Trace Metal Mixture Toxicity in Aquatic Organism Reviewed from a Biotoxicity Perspective

Biotoxicity of individual metals is well investigated but that of metal mixture, an environmental reality, in the developing metal mixture, is relatively obscure. Experimental evidences had shown that this mixture could give rise to combined effects that were different from the effect of metals one by one. This review provides an overview of recent research on metal mixture toxicity and the methods employed to predict their toxic combined effects. The two established reference models, the concentration-addition model and the independent-addition model, were used for evaluating the combined effect from the biological activities of the metal mixtures. While the reference models had provided reasonable tools for analyzing the combined effects, the actual predictions for binary metal mixtures showed often somewhat less than additive combined effects compared to what has been observed. As the metal bioavailability is oriented by several environmental factors as well as the toxicodynamics of metals is highly compound-specific, the non-interactive combined effects may be confused with different processes of the interactions. Thus, for improving the predictability of combined effects in metal mixture toxicity, numerous qualitative and quantitative analysis are required for the processes governing the toxicokinetics and dynamics of metals in aquatic organisms.     

The genotoxicity of priority polycyclic aromatic hydrocarbons in complex mixtures

Risk assessment of complex environmental samples suffers from difficulty in identifying toxic components, inadequacy of available toxicity data, and a paucity of knowledge about the behavior of geno(toxic) substances in complex mixtures. Lack of information about the behavior of toxic substances in complex mixtures is often avoided by assuming that the toxicity of a mixture is simply the sum of the expected effects from each mixture component, i.e. no synergistic or antagonistic interactions. Although this assumption is supported by research investigating non-genotoxic end-points, the literature describing the behavior of genotoxic substances in complex mixtures is sparse and, occasionally, contradictory. In this study, the results of polycyclic aromatic hydrocarbon (PAH) analyses on freshwater bivalves were used to prepare realistic mixtures containing up to 16 PAHs. The SOS genotoxicity of the mixtures and each component were then assessed in an effort to evaluate the additivity of PAH genotoxicity. At nominal PAH concentrations above 1 microg/ml, observed genotoxic responses were far lower than those predicted under the assumption of additivity. At nominal concentrations below 0.75 microg/ml, differences are smaller and occasionally negligible, indicating that the genotoxicity of unsubstituted homocyclic PAHs is additive or slightly less than additive. Other researchers who have investigated the mutagenicity, carcinogenicity, and DNA binding activity of mixtures containing unsubstituted homocyclic PAHs have also reported additive effects. Therefore, the mutagenic risk posed by simple, well-characterized mixtures of priority PAHs can reasonably be estimated as the sum of the risks posed by the mixture components. Current data indicate that less-than-additive effects likely result from saturation of metabolic pathways needed to activate mutagenic PAHs.     

Randomization Modelling of the Crossover Experiment for Clinical Trials

The two-period cross-over experiment for clinical trials has been examined by several writers following a Gaussian linear model approach. Some authors have expressed interest in the “derivation of the finite permutation model” and have pointed out that the randomization approach to modeling the two-period cross-over design “would highlight the importance of randomizing the subjects to the two groups as a basis for inference”. However, in the literature, there is no development of the randomization approach to this important design. In this paper, after a statement of the experimental design and formulation of the observation random variables of the finite population, two additive randomization models—one with residual effects, the other without—which are the analogues of Grizzle's Gaussian models, are derived. Statistical inference is developed for these randomization models and the results are compared with those of the corresponding Gaussian models. Also, exact inference based upon Fischer's approach is presented.     

On the Additive and Multiplicative Models of Relative Risk

Two popular models of absence of synergism in epidemiologic cohort studies are analyzed and compared. It is shown that the statistical concept of the union of independent events that traditionally has given rise to the “additive” model of relative risk can also generate the “multiplicative” model of relative risk. In fact, the same set of approximating conditions can be used to generate both models, which suggests a lack of identifiability under the traditional approach. An alternate approach is proposed in this paper. The new approach does not require the assumption that background risk factors are independent from causal agents of interest. The concept of “dose additivity” is discussed.     

GENETIC VARIATION AND COVARIATION FOR CHARACTERISTICS ASSOCIATED WITH CADMIUM TOLERANCE IN NATURAL POPULATIONS OF THE SPRINGTAIL ORCHESELLA CINCTA (L.)

