiotemporal habitat occupancy patterns and colonization and extinction processes. Inter-annual variability in productivity and in the growing season phenology significantly influenced habitat colonization patterns and occupancy dynamics. These effects lead to changes in connectivity to other potentially occupied habitat patches, which then feed back into occupancy dynamics. According to the results, the dynamics of primary productivity accounted for more than 50% of the variation in occupancy probability, depending on patch size and landscape configuration. Evidence connecting primary productivity dynamics and spatiotemporal population processes has broad implications for metapopulation persistence in fluctuating and changing environments.     

Extinction–immigration dynamics lag behind environmental filtering in shaping the composition of tropical dry forests within a changing landscape

The impact of rapid habitat loss and fragmentation on biodiversity is a major issue. However, we still lack an integrative understanding of how these changes influence biodiversity dynamics over time. In this study, we investigate the effects of these changes in terms of both niche-based and neutral dynamics. We hypothesize that habitat loss has delayed effects on neutral immigration–extinction dynamics, while edge effects and environmental heterogeneity in habitat patches have rapid effects on niche-based dynamics. We analyzed taxonomic and functional composition of 100 tree communities in a tropical dry forest landscape of New-Caledonia subject to habitat loss and fragmentation. We designed an original, process-based simulation framework, and performed Approximate Bayesian Computation to infer the influence of niche-based and neutral processes. Then, we performed partial regressions to evaluate the relationships between inferred parameter values of communities and landscape metrics (distance to edge, patch area, and habitat amount around communities), derived from either recent or past (65 yr ago) aerial photographs, while controlling for the effect of soil and topography. We found that landscape structure influences both environmental filtering and immigration. Immigration rate was positively related to past habitat amount surrounding communities. In contrast, environmental filtering was mostly affected by present landscape structure and mainly influenced by edge vicinity and topography. Our results highlight that landscape changes have contrasting spatio-temporal influences on niche-based and neutral assembly dynamics. First, landscape-level habitat loss and community isolation reduce immigration and increase demographic stochasticity, resulting in slow decline of local species diversity and extinction debt. Second, recent edge creation affects environmental filtering, incurring rapid changes in community composition by favoring species with edge-adapted strategies. Our study brings new insights about temporal impacts of landscape changes on biodiversity dynamics. We stress that landscape history critically influences these dynamics and should be taken into account in conservation policies.     

Self-organizing dominance hierarchies in a wild primate population

Linear dominance hierarchies, which are common in social animals, can profoundly influence access to limited resources, reproductive opportunities and health. In spite of their importance, the mechanisms that govern the dynamics of such hierarchies remain unclear. Two hypotheses explain how linear hierarchies might emerge and change over time. The ‘prior attributes hypothesis’ posits that individual differences in fighting ability directly determine dominance ranks. By contrast, the ‘social dynamics hypothesis’ posits that dominance ranks emerge from social self-organization dynamics such as winner and loser effects. While the prior attributes hypothesis is well supported in the literature, current support for the social dynamics hypothesis is limited to experimental studies that artificially eliminate or minimize individual differences in fighting abilities. Here, we present the first evidence supporting the social dynamics hypothesis in a wild population. Specifically, we test for winner and loser effects on male hierarchy dynamics in wild baboons, using a novel statistical approach based on the Elo rating method for cardinal rank assignment, which enables the detection of winner and loser effects in uncontrolled group settings. Our results demonstrate (i) the presence of winner and loser effects, and (ii) that individual susceptibility to such effects may have a genetic basis. Taken together, our results show that both social self-organization dynamics and prior attributes can combine to influence hierarchy dynamics even when agonistic interactions are strongly influenced by differences in individual attributes. We hypothesize that, despite variation in individual attributes, winner and loser effects exist (i) because these effects could be particularly beneficial when fighting abilities in other group members change over time, and (ii) because the coevolution of prior attributes and winner and loser effects maintains a balance of both effects.     

The Self-Limiting Dynamics of TGF-β Signaling In Silico and In Vitro,with Negative Feedback through PPM1A Upregulation

The TGF-β/Smad signaling system decreases its activity through strong negative regulation. Several molecular mechanisms of negative regulation have been published, but the relative impact of each mechanism on the overall system is unknown. In this work, we used computational and experimental methods to assess multiple negative regulatory effects on Smad signaling in HaCaT cells. Previously reported negative regulatory effects were classified by time-scale: degradation of phosphorylated R-Smad and I-Smad-induced receptor degradation were slow-mode effects, and dephosphorylation of R-Smad was a fast-mode effect. We modeled combinations of these effects, but found no combination capable of explaining the observed dynamics of TGF-β/Smad signaling. We then proposed a negative feedback loop with upregulation of the phosphatase PPM1A. The resulting model was able to explain the dynamics of Smad signaling, under both short and long exposures to TGF-β. Consistent with this model, immuno-blots showed PPM1A levels to be significantly increased within 30 min after TGF-β stimulation. Lastly, our model was able to resolve an apparent contradiction in the published literature, concerning the dynamics of phosphorylated R-Smad degradation. We conclude that the dynamics of Smad negative regulation cannot be explained by the negative regulatory effects that had previously been modeled, and we provide evidence for a new negative feedback loop through PPM1A upregulation. This work shows that tight coupling of computational and experiments approaches can yield improved understanding of complex pathways.     

