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Lethal
Kinds of Lethal Terms modified by Lethal Selected AbstractsThe commonly used marker ELAV is transiently expressed in neuroblasts and glial cells in the Drosophila embryonic CNSDEVELOPMENTAL DYNAMICS, Issue 12 2007Christian Berger Abstract Glial cells in the Drosophila embryonic nervous system can be monitored with the marker Reversed-polarity (Repo), whereas neurons lack Repo and express the RNA-binding protein ELAV (Embryonic Lethal, Abnormal Vision). Since the first description of the ELAV protein distribution in 1991 (Robinow and White), it is believed that ELAV is an exclusive neuronal and postmitotic marker. Looking at ELAV expression, we unexpectedly observed that, in addition to neurons, ELAV is transiently expressed in embryonic glial cells. Furthermore, it is transiently present in the proliferating longitudinal glioblast, and it is transcribed in embryonic neuroblasts. Likewise, elav -Gal4 lines, which are generally used as postmitotic neuronal driver lines, show expression in neural progenitor cells and nearly all embryonic glial cells. Thus, in the embryo, elav can no longer be considered an exclusive marker or driver for postmitotic neurons. elav loss-of-function mutants show no obvious effects on the number and pattern of embryonic glia. Developmental Dynamics 236:3562,3568, 2007. © 2007 Wiley-Liss, Inc. [source] Lethal and sublethal effects of polychlorinated biphenyls on Rana sylvatica tadpolesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2002Wesley K. Savage Abstract In static experiments, we exposed tadpoles of the wood frog (Rana sylvatica) to sediment collected from a riverine wetland in the St. Lawrence River basin that is highly contaminated with polychlorinated biphenyls (PCBs). Significant mortality occurred early in the experiment and was not explained by a simple dose-dependent relationship. Direct sediment contact resulted in higher tadpole mortality compared with tadpoles suspended in mesh containers above the sediment. Sublethal effects of exposure were also apparent, characterized by behavioral abnormalities, including reduced activity levels and swimming speed, that differed depending on whether tadpoles were in contact with or suspended above the sediment. We demonstrate in this experiment that PCB-contaminated sediment induced significant mortality and behavioral dysfunction in early development, but the effects on natural populations existing in the contaminated region is not known. [source] Lethal and non-lethal effects of multiple indigenous predators on the invasive golden apple snail (Pomacea canaliculata)FRESHWATER BIOLOGY, Issue 10 2004Nils Carlsson Summary 1. We investigated the individual and combined effects of two predators (the climbing perch, Anabas testudineus, and the wetland crab, Esanthelphusa nimoafi) indigenous to wetlands in Laos, on the behaviour and survival of the invasive South American golden apple snail (Pomacea canaliculata). The snail is considered a pest, consuming large amounts of rice and other aquatic vegetation in the region. 2. Snail avoidance reactions to released predator chemical cues were investigated in aquaria while the effects of predators on a mixed snail population were studied in field enclosures that contained native aquatic plants (Salvinia cucullata, Ludwigia adscendens and Ipomoea aquatica). 3. In the aquaria experiment, neonate (2,3 mm) and medium-sized snails (8,10 mm) responded to fish chemical cues by going to the surface, whereas adult snails (35,40 mm) went to the bottom. In contrast, no size class of snails reacted to chemical cues released by crabs. 4. In the field experiment, fish reduced the abundance of neonate snails, and crabs reduced the abundance of all size classes. The effect of the combined predators could not be predicted from the mortality rate observed in single predator treatments. The survival of neonate and medium-sized snails was greater and of adults less than expected. The presence of predators did not affect egg production. Snails consumed significant amounts of plants despite the presence of predators. 5. Our findings suggest that some indigenous Asian predators have lethal and sublethal effects on P. canaliculata that depend on snail size and predator type. When in the presence of several predators the response of snails to one predator may either increase or decrease the vulnerability of snails to the others. [source] Species-specific limitation of vole population growth by least weasel predation: facilitation of coexistence?OIKOS, Issue 1 2008Elina Koivisto Interspecific competition is usually understood as different species competing directly with each other for limited resources. However, predators can alter such competitive interactions substantially. Predation can promote the coexistence of species in a situation where it would otherwise be impossible, for example if a tradeoff between the competitive abilities and predation resistance of the prey species exists. The field vole Microtus agrestis and the sibling vole M. rossiaemeridionalis are sympatric grassland species, which compete for the same resources. At the population level sibling voles are suggested to be superior competitors to field voles, yet more vulnerable to predation. We tested the effects