Bioaccumulation processes in ecosystems

The fate of environmental pollutants — the various isotopes of elements, and inorganic or organic compounds — is a fundamental aspect of ecology and ecotoxicology, and bioaccumulation is a phenomenon often discussed in this context. Human activities have drastically altered natural concentrations of many substances in the environment and added numerous new chemicals. An understanding of the processes of bioaccumulation is important for several reasons. 1) Bioaccumulation in organisms may enhance the persistence of industrial chemicals in the ecosystem as a whole, since they can be fixed in the tissues of organisms. 2) Stored chemicals are not exposed to direct physical, chemical, or biochemical degradation. 3) Stored chemicals can directly affect an individual's health. 4) Predators of those organisms that have bioaccumulated harmful substances may be endangered by food chain effects. While former theories on the processes of bioaccumulation focused on single aspects that affect the extent of accumulation (such as the trophic level within the food chain or the lipophilicity of the chemical), modern theories are based on compartmental kinetics and the integration of various environmental interactions. Concepts include results from quantitative structure-activity relationships (QSAR), pharmacokinetics, ecophysiology and general biology, molecular genetic aspects and selection, and finally the structure of communities and man-made alterations in them.     

A structural view of nuclear hormone receptor: endocrine disruptor interactions

Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system by interfering with hormone biosynthesis, metabolism, or action. The molecular mechanisms of EDCs involve different pathways including interactions with nuclear hormone receptors (NHRs) which are primary targets of a large variety of environmental contaminants. Here, based on the crystal structures currently available in the Protein Data Bank, we review recent studies showing the many ways in which EDCs interact with NHRs and impact their signaling pathways. Like the estrogenic chemical diethylstilbestrol, some EDCs mimic the natural hormones through conserved protein–ligand contacts, while others, such as organotins, employ radically different binding mechanisms. Such structure-based knowledge, in addition to providing a better understanding of EDC activities, can be used to predict the endocrine-disrupting potential of environmental pollutants and may have applications in drug discovery.     

Heavy metal accumulation by bacteria and other microorganisms

Summary Bacteria, and other microorganisms, exhibit a number of metabolism-dependent and-independent processes or the uptake and accumulation of heavy metals and radionuclides. The removal of such harmful substances from effluents and waste waters by microbe-based technologies may provide an alternative or additional means of metal/radionuclide recovery for economic reasons and/or environmental protection. Both living and dead cells as well as products derived from or produced by microorganisms can be effective metal accumulators and there is evidence that some biomass-based clean-up processes are economically viable. However, many aspects of metal-microbe interactions remain unexploited in biotechnology and further development and application is necessary, particularly to the problem of radionuclide release into the environment.     

Implications of toxins in the ecology and evolution of plant pathogenic microorganisms: Bacteria

This review attempts to rationalise what is known about bacterial phytotoxins and associate it with the ecology and possible evolution of the producing organisms. Study of non-toxin producing variants gives insight into the ecological role of the toxin. Elucidation of chemical structures of phytotoxins has shown that many exist as families of analogous compounds. Studies on the variation of chemical structures and how they are distributed across species and genera can lead to development of hypotheses on evolutionary relationships. Knowledge on biosynthetic pathways to tosins allows recognition of specific enzymatic steps involved in developing the characteristic features of the structures. Phytotoxins often have a potent biochemical activity, and in some cases the producing organism has associated mechanisms to prevent action of the toxin upon itself; in such cases toxigenesis is clearly not a chance event. The various aspects of bacterial toxigenesis indicate that bacterial phytotoxins are special secondary metabolic products that play beneficial roles to the producing organisms in their various ecological niches.     

Correlation between car ownership and leukaemia: is non-occupational exposure to benzene from petrol and motor vehicle exhaust a causative factor in leukaemia and lymphoma?

