Feeding and nutritional considerations in aquatic toxicology

The nutritional status of an aquatic organism, both prior to and during testing, can significantly modify the apparent toxicity of a chemical. In order to decrease the variability of toxicity test results, both within and between laboratories, feeding regimes, feed types and proximate composition of diets should be routinely reported. The advantages and metabolic effects of various feeding practices currently used in toxicity testing (fasting, starvation, feeding as a percentage of body weight, feeding ad libitum and pair feeding) are discussed. The disadvantages of monitoring nutritional status of test organisms are also reviewed and suggestions are offered as to how best to monitor nutritional status.     

Use of environmental challenges in behavioral toxicology

The term environmental challenges encompasses variables that are either known or suspected to affect a baseline of behavior. Environmental challenges can be used to provide information that is important for characterizing the behavioral effects of prior exposure to a toxicant, as well as for revealing effects of the toxicant that may not otherwise be apparent in the baseline under investigation. The use of environmental challenges can be applied in studies of all known classes of behavior, and in each case is limited only to the extent that appropriate variables can be identified and manipulated. Use of environmental challenges may be particularly relevant for studies of schedule-controlled operant behavior because many of the controlling variables have already been well specified. The rationale for using environmental challenges to characterize the behavioral effects of toxicants is very similar to that for using pharmacological challenges; both represent promising new research strategies in behavioral toxicology.     

MicroRNA在环境毒理学中的研究进展

MicroRNA（miRNA）是一类长为20～24nt的非编码单链小分子RNA,主要存在于真核生物中,具有组织特异性、无开放阅读框等特点,在转录或翻译水平调控基因表达,参与细胞增殖、分化、凋亡,并与炎症、肿瘤等疾病发生、发展密切相关。环境毒理学研究表明,当生物暴露于环境化学物质时,会引起相关miRNA表达发生变化,进而导致其靶基因表达发生改变。因此,有必要明确环境化学物质、miRNA和相关靶基因三者问的作用关系。在环境毒理学研究和环境监测中,miRNA可作为识别环境中化学物质基因毒性和致癌性的生物标记物,并可用于预测环境化学物质对生物体的毒性。     

Trangenic fish as models in environmental toxicology

Historically, fish have played significant roles in assessing potential risks associated with exposure to chemical contamination in aquatic environments. Considering the contributions of transgenic rodent models to biomedicine, it is reasoned that the development of transgenic fish could enhance the role of fish in environmental toxicology. Application of transgenic fish in environmental studies remains at an early stage, but recent introduction of new models and methods demonstrates progress. Rapid advances are most evident in the area of in vivo mutagenesis using fish carrying transgenes that serve as recoverable mutational targets. These models highlight many advantages afforded by fish as models and illustrate important issues that apply broadly to transgenic fish in environmental toxicology. Development of fish models carrying identical transgenes to those found in rodents is beneficial and has revealed that numerous aspects of in vivo mutagenesis are similar between the two classes of vertebrates. Researchers have revealed that fish exhibit frequencies of spontaneous mutations similar to rodents and respond to mutagen exposure consistent with known mutagenic mechanisms. Results have demonstrated the feasibility of in vivo mutation analyses using transgenic fish and have illustrated their potential value as a comparative animal model. Challenges to development and application of transgenic fish relate to the needs for improved efficiencies in transgenic technology and in aspects of fish husbandry and use. By taking advantage of the valuable and unique attributes of fish as test organisms, it is anticipated that transgenic fish will make significant contributions to studies of environmentally induced diseases.     

Emerging issues in traditional Chinese medicine

Traditional Chinese medicine (TCM) has many beneficial effects and has been practiced for several thousand years. It is known to treat the cause of a disease rather than to alleviate its symptoms. Based on a belief that TCM is natural, safe, and of lower cost, consumers worldwide are spending more out-of-pocket money on this form of therapy. This increased spending, and reports of adverse reactions, has drawn the attention of many regulatory agencies. Scientists have called for more evidence-based and scientific research on the risks and benefits of TCM. In Canada, the Natural Health Product Regulations came into effect January 2004. TCM herbal product manufacturers will need to provide products of reputable quality to the market. Many will apply modern technology and good science to support their products. The issues facing producers, scientists, and consumers alike are quality control and assessment, standardization of bioactive components, mechanisms of actions, and integration of the evolved modern Chinese medicine into the healthcare system. Solid science, better regulation of the final product, and better education of consumers are necessary to extract the best of TCM to complement existing conventional medicine to deliver the best healthcare.     