of predation on the two species in 0.5 ha outdoor enclosures by exposing vole populations to radio-collared freely-hunting least weasels Mustela nivalis nivalis for three weeks. Lethal and non-lethal impacts of predation limited population densities of both species during and after the experimental period, but the effect was more pronounced in sibling voles in which population densities decreased markedly during the treatment period and even after that. Field vole population densities remained stable under weasel predation, while densities increased in controls. Survival in both species was lower in treatment populations compared to controls, but the effect tended to be more pronounced in sibling voles and in females of both species. The average mass of adults in both species declined in the treatment populations. These results suggest that predation by least weasels can limit vole populations locally, even during favourable summer conditions, and have extended negative effects on the dynamics of vole populations. In addition, predation alleviated interspecific competition between the vole species and is, therefore, a potential factor enabling the coexistence of them. [source] Lethal and sub-lethal effects of spinosad on bumble bees (Bombus impatiens Cresson)PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 7 2005Lora A Morandin Abstract Recent developments of new families of pesticides and growing awareness of the importance of wild pollinators for crop pollination have stimulated interest in potential effects of novel pesticides on wild bees. Yet pesticide toxicity studies on wild bees remain rare, and few studies have included long-term monitoring of bumble bee colonies or testing of foraging ability after pesticide exposure. Larval bees feeding on exogenous pollen and exposed to pesticides during development may result in lethal or sub-lethal effects during the adult stage. We tested the effects of a naturally derived biopesticide, spinosad, on bumble bee (Bombus impatiens Cresson) colony health, including adult mortality, brood development, weights of emerging bees and foraging efficiency of adults that underwent larval development during exposure to spinosad. We monitored colonies from an early stage, over a 10-week period, and fed spinosad to colonies in pollen at four levels: control, 0.2, 0.8 and 8.0 mg kg,1, during weeks 2 through 5 of the experiment. At concentrations that bees would likely encounter in pollen in the wild (0.2,0.8 mg kg,1) we detected minimal negative effects to bumble bee colonies. Brood and adult mortality was high at 8.0 mg kg,1 spinosad, about twice the level that bees would be exposed to in a ,worst case' field scenario, resulting in colony death two to four weeks after initial pesticide exposure. At more realistic concentrations there were potentially important sub-lethal effects. Adult worker bees exposed to spinosad during larval development at 0.8 mg kg,1 were slower foragers on artificial complex flower arrays than bees from low or no spinosad treated colonies. Inclusion of similar sub-lethal assays to detect effects of pesticides on pollinators would aid in development of environmentally responsible pest management strategies. Copyright © 2005 Society of Chemical Industry [source] Variation in Pesticide Tolerance of Tadpoles among and within Species of Ranidae and Patterns of Amphibian DeclineCONSERVATION BIOLOGY, Issue 5 2000Christine M. Bridges Because variability exists among organisms in their sensitivity to environmental stressors, it is important to determine the degree of this variation when undertaking conservation efforts. We conducted both lethal (time-to-death) and sublethal (activity change) assays to determine the degree of variation in the sensitivity of tadpoles to a pesticide, carbaryl, at three hierarchical levels: among ranid species, among several populations of a single ranid species ( Rana sphenocephala), and within populations of R. sphenocephala. We observed significant variation in time to death among the nine ranid species and among the 10 R. sphenocephala populations we tested. Four out of eight R. sphenocephala populations exhibited significantly different times to death among families. The magnitude of the activity change in response to exposure to sublethal carbaryl levels was significantly different among species and within R. sphenocephala populations. Chemical contamination, at lethal or sublethal levels, can alter natural regulatory processes such as juvenile recruitment in amphibian populations and should be considered a contributing cause of declines in amphibian populations. Resumen: Existe una variación significativa entre y dentro de especies de anfibios con respecto a los reportes de disminuciones poblacionales; las especies en disminución son frecuentemente encontradas en ambientes que son fisiográficamente similares a ambientes donde las mismas especies están prosperando. Debido a que la variabilidad existe entre organismos en lo referente a su sensibilidad a estresores ambientales, es importante determinar el grado de esta variación cuando se lleven a cabo esfuerzos de conservación. Nosotros llevamos a cabo ensayos tanto letales (tiempo de muerte) como subletales (cambios de actividad) para determinar el grado de variación en la sensibilidad de renacuajos