Although there is widespread agreement that many cancers have environmental causes we are often unable to see associations between specific cancers and exposure to environmental chemicals. One might also speculate that the more widespread, common-place and 'normal' a chemical exposure is perceived to be then the less likely it will be that the exposure is recognised, let alone be considered to cause cancer. Widespread contamination of air by chemicals associated with internal combustion may be an example of one such 'invisible' carcinogenic exposure. Yet evidence is available which suggests that many leukaemia and lymphoma cases, as well as other cancers, may be caused by this mundane and ubiquitous environmental contamination. The hypothesis is developed that leukaemia 'clustering' as well as national leukaemia incidence may be related to non-occupational exposure to benzene formed by petrol combustion and resulting from petrol evaporation. The possible association between exposure to fuel vapours, internal combustion products and cancer merits much closer examination than it receives at present.     

Chemical ecology of oviposition in phytophagous insects

Summary Selection of a suitable site for oviposition by phytophagous insects is critical for successful development of the offspring. The behavioral events leading to oviposition are mediated to a large extent by chemical cues associated with potential host plants. Orientation and landing are primarily guided by volatile constituents of a plant, whereas assessment of a leaf surface depends on contact stimuli. Chemical mechanisms that ensure adequate spacing of progeny on limited resources include the production of oviposition-deterring pheromones as well as recognition of plant constituents released as a result of previous damage. Perception of chemical cues that affects oviposition involves receptors on antennae, tarsi, mouthparts or the ovipositor. Complex behavior such as tarsal drumming or stem runs may serve to provide increased receptor contact with chemical stimuli. Abiotic and biotic environmental factors often influence the production or release of behavior-modifying chemicals by a plant, and therefore affect oviposition preferences. Plant chemistry may be involved in associative learning, but may also lead to mistakes. Thus a clear correlation between oviposition preference and offspring success does not always exist.     

Les propriétés mécaniques du caoutchouc

Summary A survey of recent work on the theories of the peculiar mechanical behaviour of substances with rubber-like properties is given. All the theories are based on the assumption that these substances (including rubber itself) are composed of very long, flexible chainmolecules. Any segment of a chain is linked to two neighbouring segments by bonds similar to those which are present in typical solids and to all other neighbours by linkages like the bonds prevailing between the particles of liquids. The chain molecules are intermingled so as to form a kind of a felt.This state of aggregation is intermediate between the solid and the liquid; it is called the rubber-like state (état gommoïdal). Elasticity, viscosity and plastic flow as well as the influence of crystallization, vulcanization and degradation are discussed in terms of this theory.     

Chemical properties of alcohols and their protein binding sites

Alcohols affect a wide array of biological processes including protein folding, neurotransmission and immune responses. It is becoming clear that many of these effects are mediated by direct binding to proteins such as neurotransmitter receptors and signaling molecules. This review summarizes the unique chemical properties of alcohols which contribute to their biological effects. It is concluded that alcohols act mainly as hydrogen bond donors whose binding to the polypeptide chain is stabilized by hydrophobic interactions. The electronegativity of the O atom may also play a role in stabilizing contacts with the protein. Properties of alcohol binding sites have been derived from X-ray crystal structures of alcohol-protein complexes and from mutagenesis studies of ion channels and enzymes that bind alcohols. Common amino acid sequences and structural features are shared among the protein segments that are involved in alcohol binding. The alcohol binding site is thought to consist of a hydrogen bond acceptor in a turn or loop region that is often situated at the N-terminal end of an alpha-helix. The methylene chain of the alcohol molecule appears to be accommodated by a hydrophobic groove formed by two or more structural elements, frequently a turn and an alpha-helix. Binding at these sites may alter the local protein structure or displace bound solvent molecules and perturb the function of key proteins.     

Melatonin: presence and formation in invertebrates

In vertebrates, it is now clearly demonstrated that the pineal gland is implicated in conveying photoperiodic information via the daily pattern of melatonin secretion. Invertebrates, like vertebrates, use photoperiodic changes as a temporal cue to initiate physiological processes such as reproduction or diapause. How this information is integrated in invertebrates remains an unsolved question. Our review will be an attempt to evaluate the possible role of melatonin in conveying photoperiodic information in invertebrates. It is now well demonstrated in both vertebrates and invertebrates that melatonin as well as its precursors or synthesizing enzymes are present in various organs implicated in photoreceptive processes or in circadian pacemaking. Melatonin, serotonin or N-acetyltransferase have been found in the head, the eyes, the optic lobe and the brain of various invertebrate species. In some species it has also been shown that melatonin is produced rhythmically with high concentrations reached during the dark period. Moreover, the physiological effects of melatonin on various periodic processes such as rhythmic contractions in coelenterates, fissioning of asexual planarians or reproductive events in flies have been reported in the literature. All these results support the hypothesis (refs 36, 37) that melatonin is not solely a pineal hormone but that it may be an evolutionary conservative molecule principally involved in the transduction of photoperiodic information in all living organisms.     

