Biomedical subjects

Jan E Kammenga

Publications and source records attributed to Jan E Kammenga.

11 recordsLinked to original sources

PubMed2006

Mapping determinants of gene expression plasticity by genetical genomics in C. elegans.

Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 degrees C and 24 degrees C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 degrees C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity.

Animals↗

PubMed2006

Rapid adaptive divergence of life-history traits in response to abiotic stress within a natural population of a parthenogenetic nematode.

Sexual reproduction is acknowledged to facilitate adaptation to novel environments while asexual eukaryotes are often regarded as having low adaptive potential. This view has been challenged in a number of studies, but the adaptive potential of asexual populations in the field is poorly documented. We investigated the response of natural populations of the parthenogenetic nematode Acrobeloides nanus to imposed divergent selective pressures. For this purpose, we employed a replicated evolution experiment in the field. After 20 years of evolution under abiotic stress and control conditions, life-history traits were assessed in reaction norm- and reciprocal transplant experiments. Both these experiments indicated adaptive divergence within the population of A. nanus. Namely, the transplant experiment demonstrated that in the stressed soil environment, body growth rate was more reduced in the nematodes originating from the control treatment. In the reaction norm experiment, survival and reproduction were higher under test conditions corresponding to the native environment of the nematodes. The differences in the analysed traits are discussed in the context of life-history theory. Overall, our results strongly support high adaptive potential of A. nanus and suggest that population structure and distribution of asexual species is shaped by local adaptation events.

Adaptation, Physiological↗

PubMed2006

Temporal dynamics of effect concentrations.

In effect assessment the comparability and applicability of LCx and ECx values, which are calculated at single points in time during exposure, relies on the ability to perform a valid extrapolation to other time points of interest. The behavior of LCx in time has been extensively studied, and the behavior of ECx in time is expected to follow similar dynamics, as it is considered that the LCx is just a specific case of ECxs. However, most models have focused on validating the dynamics of LCx, and hardly anything is known about the time dependence of ECx for other endpoints or whether it is comparable to that of LCxs. We have created four scenarios where we study the dynamics of the ECx for different endpoints and how it is affected by the characteristics of two different compounds (carbendazim and pentachlorobenzene) and of two different life history strategies (hermaphroditic and sexually reproducing strains of Caenorhabditis elegans). The observed patterns of behavior in time of the ECx for body size and for reproduction showed unexpected dynamics that deviate considerably from that of the LCx. It was demonstrated that the temporal dynamics of ECx were very different for each particular endpoint. The shape of the ECx-time curves depends on the intrinsic characteristics of the endpoint of study, as well as on the characteristics of the compound and life history strategy of the organism. This makes extrapolation in time or between endpoints difficult and hampers the comparability of results based on this summary statistic. The interpretation of the results from toxicity tests can be improved through process-based modeling, as demonstrated on the current data set.

Animals↗

PubMed2006

Physiological modes of action of toxic chemicals in the nematode Acrobeloides nanus.

To gain a better understanding of the mechanisms through which a chemical exerts toxicity, a deeper insight is needed regarding the physiological processes that take place during a toxic stress. This issue can have important benefits for risk assessment, because it can contribute to a better interpretation of toxicity data. Here, we study the physiological mode of action of three different compounds (cadmium, carbendazim, and pentachlorobenzene) with an experimental data-based approach using whole life-cycle toxicity data from the nematode Acrobeloides nanus. We use a process-based model, based on the dynamic energy budget theory, to study the fluxes of energy related to physiological processes and their variation throughout the life cycle. With this approach, we unravel the physiological modes of action based on resource allocation, and we model the effects of the different modes of action at the population level. The mode of action of carbendazim was through a decrease in assimilation, with an additional effect on the production of reactive oxygen species (ROS). Cadmium increased the costs of growth, with an extra effect on ROS production, and pentachlorobenzene decreased assimilation. We compared the present results with those of previous studies using the nematode Caenorhabditis elegans, and we found that the modes of action for the three compounds differed from those found in A. nanus, showing that the life-history characteristics of each organism have a clear influence on the resulting modes of action. This highlights the importance of the interactions between a chemical and the biological characteristics of the organism in determination of the resulting physiological modes of action.