a un pesticida, carbaryl, en tres niveles jerárquicos: entre especies de ránidos, entre diversas poblaciones de una sola especie de ránido ( Rana sphenocephala) y dentro de poblaciones de R. sphenocephala. Observamos diferencias significativas en tiempo de muerte entre las nueve especies de ránidos y entre las 10 poblaciones de R. sphenocephala evaluadas. Cuatro de ocho poblaciones de R. sphenocephala exhibieron tiempos de muerte significativamente diferentes entre familias. La magnitud del cambio de actividad al ser expuestas a niveles subletales de carbaryl fue significativamente diferente entre especies y dentro de poblaciones de R. sphenocephala. La contaminación química, a niveles letales y subletales, puede alterar los procesos reguladores naturales (por ejemplo el reclutamiento de juveniles) en poblaciones de anfibios y debería ser considerado como una causa que contribuye a la disminución de poblaciones de anfibios. [source] Mutagenesis of ,-tubulin cysteine residues in Saccharomyces cerevisiae: Mutation of cysteine 354 results in cold-stable microtubulesCYTOSKELETON, Issue 2 2001Mohan L. Gupta Jr. Abstract Cysteine residues play important roles in the control of tubulin function. To determine which of the six cysteine residues in ,-tubulin are critical to tubulin function, we mutated the cysteines in Saccharomyces cerevisiae ,-tubulin individually to alanine and serine residues. Of the twelve mutations, only three produced significant effects: C12S, C354A, and C354S. The C12S mutation was lethal in the haploid, but the C12A mutation had no observable phenotype. Based on interactive views of the electron crystallographic structure of tubulin, we suggest that substitution of serine for cysteine at this position has a destabilizing effect on the interaction of tubulin with the exchangeable GTP. The two C354 mutations, although not lethal, produced dramatic effects on microtubules and cellular processes that require microtubules. The C354 mutant cells had decreased growth rates, a slowed mitosis, increased resistance to benomyl, and impaired nuclear migration and spindle assembly. The C354A mutation produced a more severe phenotype than the C354S mutation: the haploid cells had chromosome segregation defects, only 50% of cells in a culture were viable, and a significant percentage of the cells were misshapened. Cytoplasmic microtubules in the C354S and C354A cells were longer than in the control strain and spindle structures appeared shorter and thicker. Both cytoplasmic and spindle microtubules in the two C354 mutants were extremely stable to cold temperature. After 24 h at 4°C, the microtubules were still present and, in fact, very long and thick tubulin polymers had formed. Evidence exists to indicate that the C354 residue in mammalian tubulin is near the colchicine binding site and the electron crystal structure of tubulin places the residue at the interface between the ,- and ,-subunits. The sulfhydryl group is situated in a polar environment, which may explain why the alanine mutation is more severe than the serine mutation. When the C12S and the two C354 mutations were made in a diploid strain, the mutated tubulin was incorporated into microtubules and the resulting heterozygotes had phenotypes that were intermediate between those of the mutated haploids and the wild-type strains. The results suggest that the C12 and C354 residues play important roles in the structure and function of tubulin. Cell Motil. Cytoskeleton 49:67,77, 2001. © 2001 Wiley-Liss, Inc. [source] Planar cell polarity effector gene Fuzzy regulates cilia formation and Hedgehog signal transduction in mouseDEVELOPMENTAL DYNAMICS, Issue 12 2009Westley Heydeck Abstract Precise planar cell polarity (PCP) is critical for the development of multiple organ systems in animals. A group of core-PCP proteins are recognized to play crucial roles in convergent extension and other PCP-related processes in mammals. However, the functions of another group of PCP-regulating proteins, the PCP-effector proteins, are yet to be fully studied. In this study, the generation and characterization of a mouse mutant for the PCP effector gene Fuzzy (Fuz) is reported. Fuz homozygous mutants are embryonically lethal, with multiple defects including neural tube defects, abnormal dorsal/ventral patterning of the spinal cord, and defective anterior/posterior patterning of the limb buds. Fuz mutants also exhibit abnormal Hedgehog (Hh) signaling and inefficient proteolytic processing of Gli3. Finally, a significant decrease in cilia was found in Fuz homozygous mutants. In conclusion, Fuz plays an important role in cilia formation, Hh signal transduction, and embryonic development in mammals. Developmental Dynamics 238:3035,3042, 2009. © 2009 Wiley-Liss, Inc. [source] PDGFR-, signaling is critical for tooth cusp and palate morphogenesisDEVELOPMENTAL DYNAMICS, Issue 1 2005Xun Xu Abstract Platelet-derived growth factor receptor alpha (PDGFR-,) and PDGF ligands are key regulators for embryonic development. Although Pdgfr, is spatially expressed in the cranial neural crest (CNC)-derived odontogenic mesenchyme, mice deficient for Pdgfr, are embryonic lethal, making it impossible to investigate the functional significance of PDGF signaling in regulating the fate of CNC cells during tooth morphogenesis. Taking