Heavy metals can be strong and stable directional selective agents for metal-exposed populations. Genetic variation for the metal-tolerance characteristic “cadmium excretion efficiency” was studied in populations of the collembolan Orchesella cincta from a reference- and a metal-contaminated forest soil. Previously it has been shown that “excretion efficiency” influences tolerance through midgut-mediated immobilization and excretion of toxic metal ions, and that an increased mean excretion efficiency is present in animals inhabiting metal-contaminated litter. In the present research, offspring-parent regressions showed that additive genetic variation for cadmium excretion efficiency was present in the population from the reference site. The heritability estimate was 0.33. In the natural population exposed to heavy metals from an industrial source, additive genetic variation was not significantly different from zero. Differences in the heritability between the reference and the exposed population were not significant. Genetic variation for cadmium excretion efficiency allows for a response to selection in the reference population. Such a response has probably occurred in the metal-exposed population. Half-sib analysis with animals from the reference population was used to estimate genetic variation and maternal effects for excretion efficiency, relative growth rate and molting frequency, and to determine genetic correlations between these characteristics. Additive genetic variation was demonstrated for all three characteristics, heritability estimates were 0.48, 0.75 and 0.46, respectively. Maternal effects were low for excretion efficiency and molting frequency, but may be present for relative growth rate. Phenotypic and genetic correlations among these characteristics were positive. The environmental correlation between relative growth rate and molting frequency was positive, others were negative. Direct selection for any of the characteristics, or genetic correlations between tolerance characteristics and growth characteristics, or both may have caused the responses previously observed in field populations.     

Macrobenthic–mud relations strengthen the foundation for benthic index development: A case study from shallow,temperate New Zealand estuaries

Globally the input of sediment to coastal systems, in particular to estuaries, is predicted to increase due to anthropogenic activities. Sediment mud content is a powerful driver of ecologically important, macrobenthic taxa in estuarine intertidal flats. Accordingly, forecasting species responses to increased sedimentation is fundamental for effective ecosystem management, particularly for productive, geologically young, and sand-dominated estuaries that characterise many countries, including New Zealand (NZ). Modelling studies have highlighted the non-linear, highly variable responses of taxa to mud concentration. However, existing taxon-specific models have not adequately accounted for the full mud gradient, the influence of potentially confounding variables (e.g. organic enrichment, heavy metal concentrations), or regional differences in species responses. Furthermore, such models are often based on qualitative expert consensus of the membership of taxa in ecological groups that characterise their sensitivity to mud content. In this study, data from 25 unmodified to highly disturbed, shallow NZ estuaries, were used to develop an ecologically relevant model to relate the responses of 39 taxa to sediment mud content for use in the intertidal flats of shallow, temperate estuaries. Preliminary analyses indicated that sediment mud content was the dominant driver of macroinvertebrate community composition among sites, total organic carbon was of secondary importance and heavy metals did not explain significant variation in composition. Regression analysis revealed a significant linear relationship between sediment mud and total organic carbon content, which permitted subsequent analyses to be based on mud content alone. Generalised additive models were used to develop taxon-specific models that, according to k-fold cross validation, accurately predicted both probability of presence (up to 79% deviance explained) and maximum density (up to 96% deviance explained) along the sediment mud gradient (0.1–92.3%). Estimates of “optimal mud range” and “distribution mud range” were quantitatively-derived for each taxon and used to categorise taxa into one of five ecological groups (identical to those used in existing biotic indices), based on their individual sensitivities to increasing mud content. By removing expert consensus from the grouping process, the classification methods established herein provide strong support for the use of quantitative indices for the assessment and management of estuarine condition in response to increasing sediment mud content. The findings indicate that NZ estuarine sediments (2–25% mud) support a more diverse and abundant macroinvertebrate assemblage and exhibit low organic enrichment (<1% total organic carbon) compared to estuaries with >25% mud content.     