Disentangling demographic co‐effects of predation and pollution on population dynamics

In nature species react to a variety of endogenous and exogenous ecological factors. Understanding the mechanisms by which these factors interact and drive population dynamics is a need for understanding and managing ecosystems. In this study we assess, using laboratory experiments, the effects that the combinations of two exogenous factors exert on the endogenous structure of the population dynamics of a size‐structured population of Daphnia. One exogenous factor was size‐selective predation, which was applied on experimental populations through simulating: 1) selective predation on small prey, 2) selective predation on large prey and 3) non‐selective predation. The second exogenous factor was pesticide exposure, applied experimentally in a quasi‐continuous regime. Our analysis combined theoretical models and statistical testing of experimental data for analyzing how the density dependence structure of the population dynamics was shifted by the different exogenous factors. Our results showed that pesticide exposure interacted with the mode of predation in determining the endogenous dynamics. Populations exposed to the pesticide and to either selective predation on newborns or selective predation on adults exhibited marked nonlinear effects of pesticide exposure. However, the specific mechanisms behind such nonlinear effects were dependent on the mode of size‐selectivity. In populations under non‐selective predation the pesticide exposure exerted a weak lateral effect. The ways in which endogenous process and exogenous factors may interact determine population dynamics. Increases in equilibrium density results in higher variance of population fluctuations but do not modify the stability properties of the system, while changes in the maximum growth rate induce changes in the dynamic regimes and stability properties of the population. Future consideration for research includes the consequences of the seasonal variation in the composition and activity of the predator assembly in interaction with the seasonal variation in exposure to agrochemicals on freshwater population dynamics.     

Temperature, growth and dietary effects on fish mercury dynamics in two Ontario lakes

A bioenergetics-based model was used to investigate the effects of temperature, growth and dietary exposure on methylmercury dynamics in walleye (Stizostedion vitreum) and yellow perch (Perca flavescens) from two lakes sampled in northwestern Ontario. Orange Lake was smaller, warmer, had slower fish growth and higher mercury concentrations in yearling yellow perch and walleye (three fold difference in 40 cm walleye) than Trout Lake. The model was applied to test the hypothesis that higher water temperatures in Orange Lake increased metabolic needs, food consumption and mercury uptake in fish. The effects of different growths rates in the lakes were also considered. Temperature/metabolic effects and growth effects on internal methylmercury dynamics in walleye and perch were predicted to occur but be of secondary importance. Different dietary exposure to methylmercury was likely the dominant source of variation in fish mercury concentrations between the two lakes.     

Impact of dispersal on population growth: the role of inter-patch distance

Dispersal can play a key role in the dynamics of patchy populations through patch colonization, and generally this leads to distance-dependent colonization. Less recognised are the roles of dispersal and inter-patch distance on the growth of a population after colonization. We use a laboratory mite model system in which both juveniles and adults can disperse to explore the impact of dispersal, and particularly inter-patch distance, on population dynamics. We examine the dynamics of patches after colonization by manipulating the presence of a dispersal corridor to a source patch at two inter-patch distances. Consistent with many field studies, the results show colonization was slower in more distant patches. Following colonization, the effect of the dispersal corridor on dynamics was dependent on inter-patch distance. In patches near the source, the number of adults tended to increase at a faster rate, and juveniles at a slower rate when connected with a dispersal corridor. In contrast, adult numbers grew slower and juveniles tended to grow faster when connected with a corridor in more distant patches. In the long-term, equilibrium adult numbers were lower in patches connected to the source patch at both distances. These results are likely to be driven by the effects of inter-patch distance on dispersal mortality, and the effects of dispersal on patch abundance and within-patch competition. These results confirm that distance is important for patch colonization and also show that distance can affect population density after colonization. The effects of dispersal and distance on local dynamics could be important in the dynamics of patchy populations in increasingly fragmented landscapes.     

Reconstructing Local Population Dynamics in Noisy Metapopulations—The Role of Random Catastrophes and Allee Effects