advantage of the kidney capsule assay, we investigated the biological function of PDGF signaling in regulating tooth morphogenesis. Pdgfr, and Pdgfa are specifically and consistently expressed in the CNC-derived odontogenic mesenchyme and the dental epithelium, respectively, throughout all stages of tooth development, suggesting a paracrine function of PDGF signaling in regulating tooth morphogenesis. Highly concentrated expression patterns of Pdgfr, and Pdgfa are associated with the developing dental cusp, suggesting possible functional importance of PDGF signaling in regulating cusp formation. Loss of the Pdgfr, gene does not affect proper odontoblasts proliferation and differentiation in the CNC-derived odontogenic mesenchyme but perturbs the formation of extracellular matrix and the organization of odontoblast cells at the forming cusp area, resulting in dental cusp growth defect. Pdgfr,,/, mice have complete cleft palate. We show that the cleft palate in Pdgfr, mutant mice results from an extracellular matrix defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Collectively, our data suggests that PDGFR, and PDGFA are critical regulators for the continued epithelial,mesenchymal interaction during tooth and palate morphogenesis. Disruption of PDGFR, signaling disturbs the growth of dental cusp and interferes with the critical extension of palatal shelf during craniofacial development. Developmental Dynamics 232:75,84, 2005. © 2004 Wiley-Liss, Inc. [source] Genome-wide P -element screen for Drosophila synaptogenesis mutantsDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2006Faith L.W. Liebl Abstract A molecular understanding of synaptogenesis is a critical step toward the goal of understanding how brains "wire themselves up," and then "rewire" during development and experience. Recent genomic and molecular advances have made it possible to study synaptogenesis on a genomic scale. Here, we describe the results of a screen for genes involved in formation and development of the glutamatergic Drosophila neuromuscular junction (NMJ). We screened 2185 P -element transposon mutants representing insertions in ,16% of the entire Drosophila genome. We first identified recessive lethal mutants, based on the hypothesis that mutations causing severe disruptions in synaptogenesis are likely to be lethal. Two hundred twenty (10%) of all insertions were homozygous lethal. Two hundred five (93%) of these lethal mutants developed at least through late embryogenesis and formed neuromusculature. We examined embryonic/larval NMJs in 202 of these homozygous mutants using immunocytochemistry and confocal microscopy. We identified and classified 88 mutants with altered NMJ morphology. Insertion loci in these mutants encode several different types of proteins, including ATP- and GTPases, cytoskeletal regulators, cell adhesion molecules, kinases, phosphatases, RNA regulators, regulators of protein formation, transcription factors, and transporters. Thirteen percent of insertions are in genes that encode proteins of novel or unknown function. Complementation tests and RT-PCR assays suggest that approximately 51% of the insertion lines carry background mutations. Our results reveal that synaptogenesis requires the coordinated action of many different types of proteins,perhaps as much as 44% of the entire genome,and that transposon mutageneses carry important caveats that must be respected when interpreting results generated using this method. © 2006 Wiley Periodicals, Inc. J Neurobiol, 2006 [source] Dopamine and sensory tissue development in Drosophila melanogasterDEVELOPMENTAL NEUROBIOLOGY, Issue 4 2001Wendi Neckameyer Abstract Dopamine is an important signaling molecule in the nervous system; it also plays a vital role in the development of diverse non-neuronal tissues in the fruit fly Drosophila melanogaster. The current study demonstrates that males depleted of dopamine as third instar larvae (via inhibition of the biosynthetic enzyme tyrosine hydroxylase) demonstrated abnormalities in courtship behavior as adults. These defects were suggestive of abnormalities in sensory perception and/or processing. Electroretinograms (ERGs) of eyes from adults depleted of dopamine for 1 day as third instar larvae revealed diminished or absent on- and off-transients. These sensory defects were rescued by the addition of L -DOPA in conjunction with tyrosine hydroxylase inhibition during the larval stage. Depletion of dopamine in the first or second larval instar was lethal, but this was not due to a general inhibition of proliferative cells. To establish that dopamine was synthesized in tissues destined to become part of the adult sensory apparatus, transgenic lines were generated containing 1 or 4 kb of 5, upstream sequences from the Drosophila tyrosine hydroxylase gene (DTH) fused to the E. coli ,-galactosidase reporter. The DTH promoters directed expression of the reporter gene in discrete and consistent patterns within the imaginal discs, in addition to the expected expression in gonadal, brain, and cuticular tissues. The ,-galactosidase expression colocalized with tyrosine hydroxylase protein. These results are consistent with a developmental requirement for dopamine in the normal physiology of adult sensory tissues. © 2001 John Wiley & Sons, Inc. J