Coexperiencing Psychotherapy as a Psychotechnical System

The main challenge of contemporary psychology is to fill the increasing split between research psychology and psychological practice. A creative response to this challenge is found in a general methodological approach, which L.S. Vygotsky called the “philosophy of practice” or “psychotechnics.” This article describes a psychotechnical system called “coexperiencing psychotherapy.” This psychotechnical system combines science, practice, and education. From the perspective of general psychological theory the article describes a model of an “integral unit of psychological analysis,” in which the main general psychological categories (activity, set, relationship, and communication) are synthesized. In addition, the article presents a theoretical interpretation of experiencing (perezhivanie) as a productive meaning-generating activity. Finally, conceptual models of levels, registers, and structures of consciousness are proposed. From a psychotherapeutic practice perspective, a system of a “psychotechnical unit” of the psychotherapeutic process and structure of situation is given. The general method of coexperiencing psychotherapy is “understanding.” The educational dimension of the psychotechnical system remains outside the scope of the current article.     

A hierarchical Bayesian regression model that reduces uncertainty in material demand predictions

Predictions of metal consumption are vital for criticality assessments and sustainability analyses. Although demand for a material varies strongly by region and end-use sector, statistical models of demand typically predict demand using regression analyses at an aggregated global level (“fully pooled models”). “Un-pooled” regression models that predict demand at a disaggregated country or regional level face challenges due to limited data availability and large uncertainty. In this paper, we propose a Bayesian hierarchical model that can simultaneously identify heterogeneous demand parameters (like price and income elasticities) for individual regions and sectors, as well as global parameters. We demonstrate the model's value by estimating income and price elasticity of copper demand in five sectors (Transportation, Electrical, Construction, Manufacturing, and Other) and five regions (North America, Europe, Japan, China, and Rest of World). To validate the benefits of the Bayesian approach, we compare the model to both a “fully pooled” and an “un-pooled” model. The Bayesian model can predict global demand with similar uncertainty as a fully pooled regression model, while additionally capturing regional heterogeneity in income elasticity of demand. Compared to un-pooled models that predict demand for individual countries and sectors separately, our model reduces the uncertainty of parameter estimates by more than 50%. The hierarchical Bayesian modeling approach we propose can be used for various commodities, improving material demand projections used to study the impact of policies on mining sector emissions and informing investment in critical material production.     

Hazard and risk assessment of human exposure to toxic metals using in vitro digestion assay

Clean-up targets for toxic metals require that the site be “fit for purpose”. This means that targets are set with respect to defined receptors that reflect intended land-use. In this study, the likely threat of human exposure to toxic metals has been evaluated by simulating the human digestion process in vitro. The effects of key attributes (i.e. sample fraction size, pH, K_d and total metal concentrations) on the bioavailability of Cu and Ni were also investigated. Total metal concentration was the key explanatory factor for Cu and Ni bioavailability. A comparative ranking of metal concentrations in the context of tolerable daily intakes for Cu and Ni confirmed that the pH has the greatest impact on metals bioavailability. Rapid screening of key attributes and total toxic metal doses can reveal the relative hazard imposed on human, and this approach should be considered when defining threshold values for human protection.     

Analysis of contingency table data on torus mandibularis using a log linear model

The hypothesized sexual difference in the incidence of torus mandibularis in Eskimoid groups, as well as age and group differences, was studied in two Northwest Territories Eskimo groups and in an Aleut group (examined by Moorrees). The data were analyzed using statistical methods new to the field of anthropology. The method analyzes data sampled from a multinomial distribution. A hierarchy of log linear models are fitted to the cell counts of a contingency table. An iterative proportional fitting procedure is used to obtain expected cell counts under each log linear model. The “goodness of fit” of each model is tested by the log likelihood ratio. This statistic can be partitioned into additive components such that differences between models can be tested. In this way a “best” model, from the hierarchy of models, is chosen. Among these three groups of Eskimos, the incidence of torus mandibularis was not affected by sex but was affected by age and was different between the three groups.     