Standards of evidence and causality in regulatory science: Risk and benefit assessment

In this paper we analyze the Russo-Williamson Thesis (RWT) as a standard of evidence in regulatory science, in risk as well as benefit assessment. In our analysis we take account of the recent controversies that have taken place in regulation with respect to the evidentiary requirements necessary for regulatory decision making. RWT's main point is that not only probabilistic but also mechanistic evidence is necessary for being able to infer the existence of causal links. We ask in which way RWT could have an impact upon current decision making about subjecting to regulation (or, to the contrary, leaving them unregulated) certain chemical substances, food stuffs, health claims, and other typical objects of regulation. We show that the application of RWT resolves some of the problems posed by current standards of evidence. RWT makes it possible to determine with higher accuracy if a particular substance should be subjected to regulation or not, even though under certain circumstances RWT itself may turn into a source of regulatory error. The adequacy of RWT as a standard of evidence depends on the precise manner of its application to regulation (particularly the consideration of mechanistic evidence as a complementary or necessary requirement), as well as the assessment of its non-epistemic consequences.     

Microbial energetics applied to waste repositories

Summary Through their catalytic abilities microbes can increase rates of chemical reactions which would take a very long time to reach equilibrium under abiotic conditions. Microbes also alter the concentration and composition of chemicals in the environment, thereby creating new conditions for further biological and chemical reactions. Rates of degradation and possible indirect consequences on leaching rates in waste repositories are a function of the presence or absence of microbes and of the conditions which allow them to become catalytically active.Microbially mediated reactions are no exception to the rule that all chemical processes are basically governed by thermodynamic laws. Naturally occurring processes proceed in the direction that leads to the minimal potential energy level attained when equilibrium is reached. A continuous supply of energy to an ecosystem in the form of biochemically unstable compounds maintains non-equilibrium conditions, a prerequisite for all chemotrophic life. Energy is released as a chemical reaction progresses towards equilibrium. Microbes scavenge that portion of the free energy of reaction (G_r) which can be converted into biochemically usable forms during the chemical oxidation processes. As electrontransfer catalysts, the microorganisms mediate reactions which are thermodynamically possible thereby stimulating reaction rates. Decomposition and mineralization in systems without a continuous supply of substrates and oxidants will lead to equilibria with minimal free energy levels at which point further microbial action would cease. The differences in the free energy levels of reactions (G_r), represent the maximal energy which is available to microorganisms for maintenance and growth. How much of the released free energy will be conserved in energy-rich bonds, compounds (e.g. ATP), and chemical potentials (e.g. emf) useful for biosynthesis and biological work is characteristic for the microbes involved and the processes and metabolic routes employed.Materials whose elements are not present in the most oxidized form attainable in the oxic environment of our planet are potentially reactive. Microbial activities are associated only with chemical reactions whose free energy changes are exergonic. This should be kept in mind for all investigations related to the role of microbes in repositories or in the layout of proper waste storage conditions. Rigorous application of thermodynamic concepts to environmental microbiology allows one to develop models and design experiments which are often difficult to conceive of in complex natural systems from physiological information alone. Thermodynamic considerations also aid in selecting proper deposition conditions and in carrying out thoughtful experiments in areas related to microbial ecology of waste repositories.     