Neurobiol 47: 280,294, 2001 [source] Insulin resistance, diabetes and cardiovascular risk: approaches to treatmentDIABETES OBESITY & METABOLISM, Issue 6 2005Daniel E. Rosenberg Abstract:, The prevalence of diabetes is increasing worldwide. Insulin resistance and diabetes mellitus are major predictors of cardiovascular ischaemic disease. Other risk factors for cardiovascular death including hypertension, dyslipidaemia, smoking and visceral obesity are especially lethal in diabetics. C-reactive protein, plasminogen activator inhibitor-1, matrix metalloproteinases and other emerging risk factors and their roles are continually being researched and discovered. Treatment of this syndrome must be aimed at lifestyle modification, glycaemic control and management of concomitant risk factors. Diet and exercise play a vital role in the treatment of diabetes and the metabolic syndrome. Weight reduction and increased physical activity will improve insulin resistance, hyperglycaemia, hypertension and dyslipidaemia. Hypertension management has been shown to be especially important in diabetics to prevent cardiovascular events. Likewise, multiple clinical trials show that reduction of cholesterol is even more vital in diabetics than the general population for risk reduction of coronary disease. There is a great deal of evidence that tight control of glycaemia is essential to treatment of this condition. There are a variety of available pharmacological agents available including metformin, insulin secretagogues, alpha-glucosidase inhibitors, thiazolidinediones and insulin. The mechanisms and side effects of these medications are discussed. As macrovascular disease is the major cause of morbidity and mortality, an early, aggressive, multi-factorial approach to treatment of the metabolic syndrome and diabetes is vital to prevent adverse cardiac outcomes. [source] Networks and dominance hierarchies: does interspecific aggression explain flower partitioning among stingless bees?ECOLOGICAL ENTOMOLOGY, Issue 2 2010KAI DWORSCHAK 1. The distribution of consumers among resources (trophic interaction network) may be shaped by asymmetric competition. Dominance hierarchy models predict that asymmetric interference competition leads to a domination of high quality resources by hierarchically superior species. 2. In order to determine the competitive dominance hierarchy and its effect on flower partitioning in a local stingless bee community in Borneo, interspecific aggressions were tested among eight species in arena experiments. 3. All species tested were strongly mutually aggressive in the arena, and the observed interactions were often lethal for one or both opponents. Aggression significantly increased with body size differences between fighting pairs and was asymmetric: larger aggressors were superior over smaller species. Additional aggression tests involved dummies with surface extracts, and results suggest that species- and colony-specific surface profiles are important in triggering the aggressive behaviour. 4. Sixteen stingless bee species were observed foraging on 41 species of flowering plants. The resulting bee,flower interaction network showed a high degree of generalisation (network-level specialisation H2' = 0.11), corresponding to a random, opportunistic distribution of bee species among available flower species. 5. Aggressions on flowers were rare and only occurred at a low level. The dominance hierarchy obtained in the arena experiments did not correlate significantly with plant quality, estimated as the number of flowers per plant or as total bee visitation rate. 6. Our findings suggest that asymmetries in interference competition do not necessarily translate into actual resource partitioning in the context of complex interacting communities. [source] Post-ingestive effects of nectar alkaloids depend on dominance status of bumblebeesECOLOGICAL ENTOMOLOGY, Issue 4 2009JESSAMYN S. MANSON Abstract 1.,Secondary metabolites have acute or chronic post-ingestive effects on animals, ranging from death to growth inhibition to reduced nutrient assimilation. 2.,Although characterised as toxic, the nectar of Gelsemium sempervirens is not lethal to pollinators, even when the concentration of the nectar alkaloid gelsemine is very high. However, little is known about the sublethal costs of nectar alkaloids. 3.,Using a microcolony assay and paired worker bumblebees, the present study measured the effects of artificial nectar containing gelsemine on oocyte development. Oocytes are a sensitive indicator of protein utilisation and general metabolic processes. We also calculated carbohydrate concentrations in the haemolymph to examine energetic costs of gelsemine consumption. 4.,High concentrations of gelsemine significantly reduced mean oocyte width in subordinate bees, while dominant bees showed only a trend towards oocyte inhibition. Gelsemine consumption did not reduce carbohydrate concentrations in haemolymph. 