Animals↗

PubMed2005

Significance testing of synergistic/antagonistic, dose level-dependent, or dose ratio-dependent effects in mixture dose-response analysis.

In ecotoxicology, the state of the art for effect assessment of chemical mixtures is through multiple dose-response analysis of single compounds and their combinations. Investigating whether such data deviate from the reference models of concentration addition and/or independent action to identify overall synergism or antagonism is becoming routine. However, recent data show that more complex deviation patterns, such as dose ratio-dependent deviation and dose level-dependent deviation, need to be addressed. For concentration addition, methods to detect such deviation patterns exist, but they are stand-alone methods developed separately in literature, and conclusions derived from these analyses are therefore difficult to compare. For independent action, hardly any methods to detect such deviations from this reference model exist. This paper describes how these well-established mixture toxicity principles have been incorporated in a coherent data analysis procedure enabling detection and quantification of dose level-and dose ratio-specific synergism or antagonism from both the concentration addition and the independent action models. Significance testing of which deviation pattern describes the data best is carried out through maximum likelihood analysis. This analysis procedure is demonstrated through various data sets, and its applicability and limitations in mixture research are discussed.

Animals↗

PubMed2004

Pedological characterisation of sites along a transect from a primary cadmium/lead/zinc smelting works.

A pedological characterisation of seven sites along a transect from a smelter at Avonmouth, UK, was undertaken. Site locations comprised a mixture of both grassland (5 sites) and oak tree dominated (2 sites) areas. Geographically, sites were either low lying or on adjacent elevated ground. Across the transect, a severe gradient of metal concentrations was found with highest values for organic soil horizons from close to the factory. Comparisons with quality standards indicate that these metal levels are likely to be a major ecological stressor. In addition to the strong metal gradient, a number of other between site differences were also observed. These were firstly water regime, which at the low lying sites close to the smelter showed influence by both, groundwater and stagnant water, while at more distant sites indicated susceptibility to stagnant water only, and secondly soil pH, which showed large between site variations, although no consistent trend along the transect. Humus forms at sites more than 1.5 km from the smelter were characteristic for the soil conditions and land-use present, while those at sites within 1.5 km showed disturbed profiles. Indeed, the humus types present at these locations suggest that the activity of soil invertebrates may be inhibited. This is almost certainly due primarily to the high concentrations of metals that were present in mineral soil and organic horizons at the sites. However, the potential influences of water regime and pH could also be relevant factors influencing the results of any further studies conducted at these study sites.

Cadmium↗

PubMed2004

Stress proteins (hsp70, hsp60) induced in isopods and nematodes by field exposure to metals in a gradient near Avonmouth, UK.

Heat shock proteins (hsps) are potential biomarkers for monitoring environmental pollution. In this study, the use of hsps as biomarkers in field bioassays was evaluated in terrestrial invertebrates exposed to a metal gradient near Avonmouth, UK. We investigated the hsp70 response in resident and transplanted isopods of the species Oniscus asellus and Porcellio scaber and the hsp60 response in transplanted nematodes of the species Plectus acuminatus in six field sites along the metal gradient. Considerable differences were detected in the stress responses between nematodes and isopods (isopods responded in a gradient-specific manner, nematodes did not), the two isopod species and the transplanted and resident specimens of each isopod species: in the sites closest to the smelter, O. asellus residents showed high hsp70 levels while O. asellus transplanted from an unpolluted site displayed comparatively low hsp70 levels. For P. scaber, it was just the opposite. In resident isopod populations of both species, tolerant phenotypes were revealed in the most contaminated field sites. The hsp70 level in both isopod species was a suitable biomarker of effect (but of exposure only in non-tolerant individuals) even in long-term metal-contaminated field sites. The hsp60 response in the nematode alone was not a suitable biomarker for heavily contaminated soils. However, it had indicative value when related to the hsp70 response in the isopods and could be a suitable biomarker for less heavily contaminated soils.

Animals↗

PubMed2004

Critical analysis of soil invertebrate biomarkers: a field case study in Avonmouth, UK.