Reconstructing the dynamics of populations is complicated by the different types of stochasticity experienced by populations, in particular if some forms of stochasticity introduce bias in parameter estimation in addition to error. Identification of systematic biases is critical when determining whether the intrinsic dynamics of populations are stable or unstable and whether or not populations exhibit an Allee effect, i.e., a minimum size below which deterministic extinction should follow. Using a simulation model that allows for Allee effects and a range of intrinsic dynamics, we investigated how three types of stochasticity—demographic, environmental, and random catastrophes— affect our ability to reconstruct the intrinsic dynamics of populations. Demographic stochasticity aside, which is only problematic in small populations, we find that environmental stochasticity—positive and negative environmental fluctuations—caused increased error in parameter estimation, but bias was rarely problematic, except at the highest levels of noise. Random catastrophes, events causing large-scale mortality and likely to be more common than usually recognized, caused immediate bias in parameter estimates, in particular when Allee effects were large. In the latter case, population stability was predicted when endogenous dynamics were actually unstable and the minimum viable population size was overestimated in populations with small or non-existent Allee effects. Catastrophes also generally increased extinction risk, in particular when endogenous Allee effects were large. We propose a method for identifying data points likely resulting from catastrophic events when such events have not been recorded. Using social spider colonies (Anelosimus spp.) as models for populations, we show that after known or suspected catastrophes are accounted for, reconstructed growth parameters are consistent with intrinsic dynamical instability and substantial Allee effects. Our results are applicable to metapopulation or time series data and are relevant for predicting extinction in conservation applications or the management of invasive species.     

How predator functional responses and Allee effects in prey affect the paradox of enrichment and population collapses

In Rosenzweig-MacArthur models of predator-prey dynamics, Allee effects in prey usually destabilize interior equilibria and can suppress or enhance limit cycles typical of the paradox of enrichment. We re-evaluate these conclusions through a complete classification of a wide range of Allee effects in prey and predator's functional response shapes. We show that abrupt and deterministic system collapses not preceded by fluctuating predator-prey dynamics occur for sufficiently steep type III functional responses and strong Allee effects (with unstable lower equilibrium in prey dynamics). This phenomenon arises as type III functional responses greatly reduce cyclic dynamics and strong Allee effects promote deterministic collapses. These collapses occur with decreasing predator mortality and/or increasing susceptibility of the prey to fall below the threshold Allee density (e.g. due to increased carrying capacity or the Allee threshold itself). On the other hand, weak Allee effects (without unstable equilibrium in prey dynamics) enlarge the range of carrying capacities for which the cycles occur if predators exhibit decelerating functional responses. We discuss the results in the light of conservation strategies, eradication of alien species, and successful introduction of biocontrol agents.     

Environmental fluctuations restrict eco-evolutionary dynamics in predator–prey system

Environmental fluctuations, species interactions and rapid evolution are all predicted to affect community structure and their temporal dynamics. Although the effects of the abiotic environment and prey evolution on ecological community dynamics have been studied separately, these factors can also have interactive effects. Here we used bacteria–ciliate microcosm experiments to test for eco-evolutionary dynamics in fluctuating environments. Specifically, we followed population dynamics and a prey defence trait over time when populations were exposed to regular changes of bottom-up or top-down stressors, or combinations of these. We found that the rate of evolution of a defence trait was significantly lower in fluctuating compared with stable environments, and that the defence trait evolved to lower levels when two environmental stressors changed recurrently. The latter suggests that top-down and bottom-up changes can have additive effects constraining evolutionary response within populations. The differences in evolutionary trajectories are explained by fluctuations in population sizes of the prey and the predator, which continuously alter the supply of mutations in the prey and strength of selection through predation. Thus, it may be necessary to adopt an eco-evolutionary perspective on studies concerning the evolution of traits mediating species interactions.     

Density dependence in group dynamics of a highly social mongoose, Suricata suricatta

1.?For social species, the link between individual behaviour and population dynamics is mediated by group-level demography. 2.?Populations of obligate cooperative breeders are structured into social groups, which may be subject to inverse density dependence (Allee effects) that result from a dependence on conspecific helpers, but evidence for population-wide Allee effects is rare. 3.?We use field data from a long-term study of cooperative meerkats (Suricata suricatta; Schreber, 1776) - a species for which local Allee effects are not reflected in population-level dynamics - to empirically model interannual group dynamics. 4.?Using phenomenological population models, modified to incorporate environmental conditions and potential Allee effects, we first investigate overall patterns of group dynamics and find support only for conventional density dependence that increases after years of low rainfall. 5.?To explain the observed patterns, we examine specific demographic rates and assess their contributions to overall group dynamics. Although per-capita meerkat mortality is subject to a component Allee effect, it contributes relatively little to observed variation in group dynamics, and other (conventionally density dependent) demographic rates - especially emigration - govern group dynamics. 6.?Our findings highlight the need to consider demographic processes and density dependence in subpopulations before drawing conclusions about how behaviour affects population processes in socially complex systems.     

Indirect effects and spatial scaling affect the persistence of multispecies metapopulations

Quantifying the role of space and spatial scale on the population dynamics of ecological assemblages is a contemporary challenge in ecology. Here, we evaluate the role of metapopulation dynamics on the persistence and dynamics of a multispecies predator-prey assemblage where two prey species shared a common natural enemy (apparent competition). By partitioning the effects of increased resource availability from the effects of metapopulation structure on regional population persistence we show that space has a marked impact on the dynamics of apparent competition in multispecies predator-prey assemblages. Further, the role of habitat size and stochasticity are also shown to influence the dynamics and persistence of this multispecies interaction. The broader consequences of these processes are discussed.