5.,The cost of ingesting gelsemine may be due to direct toxicity of alkaloids or may be an expense associated with detoxifying gelsemine. Detoxification of alkaloids can require reallocation of resources away from essential metabolic functions like reproduction. The risks associated with nectar alkaloid consumption are tied to both the social and nutritional status of the bee. [source] Thermal biology of the meadow grasshopper, Chorthippus parallelus, and the implications for resistance to diseaseECOLOGICAL ENTOMOLOGY, Issue 6 2005Simon Springate Abstract., 1.,The thermal biology of the meadow grasshopper, Chorthippus parallelus, a common, habitat generalist acridid species found in the U.K., was characterised and the influence of thermoregulatory behaviour for resistance against a temperate (Beauveria bassiana) and tropical (Metarhizium anisopliae var. acridum) fungal pathogen was determined. 2.,Chorthippus parallelus was found to be an active behavioural thermoregulator, with a preferred temperature range of 32,35 °C. 3.,Both pathogens proved lethal to fifth instar and adult grasshoppers. No evidence of behavioural fever in response to infection by either pathogen was found, but normal thermoregulation was found to reduce virulence and spore production of B. bassiana. Normal thermoregulation did not appear to affect M. anisopliae var. acridum. 4.,These results suggest that the effects of temperature on host resistance depend on the thermal sensitivity of the pathogen and, in this case, derive from direct effects of temperature on pathogen growth rather than indirect effects mediated by host immune response. 5.,The implications for possible risks of exotic pathogens and influence of climate change are discussed. [source] Chromosomal antioxidant genes have metal ion-specific roles as determinants of bacterial metal toleranceENVIRONMENTAL MICROBIOLOGY, Issue 10 2009Joe J. Harrison Summary Microbiological metal toxicity involves redox reactions between metal species and cellular molecules, and therefore, we hypothesized that antioxidant systems might be chromosomal determinants affecting the susceptibility of bacteria to metal toxicity. Here, survival was quantified in metal ion-exposed planktonic cultures of several Escherichia coli strains, each bearing a mutation in a gene important for redox homeostasis. This characterized ,250 gene,metal combinations and identified that sodA, sodB, gor, trxA, gshA, grxA and marR have distinct roles in safeguarding or sensitizing cells to different toxic metal ions (Cr2O72,, Co2+, Cu2+, Ag+, Zn2+, AsO2,, SeO32, or TeO32,). To shed light on these observations, fluorescent sensors for reactive oxygen species (ROS) and reduced thiol (RSH) quantification were used to ascertain that different metal ions exert oxidative toxicity through disparate modes-of-action. These oxidative mechanisms of metal toxicity were categorized as involving ROS and thiol-disulfide chemistry together (AsO2,, SeO32,), ROS predominantly (Cu2+, Cr2O72,) or thiol-disulfide chemistry predominantly (Ag+, Co2+, Zn2+, TeO32,). Corresponding to this, promoter- luxCDABE fusions showed that toxic doses of different metal ions up- or downregulate the transcription of gene sets marking distinct pathways of cellular oxidative stress. Altogether, our findings suggest that different metal ions are lethal to cells through discrete pathways of oxidative biochemistry, and moreover, indicate that chromosomally encoded antioxidant systems may have metal ion-specific physiological roles as determinants of bacterial metal tolerance. [source] Effect of in vitro and in vivo organotin exposures on the immune functions of murray cod (Maccullochella peelii peelii)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Andrew J. Harford Abstract Murray cod (Maccullochella peelii peelii) is an iconic native Australian freshwater fish and an ideal species for ecotoxicological testing of environmental pollutants. The species is indigenous to the Murray-Darling basin, which is the largest river system in Australia but also the ultimate sink for many environmental pollutants. The organotins tributyltin (TBT) and dibutyltin (DBT) are common pollutants of both freshwater and marine environments and are also known for their immunotoxicity in both mammals and aquatic organisms. In this study, TBT and DBT were used as exemplar immunotoxins to assess the efficiency of immune function assays (i.e., mitogen-stimulated lymphoproliferation, phagocytosis in head kidney tissue, and serum lysozyme activity) and to compare the sensitivity of Murray cod to other fish species. The organotins were lethal to Murray cod at concentrations previously reported as sublethal in rainbow trout (i.e., intraperitoneal [i.p.] lethal dose to 75% of the Murray cod [LD75] = 2.5 mg/kg DBT and i.p. lethal dose to 100% of the Murray cod [LD100] = 12.5 mg/kg TBT and DBT). In vivo TBT exposure at 0.1 and 0.5 mg/kg stimulated the phagocytic function of Murray cod (F = 6.89, df = 18, p = 0.004), while the highest concentration of 2.5 mg/kg TBT decreased lymphocyte numbers (F = 7.92, df = 18, p = 0.02) and mitogenesis (F = 3.66, df = 18, p = 0.035). Dibutyltin was the more potent immunosuppressant in Murray cod, causing significant reductions in phagocytic activity (F = 5.34, df = 16, p = 0.013) and lymphocyte numbers (F = 10.63, df = 16, p = 0.001). [source] Influence of duration of exposure to the pyrethroid fenvalerate on sublethal responses and recovery of Daphnia magna strausENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2005Sebastián Reynaldi Abstract This study compares lethal and sublethal responses of Daphnia magna Straus exposed to fenvalerate