Chromium: a review of environmental and occupational toxicology

The following topics are covered in this brief review on the environmental and occupational toxicology of chromium: occurrence, production and uses of chromium and chromium compounds; experimental toxicology; chromium toxicity for man; hygienic and ecologic aspects of chromium contamination of the environment. The review provides a conclusive evidence which suggests that chromium, especially its hexavalent form, is both toxic and carcinogenic, but its trivalent form is physiologically essential in the metabolism of insulin. It is also emphasized that among the major sources of environmental chromium today are the cement industry and the increasingly widespread use of chromium compounds added as an anticorrosion admixture to a variety of cooling systems, e.g. in large power plants, which may greatly contribute to the overall pollution of outdoor air at the sites.     

Nickel: a review of its occupational and environmental toxicology

Nickel and nickel compounds belong to the classic noxious agents encountered in industry, but is also known to affect non-occupationally exposed individuals, especially those handling stainless-steel and nickel plated articles of everyday use. For plants and some vertebrates, specifically for mammals, nickel is indispensable as one of the essential trace elements. The most important health problems due to exposure to nickel and nickel compounds are allergic dermatitis (nickel itch) and increased incidence of cancers of the lungs and nasal mucosa encountered among the workers after a long-term over-exposure to nickel. In this respect the most hazardous nickel compounds appear to be nickel sulfide and nickel oxide. The monitoring of nickel exposure levels can be based on blood serum and urine analyses, but also on nickel determinations in hair which have proved promising even in groups of non-occupationally exposed individuals. Nickel carbonyl is the most toxic of all of the nickel compounds encountered, but because of its relatively short half-life it does not seem to represent any actual biohazard from the standpoint of environmental pollution. To prevent incidence of malignancies it is recommended to include in the routine plan of the preventive medical examinations also the cytologic analysis supplemented, in the case of cytologic positivity, with the bioptic examination for epithelial dysplasia. A systematic medical surveillance of workers with known long-term exposure to nickel is, of course, essential. At present, a major attention is centered on biochemical interactions of nickel with copper, cadmium, iron, iodine and particularly with manganese known to significantly reduce the experimental carcinogenicity of nickel and nickel compounds.     