The manipulation mechanism of “push–pull” habitat management strategy and advances in its application

The “push–pull” habitat management strategy, as a new powerful and effective tool in integrated pest management (IPM), uses a combination of behavior-modifying stimuli to manipulate the distribution and abundance of pests and/or their natural enemies for pest control. In the “push–pull” strategy, pests are repelled or deterred away from the protected resource (push) by stimuli that disturb the host location and modulate the host become unattractive or unsuitable for the feeding and oviposition of pests. By using highly attractive stimuli, the target pests are simultaneously attracted (pull) to the specific source in which they are subsequently concentrated, facilitating their elimination and leaving the protected resource. Since stimuli usually are nontoxic, either “push” or “pull” components, the strategy is usually companied by population-reduced methods, such as using insecticides, exploiting nature enemies, and placing traps. Among them, methods of biological control are the most preferred. The “push–pull” strategies maximize efficacy of behavior-modifying stimuli through the additive and synergistic effects of integrating the use of methods for population reduction. In this review, the principles of the “push–pull” strategy were firstly described, then the potential behavior-modifying stimuli for “push” and “pull” components were introduced. The stimuli for use in “push–pull” strategies primarily include visual cues and chemical cues (synthetic or plant- or insect-derived semiochemicals). Visual stimuli, repellent and trap plants, host and non-host volatiles, insect pheromones, and antifeedants and oviposition deterrents are usually applied as the potential stimuli in the “push–pull” strategy for pest control. The stimuli are grouped as long-range stimuli and short-range stimuli. In addition, we also summarize models of “push–pull” habitat management strategy, such as agriculture, horticulture and forestry, of pest control and some successful case studies in applying of “push–pull” strategy and its potential ecological benefits. The “push–pull” technology (PPT), so far the most effective “push–pull” strategy in practice by farmers, developed for management of both stemborers and Striga hermonthica in maize-based farming system in eastern Africa were reviewed. The PPT uses an intercrop of repellent plants and border crops of attractive trap plants. Stemborer moths are effectively repelled away from the maize crop (push) by Desmodium and molasses grass, and are subsequently attracted (or trapped) to (pull) by the Napier grass and Sudan grass which emit the green leaf volatiles (GLVs) showing attractant properties. Finally, the problems in current research and future perspectives of the “push–pull” habitat management strategy are discussed in the present paper.     

Metabarcoding of freshwater invertebrates to detect the effects of a pesticide spill

Biomonitoring underpins the environmental assessment of freshwater ecosystems and guides management and conservation. Current methodology for surveys of (macro)invertebrates uses coarse taxonomic identification where species‐level resolution is difficult to obtain. Next‐generation sequencing of entire assemblages (metabarcoding) provides a new approach for species detection, but requires further validation. We used metabarcoding of invertebrate assemblages with two fragments of the cox1 “barcode” and partial nuclear ribosomal (SSU) genes, to assess the effects of a pesticide spill in the River Kennet (southern England). Operational taxonomic unit (OTU) recovery was tested under 72 parameters (read denoising, filtering, pair merging and clustering). Similar taxonomic profiles were obtained under a broad range of parameters. The SSU marker recovered Platyhelminthes and Nematoda, missed by cox1, while Rotifera were only amplified with cox1. A reference set was created from all available barcode entries for Arthropoda in the BOLD database and clustered into OTUs. The River Kennet metabarcoding produced matches to 207 of these reference OTUs, five times the number of species recognized with morphological monitoring. The increase was due to the following: greater taxonomic resolution (e.g., splitting a single morphotaxon “Chironomidae” into 55 named OTUs); splitting of Linnaean binomials into multiple molecular OTUs; and the use of a filtration‐flotation protocol for extraction of minute specimens (meiofauna). Community analyses revealed strong differences between “impacted” vs. “control” samples, detectable with each gene marker, for each major taxonomic group, and for meio‐ and macrofaunal samples separately. Thus, highly resolved taxonomic data can be extracted at a fraction of the time and cost of traditional nonmolecular methods, opening new avenues for freshwater invertebrate biodiversity monitoring and molecular ecology.     

What is hierarchical selection?

It has been proposed that natural selection occurs on a hierarchy of levels, of which the organismic level is neither the top nor the bottom. This hypothesis leads to the following practical problem: in general, how does one tell if a given phenomenon is a result of selection on level X or level Y. How does one tell what the units of selection actually are? It is convenient to assume that a unit of selection may be defined as a type of entity for which there exists, among all entities on the same “level” as that entity, an additive component of variance for some specific component F of fitness which does not appear as an additive component of variance in any decomposition of this F among entities at any lower level. But such a definition implicitly assumes that if f(x, y) depends nonadditively on its arguments, there must be interaction between the quantities which x and y represent. This assumption is incorrect. And one cannot avoid this error by speaking of “transformability to additivity” instead of merely “additivity”. A general mathematical formulation of the concepts of interaction and non-interaction is proposed, followed by a correspondingly modified approach to the definition of a unit of selection. The practical difficulty of verifying the presence of hierarchical selection is discussed.     