continuously (21 d) and as a pulse (24 h). Survival was reduced more severely in the continuous- than in the pulse-exposure regime. Complete mortality occurred at 1 ,g/L for continuous exposure and at 3.2 ,g/L for pulse exposure. Regarding reproductive endpoints, fenvalerate delayed the age at first reproduction. At the beginning of the reproductive phase (day 10), this delay resulted in a reduction of the neonates per living female at similar concentrations in both exposure regimes (0.3 and 0.1 ,g/L for continuous and pulse exposure, respectively). The population growth rate was inhibited in continuous and pulse exposure at 0.3 and 0.6 ,g/L, respectively. However, the effects of fenvalerate in the pulse exposure were transient. After 21 d, a recovery to values close to the controls occurred with respect to the total neonates per female and the population growth rate over a broad range of concentrations from 0.1 up to 1 ,g/L. In contrast, no substantial recovery occurred in the continuous-exposure regime. [source] Synergistic impacts of malathion and predatory stress on six species of North American tadpolesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2004Rick A. Relyea Abstract The decline of many amphibian populations is associated with pesticides, but for most pesticides we know little about their toxicity to amphibians. Malathion is a classic example; it is sprayed over aquatic habitats to control mosquitoes that carry malaria and the West Nile virus, yet we know little about its effect on amphibians. I examined the survival of six species of tadpoles (wood frogs, Rana sylvatica; leopard frogs, R. pipiens; green frogs, R. clamitans; bullfrogs, R. catesbeiana; American toads, Bufo americanus; and gray tree frogs, Hyla versicolor) for 16 d in the presence or absence of predatory stress and six concentrations of malathion. Malathion was moderately toxic to all species of tadpoles (median lethal concentration [LC50] values, the concentration estimated to kill 50% of a test population, ranged from 1.25,5.9 mg/L). These values are within the range of values reported for the few amphibians that have been tested (0.2,42 mg/L). In one of the six species, malathion became twice as lethal when combined with predatory stress. Similar synergistic interactions have been found with the insecticide carbaryl, suggesting that the synergy may occur in many carbamate and organophosphate insecticides. While malathion has the potential to kill amphibians and its presence is correlated with habitats containing declining populations, its actual role in amphibian declines is uncertain given the relatively low concentration in aquatic habitats. [source] The relative sensitivity of four benthic invertebrates to metals in spiked-sediment exposures and application to contaminated field sedimentENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 4 2003Danielle Milani Abstract The relative sensitivity of four benthic invertebrates (Hyalella azteca, Chironomus riparius, Hexagenia spp., and Tubifex tubifex) was determined for Cd, Cu, and Ni in water-only and in spiked-sediment exposures. Survival (median lethal concentrations [LC50s] and the concentrations estimated to be lethal to 25% of test organisms [LC25s]), and endpoints for growth and reproduction (mean inhibitory concentrations [IC25s]) were compared. The sensitivities differed depending on the species and metal, although some trends emerged. In water-only exposures, H. azteca is the most sensitive species to cadmium and nickel, with mean LC50s of 0.013 and 3.6 mg/L, respectively; C. riparius is the most sensitive species to copper, with a mean LC50 of 0.043 mg/L. In the spiked-sediment exposures, the order in decreasing sensitivity to copper is Hyalella = Hexagenia < Chironomus < Tubifex for survival and growth/reproduction. For cadmium, the order in decreasing sensitivity is Hyalella = Chironomus < Hexagenia < Tubifex, and for nickel is Hyalella , Hexagenia < Chironomus < Tubifex. Chironomus riparius and Hexagenia spp. survival can be used to distinguish between toxicity caused by different metals. Species test responses in field-collected sediment (Collingwood Harbour, ON, Canada) were examined in an attempt to determine the causative agent of toxicity throughout, using the established species sensitivities. Sediment toxicity was categorized first by comparing species responses to those established for a reference database. Test responses in the field-collected sediment do not support causality by Cu, a suspected toxicant based on comparison of sediment chemistry with sediment quality guidelines. [source] Altering cytochrome P4501A activity affects polycyclic aromatic hydrocarbon metabolism and toxicity in rainbow trout (Oncorhynchus mykiss)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2002Stephanie A. Hawkins Abstract The polycyclic aromatic hydrocarbons (PAHs) phenanthrene and retene (7-isopropyl-1-methyl phenanthrene) are lethal to rainbow trout (Oncorhynchus mykiss) larvae during chronic exposures. Phenanthrene is a low-toxicity, non-cytochrome P4501A (CYP1A),inducing compound that accumulates in fish tissues during exposure to lethal concentrations in water. Retene is a higher toxicity CYP1A-inducing compound that is not detectable in tissue at lethal exposure concentrations. The