Emerging issues of connexin channels: biophysics fills the gap

This summary is a proposed synthesis of available information for the non-specialist. It does not incorporate all the published data, is inconsistent with some, and reflects the biases of the author. Connexin proteins have a common transmembrane topology, with four alpha-helical transmembrane domains, two extracellular loops, a cytoplasmic loop, and cytoplasmic N- and C-terminal domains. The sequences are most conserved in the transmembrane and extracellular domains, yet many of the key functional differences between connexins are determined by amino-acid differences in these largely conserved domains. Each extracellular loop contains three cysteines with invariant spacing (save one isoform) that are required for channel function. The junctional channel is composed of two end-to-end hemichannels, each of which is a hexamer of connexin subunits. Hemichannels formed by some connexin isoforms can function as well-behaved, single-membrane-spanning channels in plasma membrane. In junctional channels, the cysteines in the extracellular loops form intra-monomer disulfide bonds between the two loops, not intermonomer or inter-hemichannel bonds. The end-to-end homophilic binding between hemichannels is via non-covalent interactions. Mutagenesis studies suggest that the docking region contains beta structures, and may resemble to some degree the beta-barrel structure of porin channels. The two hemichannels that compose a junctional channel are rotationally staggered by approximately 30 degrees relative to each other so that the alpha-helices of each connexin monomer are axially aligned with the alpha-helices of two adjacent monomers in the apposed hemichannel. At present there is a published 3D map with 7.5 A resolution in the plane of the membrane, based on electron cryomicroscopy of 2D crystals of junctional channels formed by C-terminal truncated Cx43. The correspondence between the imaged transmembrane alpha-helices and the known transmembrane amino-acid sequences is a matter of debate. Each of the approximately 20 connexin isoforms produces channels with distinct unitary conductances, molecular permeabilities, and electrical and chemical gating sensitivities. The channels can be heteromeric, and subfamilies among connexins largely determine heteromeric specificity, similar to the specificities within the voltage-dependent potassium channel superfamily. The second extracellular loop contains the primary determinants of the specificity of hemichannel-hemichannel docking (analogous to the tetramerization domain of potassium channels). The 7.5 A map shows that each monomer exposes only two transmembrane alpha-helices to the pore lumen. However the conductance state of the imaged structure and the effects of the C-terminal truncation are unknown, so it is possible that other transmembrane domains contribute to the lumen in other functional states of the channel. In the transmembrane region, SCAM and mutagenesis data suggest that parts of the first three transmembrane alpha-helices are exposed to the lumen. Some of these data are contradictory, but may reflect conformational or isoform differences. There is reason to think that the first part of the N-terminal cytoplasmic domain can line the pore in some conformations. In the extracellular part of junctional channels, the N-terminal portion of the first extracellular loop is exposed to the lumen. The unitary conductances through connexin channels vary over an order of magnitude, from 15 pS to over 300 pS. There is a range of charge selectivities among atomic ions, from slightly anion selective to highly cation selective, which does not correlate with unitary conductance. There appear to be substantial ion-ion interactions within the pore, making the GHK model of assessing selectivities of limited value. Pores formed by different connexins have a range of limiting diameters as assessed by uncharged and charged probes, which also does not correlate with unitary conductance (i.e. some have high conductance but have a narrow limiting diameter, and vice versa). Channels formed by different connexins have different permeabilities to various cytoplasmic molecules. Where it has been assessed, the selectivity among cytoplasmic molecules is substantial and does not correlate in an obvious manner with the size selectivity data derived from fluorescent tracer studies, suggesting there are chemical specificities within the pore that enhance or reduce permeability to specific cytoplasmic molecules, functionally analogous to the ability of some porins to facilitate transport of specific substrates. For example, heteromeric channels with different stoichiometries or arrangements of isoforms can distinguish among second messengers. The differences in permeability to cytoplasmic molecules have biological consequences; in most cases one connexin cannot fully substitute for another. Voltage and chemical gating mechanisms largely operate within each hemichannel, though there is evidence for inter-hemichannel allosteric effects as well. There are at least two distinct gating mechanisms. One (Vj-gating) is a voltage-driven mechanism that governs rapid transitions between conducting states. Its voltage sensor involves charges in the first several positions of the cytoplasmic N-terminal domain and possibly in the N-terminal part of the first extracellular loop, which may both be exposed to the lumen of the pore in some states. The polarity of Vj-gating sensitivity is connexin-specific, closing with depolarization for some connexins and with hyperpolarization for others. The polarity can be reversed by point mutations at the second position. The lower conductance states induced by Vj-gating correspond to physical restrictions of the pore, and thus restricted or eliminated molecular permeation. Since the channels are not fully closed by Vj-gating, it can be seen as a way to eliminate molecular signaling while leaving electrical signaling operational. A second, independent gating mechanism mediates slow transitions (approximately 10-30 ms) into and out of non-conducting state(s). These transitions can occur in response to voltage ('loop gating'), chemical factors such as pH and lipophiles ('chemical gating'), and the docking of two hemichannels (sometimes called the 'docking gate'). These slow transitions may reflect a common structural change induced by these several effectors (electrical, chemical and homodimerization). Alternatively, they could reflect distinct gating processes responding to one or more of these effectors, that are indistinguishable at the single-channel level and have yet to be resolved mechanistically. The slow or loop gate closes with hyperpolarization. As a result, where Vj-gating closes with depolarization, individual hemichannels can close in response to both polarities of voltage (but only to a subconductance state for the Vj-gating polarity). Because of this, it is difficult to assign a macroscopic voltage sensitivity, or its modification due to mutagenesis, chemical modification or heteromeric interactions, to one or the other of these very distinct voltage-sensitive processes. This distinction can be made reliably only at the single-channel level. The Vj-gating voltage sensor and the loop-gating voltage sensor appear to be independent structures, since the Vj-gating voltage sensitivity can modified without effect on loop gating. For some connexins, certain modifications of the C-terminal domain seem to interfere with the operation of the Vj-gate while leaving loop gating unaffected. In some connexins, but not all, the chemical sensitivity to pH can involve interactions between regions of the C-terminal domain and cytoplasmic loop. Whether these regions exert their effects directly by physically blocking the pore, or by allosteric mechanisms (which may be more consistent with the relatively long time-course of closure) is not clear. For several connexins, truncation of the C-terminal domain eliminates the pH sensitivity, and co-expressing the domain with the truncated connexin restores the pH sensitivity. This has a functional resemblance to the particle-receptor mechanism for N-type inactivation of Shaker channels. What is being protonated is not clear, and may involve cytoplasmic factors, such as endogenous aminosulfonates. For other connexins, the action of pH does not involve the C-terminal domain and seems due to direct protonation of connexin. PKC phosphorylation of serine(s) in the C-terminal domain can affect the substate occupancy of at least one connexin. Phosphorylation of series in the C-terminal domain by MAP kinase appears to facilitate an interaction between it and an unknown receptor domain to eliminate coupling. This process has yet to be studied at the single-channel level. It also has a functional analogy to the particle-receptor model of channel inactivation. Both MAP kinase phosphorylation-induced and pH-induced inhibition can be mediated in truncated connexins by the corresponding free peptide. However, the relation between these two mechanisms are unexplored, as are specific mechanisms of direct endogenous regulation of connexin channel activity. (ABSTRACT TRUNCATED)     