Two-enzyme active transport in vitro with ph induced asymmetrical functional structures.: III. Discussions based on numerical treatments of the time-dependent evolutions

Three complementary models have been considered in which pH gradients (step function. linear pH or linear H^?) impose asymmetry on a two-enzyme mixture. If the “combined pH dependences” of enzymes is pro-asymmetrical, the pH gradient induces an asymmetrical distribution of potential activities (“latent” asymmetry of functional structure). When substrate is added, “developed” asymmetry of effective activities appears which results in “substrate space wave” and pumping when the catalysed reaction couple is “inversible”. It is shown that only one steady state exists for a given boundary condition and is attained when the “combined effective activity” of enzymes is nil: the stationary flux with symmetrical boundaries or the stationary load with moving boundaries is proportional to “effective global activities” of enzymes. “Equivalent square models” could be proposed that would be able to describe “functional” or “permanent” structure pumps as well. These models belong to the thermodynamic branch and the asymmetrical “space wave” substrate concentration profiles obtained must be distinguished from dissipative structures. It appears that such primary active transport pumps are chemical equivalents of heat pumps.     

Quantifying the causal pathways contributing to natural selection

The consequences of natural selection can be understood from a purely statistical perspective. In contrast, an explicitly causal approach is required to understand why trait values covary with fitness. In particular, key evolutionary constructs, such as sexual selection, fecundity selection, and so on, are best understood as selection via particular fitness components. To formalize and operationalize these concepts, we must disentangle the various causal pathways contributing to selection. Such decompositions are currently only known for linear models, where they are sometimes referred to as “Wright's rules.” Here, we provide a general framework, based on path analysis, for partitioning selection among its contributing causal pathways. We show how the extended selection gradient—which represents selection arising from a trait's causal effects on fitness—can be decomposed into path-specific selection gradients, which correspond to distinct causal mechanisms of selection. This framework allows for nonlinear effects and nonadditive interactions among variables, which may be estimated using standard statistical methods (e.g., generalized linear [mixed] models or generalized additive models). We thus provide a generalization of Wright's path rules that accommodates the nonlinear and nonadditive mechanisms by which natural selection commonly arises.     

Adaptive Long-Term Monitoring of Soil Health in Metal Phytostabilization: Ecological Attributes and Ecosystem Services Based on Soil Microbial Parametersxs

Phytostabilization is a promising option for the remediation of metal contaminated soils which requires the implementation of long-term monitoring programs. We here propose to incorporate the paradigm of “adaptive monitoring”, which enables monitoring programs to evolve iteratively as new information emerges and research questions change, to metal phytostabilization. Posing good questions that cover the chemical, toxicological and ecological concerns associated to metal contaminated soils is critical for an efficient long-term phytostabilization monitoring program. Regarding the ecological concerns, soil microbial parameters are most valuable indicators of the effectiveness of metal phytostabilization processes in terms of recovery of soil health. We suggest to group soil microbial parameters in higher-level categories such as “ecological attributes” (vigor, organization, stability) or “ecosystem services” in order to facilitate interpretation and, most importantly, to provide long-term phytostabilization monitoring programs with the required stability through time against changes in techniques, methods, interests, etc. that will inevitably occur during the monitoring program. Finally, a Phytostabilization Monitoring Card, based on both ecological attributes and ecosystem services, for soil microbial properties is provided.     