Insect behavior at the leaf surface and learning as aspects of host plant selection

Summary Direct observations on the feeding behavior of insect herbivores are uncommon, but important. The important aspects of host-plant selection by phytophagous insects that have been revealed by such observations are the role of chemicals in the leaf surface, and learning. There are few detailed reports of behavior at the leaf surface, but these indicate that many, if not all, insects exhibit behavior pattenrs that can be interpreted as an examination of the quality of the surface and acceptance or rejection may follow without further testing. A number of experiments show that chemicals from the leaf surface commonly contribute to the acceptability or otherwise of a plant and in most cases so far the active chemicals are of widespread occurrence, not having a specific association with the host plant. Some experiments show that the association between surface chemicals and plant palatability is learned, but in other cases there is evidence of an innate response. Habituation to deterrent chemicals has been demonstrated in the laboratory, but not in the field. Food aversion learning also occurs and may be important in dietary switching by polyphagous insects.     

The effects of environmental hormones on reproduction

Considerable attention has been given in the past few years to the possibility that man-made chemicals (xenobiotics) in the environment may pose a hazard to human reproductive health. The endocrine-disrupting effects of many xenobiotics can be interpreted as interference with the normal regulation of reproductive processes by steroid hormones. Evidence reviewed here indicates that xenobiotics bind to androgen and oestrogen receptors in target tissues, and to androgen-binding protein and to sex hormone-binding globulin. Although environmental chemicals have weak hormonal activity, their ability to interact with more than one steroid-sensitive pathway provides a mechanism by which their hazardous nature can be augmented. A given toxicant may be present in low concentration in the environment and, therefore, harmless. However, we are not exposed to one toxicant at a time, but, rather, to all of the xenobiotics present in the environment. Therefore, numerous potential agonists/antagonists working together through several steroid-dependent signalling pathways could prove to be hazardous to human reproductive health. Received 25 March 1998; received after revision 15 June 1998; accepted 15 June 1998     

Exopolysaccharide production byVolcaniella eurihalina

The application of microbial extracellular polymers began in the 1960s, and since then there has been a remarkable increase in their commercial use. They are used in the food, textile, pharmaceutical, agricultural, paint and petroleum industries.Volcaniella eurihalina, a moderately halophilic eubacterium, produces an extracellular polysaccharide whose physical and chemical properties could be of interest for various industrial applications. The aim of this investigation is to analyze the different environmental parameters which influence the production of polysaccharide, and to study its chemical composition and the rheological properties of its solutions.     

Defensive use of an acquired substance (carminic acid) by predaceous insect larvae

Larvae of two insects, a coccinellid beetle (Hyperaspis trifurcata) and a chamaemyiid fly (Leucopis sp.), feed on cochineal insects and appropriate their prey's defensive chemical, carminic acid, for protective purposes of their own.H. trifurcata discharges the chemical with droplets of blood (hemolymph) that it emits when disturbed;Leucopis sp. ejects the compound with rectal fluid. Ants are thwarted by these defenses, which are compared with the previously-described defense of a pyralid caterpillar (Laetilia coccidivora) that disgorges carminic acid-laden crop fluid. The defensive fluid of all three larvae contains carminic acid at concentrations spanning a range (0.2–6.2%) proven deterrent to ants. Many insects are known to appropriate defensive substances from plants. Insects that acquire defensive chemicals from animal sources may be relatively rare.Paper No. 124 in the series Defense Mechanisms of Arthropods; No. 123 is Epstein et al., J. Lepid. Soc. (in press).     

Minisatellite instability and germline mutation

Tandem-repeat DNA actively turns over in the genome by a variety of poorly understood dynamic mechanisms. Minisatellites, a class of tandem repeats, have been shown to cause disease by influencing gene expression, modifying coding sequences within genes or generating fragile sites. There has been recent rapid progress towards understanding molecular turnover processes at human minisatellites. Instability at GC-rich minisatellites appears to involve distinct mutation processes operating in somatic and germline cells. In the germline, complex conversion-like events occur, probably during meiosis. Repeat turnover appears to be controlled by intense recombinational activity in DNA flanking the repeat array, suggesting that minisatellites might evolve as by-products of localised meiotic recombination in the human genome. In contrast, AT-rich minisatellites appear to evolve by intra-allelic processes such as replication slippage. Curiously, minisatellites in other organisms appear to be more stable than their human counterparts, suggesting species-specific differences in turnover processes. Some yeast models display human-like minisatellite turnover processes at meiosis. However, all attempts to transfer human germline instability to transgenic mice have failed. Finally, tandem repeat instability in various species appears to be extremely sensitive to environmental agents such as radiation via a mechanism which remains enigmatic.     