Emerging foundations: nano-engineering and bio-microelectronics for environmental biotechnology

The growth of nanotechnology, the emergence of 'nanobiotechnology', and the incorporation of living organisms in biomicroelectronic devices are revolutionizing the interdisciplinary opportunities for microbiologists to participate in understanding, developing and exploiting microbial processes in and from the environment.     

Towards computational models of cells for environmental toxicology

This paper outlines an approach to the development of computational models of cells for marine environmental toxicology. Exposure of cells to pollutants can lead to lysosomal damage and dysfunction, augmented autophagy, cellular dysfunction and atrophy and ultimately tissue pathology and organ damage. The application of carbon and nitrogen based models of intra cellular vesicular traffic for simulating the autophagic and lysosomal response of the hepatopancreatic digestive cells of marine molluscs is described. Two numerical models of the vesicular transport of carbon and nitrogen in the cell are presented. These demonstrate the importance of endocytotic uptake as a driver of lysosomal dynamics and the need to recognize and model it as a discrete process. Conceptual and mathematical models of the toxic impact of polycyclic aromatic hydrocarbons on the digestive gland are presented. The role of experimental research and the need to integrate it with modelling is highlighted.     

Optimal experimental design for a nonlinear response in environmental toxicology

A start-stop experiment in environmental toxicology provides a backdrop for this design discussion. The basic problem is to decide when to sample a nonlinear response in order to minimize the generalized variance of the estimated parameters. An easily coded heuristic optimization strategy can be applied to this problem to obtain optimal or nearly optimal designs. The efficiency of the heuristic approach allows a straightforward exploration of the sensitivity of the suggested design with respect to such problem-specific concerns as variance heterogeneity, time-grid resolution, design criteria, and interval specification of planning values for parameters. A second illustration of design optimization is briefly presented in the context of concentration spacing for a reproductive toxicity study.     

Emerging issues in the evolution of animal nuptial gifts

Uniquely positioned at the intersection of sexual selection, nutritional ecology and life-history theory, nuptial gifts are widespread and diverse. Despite extensive empirical study, we still have only a rudimentary understanding of gift evolution because we lack a unified conceptual framework for considering these traits. In this opinion piece, we tackle several issues that we believe have substantively hindered progress in this area. Here, we: (i) present a comprehensive definition and classification scheme for nuptial gifts (including those transferred by simultaneous hermaphrodites), (ii) outline evolutionary predictions for different gift types, and (iii) highlight some research directions to help facilitate progress in this field.     

Microbiological and environmental issues in show caves

Cultural tourism expanded in the last half of the twentieth century, and the interest of visitors has come to include caves containing archaeological remains. Some show caves attracted mass tourism, and economical interests prevailed over conservation, which led to a deterioration of the subterranean environment and the rock art. The presence and the role of microorganisms in caves is a topic that is often ignored in cave management. Knowledge of the colonisation patterns, the dispersion mechanisms, and the effect on human health and, when present, over rock art paintings of these microorganisms is of the utmost importance. In this review the most recent advances in the study of microorganisms in caves are presented, together with the environmental implications of the findings.     

淡水螯虾生理生态学与环境毒理学研究进展

综述了我国2种主养的淡水螯虾(克氏原螯虾和红螯螯虾)在生理生态学与环境毒理学方面的研究进展。总结了淡水螯虾的环境条件(盐度、温度和pH)适应范围、毒性污染物(氨氮、亚硝酸盐、重金属和农药等)的半致死浓度和安全浓度,以及环境胁迫和毒性污染物暴露对淡水螯虾生长、组织结构、生理代谢和免疫功能等的影响,为淡水螯虾养殖的水环境监测与调控提供参考依据。