During the period 1996-1999 a joint field research programme (BIOPRINT-II) funded by the European Union was undertaken. The main objective of this project was the deployment of biochemical fingerprint techniques of soil invertebrate biomarkers for assessing the exposure and effect of toxicants on soil invertebrates in the field. The aim was to apply these techniques in the field focusing on a a chronically polluted field near a lead and zinc smelter in Avonmouth (UK). Therefore six sites were selected from which organisms were either sampled or transplanted to or from the laboratory. The project has provided a unique opportunity to apply a series of biological test methodologies in order to determine the hazard posed to soil sustainability and by inference soil biodiversity and function. This work has attempted to understand the linkage between effects measured at the molecular or cellular level and relate these to changes at higher levels of biological organisation. Here we evaluated the links between biomarkers and soil function parameters. The paper aims to summarize and explore the necessary caveats that must be understood before soil biomarker test systems may be used to strengthen the risk assessment process.

Animals↗

PubMed2004

Toxicity of simple mixtures to the nematode Caenorhabditis elegans in relation to soil sorption.

Single and combined toxicity of copper-zinc, copper-cadmium, cadmium-lead, copper-carbendazim, and copper-carbendazimiprodione to the nematode Caenorhabditis elegans in soil was studied. The one-week population increase was estimated as the toxicity endpoint. The aim was to study the relationship between mixture interactions in the soil and the combined toxic effect. Soil sorption was quantified using the Freundlich adsorption constant. Joint toxicity patterns were quantified by comparing mixture effects to the effect of individual constituents and were related to total metal concentrations in the soil, water-soluble concentrations, and 0.01 M CaCl2-extractable concentrations. The metal with the highest adsorption constant influenced the sorption of metal with the lowest adsorption constant when both were combined, indicating interaction. Consequently, both the composition of the mixture as well as the relative toxicity of individual mixture constituents differed between total, water-soluble, and CaCl2-extractable concentrations, which was taken into account in the data quantification procedure that was applied. Both the additive and the independent model were generally inadequate to describe the effects of metal mixtures. Compared to the additive model, synergism was observed at dose levels higher than the median effect isobole. A general relationship between mixture interactions in the soil and the combined toxicity was not found.

Adsorption↗

PubMed2004

Toxicity of binary mixtures of cadmium-copper and carbendazim-copper to the nematode Caenorhabditis elegans.

For ecological risk assessment, the additive model may be used to empirically predict toxic mixture effects. Detailed toxicity tests were performed to determine whether effects of mixtures of copper-cadmium and copper-carbendazim on Caenorhabditis elegans were similar to the effects of the individual compounds. Effects on the course of reproduction, the length of the juvenile period, the length of the reproductive period, and body length were analyzed. Dose-response data were compared to the additive model and tested for four deviation patterns from additivity: No deviation, synergistic/antagonistic deviation, dose ratio-dependent deviation, dose level-dependent deviation. During the exposure, the cadmium-copper effect on reproduction changed from a synergistic, to a dose ratio-dependent deviation from additivity. More cadmium in the mixture decreased the toxicity and more copper increased the toxicity. The effect of copper-carbendazim on reproduction was synergistic at low dose levels and antagonistic at high dose levels and independent of time. Mixture effects on the juvenile and reproductive period were similar to single component effects. It was concluded that the observed time-dependence of toxic interactions was small and that interactions on the timing of reproduction were not found. The additive model underestimated mixture effects on reproduction and body length.

Animals↗

PubMed2003

Quantifying copper and cadmium impacts on intrinsic rate of population increase in the terrestrial oligochaete Lumbricus rubellus.

Demographic methods can translate toxicant effects on individuals into consequences for populations. To date few such studies have been conducted with longer-lived invertebrates. This is because full life-cycle experiments are difficult with such species. Here we report the effects of copper and cadmium on the key demographic parameter intrinsic rate of population increase (r) in a long-lived invertebrate (an earthworm). The approach used to derive r was based on robust measurement of effects on life-cycle traits in three specifically designed toxicity tests and integration of this data within a demographic model. The three laboratory tests used to generate values for specific life-cycle parameters under copper and cadmium exposure were suited to the task. Significant effects on a range of separate adult and juvenile life-cycle parameters were seen. Integration of parameter values within the demographic equation indicated that for copper, r was reduced only at a concentration that also caused adult mortality. For cadmium, a more graded exposure-dependent effect on fitness was seen, with r reduced at sublethal concentrations. The concentration response patterns for r found for the two metals suggest significantly different consequences for earthworm populations exposed to sublethal levels of copper and cadmium.

Animals↗