Functional interplay between tetraspanins and proteases

Several recent publications have described examples of physical and functional interations between tetraspanins and specific membrane proteases belonging to the TM-MMP and α-(ADAMs) and γ-secretases families. Collectively, these examples constitute an emerging body of evidence supporting the notion that tetraspanin-enriched microdomains (TEMs) represent functional platforms for the regulation of key cellular processes including the release of surface protein ectodomains ("shedding"), regulated intramembrane proteolysis ("RIPing") and matrix degradation and assembly. These cellular processes in turn play a crucial role in an array of physiological and pathological phenomena. Thus, TEMs may represent new therapeutical targets that may simultaneously affect the proteolytic activity of different enzymes and their substrates. Agonistic or antagonistic antibodies and blocking soluble peptides corresponding to tetraspanin functional regions may offer new opportunities in the treatment of pathologies such as chronic inflammation, cancer, or Alzheimer's disease. In this review article, we will discuss all these aspects of functional regulation of protease activities by tetraspanins.     

Regulation of microRNA biogenesis and turnover by animals and their viruses

MicroRNAs (miRNAs) are a ubiquitous component of gene regulatory networks that modulate the precise amounts of proteins expressed in a cell. Despite their small size, miRNA genes contain various recognition elements that enable specificity in when, where and to what extent they are expressed. The importance of precise control of miRNA expression is underscored by functional studies in model organisms and by the association between miRNA mis-expression and disease. In the last decade, identification of the pathways by which miRNAs are produced, matured and turned-over has revealed many aspects of their biogenesis that are subject to regulation. Studies in viral systems have revealed a range of mechanisms by which viruses target these pathways through viral proteins or non-coding RNAs in order to regulate cellular gene expression. In parallel, a field of study has evolved around the activation and suppression of antiviral RNA interference (RNAi) by viruses. Virus encoded suppressors of RNAi can impact miRNA biogenesis in cases where miRNA and small interfering RNA pathways converge. Here we review the literature on the mechanisms by which miRNA biogenesis and turnover are regulated in animals and the diverse strategies that viruses use to subvert or inhibit these processes.     

Epithelial antimicrobial peptides: innate local host response elements

Multicellular organisms have to survive in an environment laden with numerous microorganisms, which represent a potential hazard to life. Different strategies have been developed to ward off infections by preventing microorganisms from entering surfaces and by preventing the attack of microorganisms that have already entered the epithelia. Therefore, it is not surprising that epithelia are equipped with various antimicrobial substances that act rapidly to kill a broad range of microorganisms. This review summarizes our present knowledge about epithelial peptide antibiotics produced in plants, invertebrates, and vertebrates including humans. There is now strong evidence that in addition to constitutively secreted peptide antibiotics, others are induced upon contact with microorganisms or by proinflammatory cytokines. beta-Defensins represent one family of vertebrate antimicrobial peptides, members of which are inducible and have recently been identified in humans. The defensin-characteristic local expression pattern may indicate that specialized surfaces express a characteristic surface antimicrobial peptide pattern that might define the characteristic microflora as well as the density of microorganisms present on the surface.     

Role of p21-activated kinases in cardiovascular development and function

p21-activated kinases (Paks) are a group of six serine/threonine kinases (Pak1-6) that are involved in a variety of biological processes. Recently, Paks, more specifically Pak1, -2, and -4, have been shown to play important roles in cardiovascular development and function in a range of model organisms including zebrafish and mice. These functions include proper morphogenesis and conductance of the heart, cardiac contractility, and development and integrity of the vasculature. The mechanisms underlying these effects are not fully known, but they likely differ among the various Pak isoforms and include both kinase-dependent and -independent functions. In this review, we discuss aspects of Pak function relevant to cardiovascular biology as well as potential therapeutic implications of small-molecule Pak inhibitors in cardiovascular disease.