MDMPR:小鼠发育代谢表型库

小鼠发育代谢表型库(Mouse Developmental and Metabolic Phenotype Repository,MDMPR)是一个致力于小鼠资源和表型数据实时共享的开放性平台,它依托于科技部重点研发计划“发育编程及其代谢调节”专项项目“建立小鼠发育代谢表型库”。该项目预计在5年内完成500个发育代谢相关小鼠敲除模型的建立,并对其表型数据进行标准化的解析、建立表型数据库。MDMPR作为一个资源及数据集成的库,由多个子系统作为支撑,包括ES细胞数据库、项目管理系统、繁育管理系统、精子库管理系统、表型分析系统,信息化管理深入到项目中每个环节,从基因突变ES细胞制备、基因突变小鼠制备、小鼠繁育,精子冻存到最终的表型分析、数据处理及展示,保证了MDMPR产生数据的真实性及实时性。MDMPR除了不断地推进项目进行,增加自身产生的数据外,也在积极的整合其他的资源及数据,如人特异性基因敲除ES细胞库、蛋白相互作用数据库(STRING)、核心转录调节环路(dbCoRc)和Enhancer-Indel数据库,今后还将进一步整合,帮助发育代谢及其他领域的研究人员能够一站式的获取所需资源和数据、加快研究进程,最终服务于全人类的医疗事业。     

Arsenic and Manganese Alter Lead Deposition in the Rat

Lead (Pb) continues to be a major toxic metal in the environment. Pb exposure frequently occurs in the presence of other metals, such as arsenic (As) and manganese (Mn). Continued exposure to low levels of these metals may lead to long-term toxic effects due to their accumulation in several organs. Despite the recognition that metals in a mixture may alter each other’s toxicity by affecting deposition, there is dearth of information on their interactions in vivo. In this work, we investigated the effect of As and Mn on Pb tissue deposition, focusing on the kidney, brain, and liver. Wistar rats were treated with eight doses of each single metal, Pb (5 mg/Kg bw), As (60 mg/L), and Mn 10 mg/Kg bw), or the same doses in a triple metal mixture. The kidney, brain, liver, blood, and urine Pb, As, and Mn concentrations were determined by graphite furnace atomic absorption spectrophotometry. The Pb kidney, brain, and liver concentrations in the metal-mixture-treated group were significantly increased compared to the Pb-alone-treated group, being more pronounced in the kidney (5.4-fold), brain (2.5-fold), and liver (1.6-fold). Urinary excretion of Pb in the metal-mixture-treated rats significantly increased compared with the Pb-treated group, although blood Pb concentrations were analogous to the Pb-treated group. Co-treatment with As, Mn, and Pb alters Pb deposition compared to Pb alone treatment, increasing Pb accumulation predominantly in the kidney and brain. Blood Pb levels, unlike urine, do not reflect the increased Pb deposition in the kidney and brain. Taken together, the results suggest that the nephro- and neurotoxicity of “real-life” Pb exposure scenarios should be considered within the context of metal mixture exposures.     

Database searching and accounting of multiplexed precursor and product ion spectra from the data independent analysis of simple and complex peptide mixtures

A novel database search algorithm is presented for the qualitative identification of proteins over a wide dynamic range, both in simple and complex biological samples. The algorithm has been designed for the analysis of data originating from data independent acquisitions, whereby multiple precursor ions are fragmented simultaneously. Measurements used by the algorithm include retention time, ion intensities, charge state, and accurate masses on both precursor and product ions from LC‐MS data. The search algorithm uses an iterative process whereby each iteration incrementally increases the selectivity, specificity, and sensitivity of the overall strategy. Increased specificity is obtained by utilizing a subset database search approach, whereby for each subsequent stage of the search, only those peptides from securely identified proteins are queried. Tentative peptide and protein identifications are ranked and scored by their relative correlation to a number of models of known and empirically derived physicochemical attributes of proteins and peptides. In addition, the algorithm utilizes decoy database techniques for automatically determining the false positive identification rates. The search algorithm has been tested by comparing the search results from a four‐protein mixture, the same four‐protein mixture spiked into a complex biological background, and a variety of other “system” type protein digest mixtures. The method was validated independently by data dependent methods, while concurrently relying on replication and selectivity. Comparisons were also performed with other commercially and publicly available peptide fragmentation search algorithms. The presented results demonstrate the ability to correctly identify peptides and proteins from data independent acquisition strategies with high sensitivity and specificity. They also illustrate a more comprehensive analysis of the samples studied; providing approximately 20% more protein identifications, compared to a more conventional data directed approach using the same identification criteria, with a concurrent increase in both sequence coverage and the number of modified peptides.