metabolism, excretion, and toxicity of retene and phenanthrene were examined in juvenile and larval rainbow trout during coexposure to the model CYP1A inducer ,-naphthoflavone (,NF), or to the inducer-inhibitor piperonyl butoxide to determine if modulating CYP1A activity affected PAH metabolism and toxicity. Phenanthrene metabolism, excretion rate, and toxicity increased with coexposure to ,NF. Piperonyl butoxide inhibited phenanthrene metabolism and reduced the excretion of all phenanthrene metabolites. As a consequence, embryo mortality rates increased but rates of sublethal effects did not. Coexposure of trout to retene and ,NF caused no change in retene metabolism and excretion, but retene toxicity increased, perhaps due to additivity. Piperonyl butoxide inhibited retene metabolism, decreased the excretion of some retene metabolites while increasing the excretion of others, and increased the toxicity of retene. These results support the role of CYP1A activity in PAH metabolism and excretion, and the role of the CYP1A-generated metabolites of PAHs in chronic toxicity to larval fish. [source] Behavioral effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatusENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2001Jing Ding Abstract Ivermectin is a potent antiparasitic drug against nematode and arthropod parasites. In this study, we examined the lethal and sublethal effects of ivermectin in a freshwater oligochaete, Lumbriculus variegatus. The median lethal concentration (LC50) at 72 h after ivermectin exposure was 560 nM. Sublethal endpoints focused on several stimulus-evoked locomotor behaviors: escape reflexes controlled by giant interneuron pathways, swimming and reversal, and crawling. Swimming, reversal, and crawling are controlled by nongiant interneuron pathways. Ivermectin inhibited swimming, reversal, crawling frequency, and crawling speed in a time- and concentration-dependent manner with a mean inhibitory concentration (IC50) at 3 h of 1.1, 16, 91, and 51nM, respectively. Ivermectin at 0.3 nM also significantly decreased the frequency of helical swimming waves. Picrotoxin, a Cl, channel blocker, antagonized the ivermectin-induced decrease in swimming frequency, crawling frequency, and crawling speed. There were no adverse effects on escape reflex 3 h after exposure to 300 nM ivermectin. Electrophysiological recordings showed that ivermectin had no effects on the conduction velocity of giant fiber systems. The results indicated that locomotor behaviors controlled by nongiant locomotor pathways were more sensitive to ivermectin than pathways controlled by giant interneurons and that Cl, channels may be involved in mediating ivermectin's inhibitory effects. [source] Developmental toxicity of estrogenic alkylphenols in killifish (Fundulus heteroclitus)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2000Sue A. Kelly Abstract Estrogenic alkylphenols have been identified in the aquatic environment, and concern has arisen over the ability of these compounds to interact with and potentially disrupt vertebrate endocrine systems. Here we report that waterborne nonylphenol (NP) and 4- tert -octylphenol (4- t -OP) are toxic to the embryos and larvae of Fundulus heteroclitus, an estuarine teleost, causing both lethal and sublethal developmental abnormalities. Hatch success in surviving embryos is also adversely affected by alkylphenol exposure. Correlation analysis has indicated that decreased hatch success is strongly correlated to deformities in the torso/abdomen and tail of embryos. Larval exposure to the alkylphenols demonstrates that NP and 4- t -OP are lethal at concentrations an order of magnitude less than those lethal to embryos (NP larval 96-h LC50 = 0.95 ,M [204 ,g/L]; NP embryo 96-h LC50 = 24 ,M [5 mg/L]). In evaluating the role of estrogenicity in developmental toxicity of the alkylphenols, we have found that tamoxifen, an estrogen receptor antagonist, can prevent embryo-lethality for NP and 4- t -OP While these embryos survive, some sublethal abnormalities are still evident, particularly in the torso and tail. The results of these studies suggest that the alkylphenols have the potential to cause developmental toxicity in aquatic organisms and that this may occur through disruption of estrogen-based signals. [source] Transformation of 2,4,6-trinitrotoluene in soil in the presence of the earthworm Eisenia andrei,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2000Agnès Y. Renoux Abstract The ability of the earthworm Eisenia andrei to metabolize 2,4,6-trinitrotoluene (TNT) was studied in experiments with TNT-spiked soils, dermal contact tests, and with an in vitro assay. Lethality of TNT in a forest sandy soil was first determined (14-d LC50 = 143 mg/kg). Then TNT at lethal and sublethal concentrations was applied to the same soil and was monitored along with its metabolites in extracts of soil and earthworm tissue for up to 14 d postapplication. High performance liquid chromatography-ultra violet analyses indicated that TNT was transformed in the presence of E. andrei by a reductive pathway to 2-amino-4,6-dinitrotoluene (2-ADNT), 4-amino-2,6-dinitrotoluene (4-ADNT), 2,4-diamino-6-nitrotoluene (2,4-DANT), and traces of 2,6-di-amino-4-nitrotoluene (2,6-DANT) in earthworm tissues. This transformation could be explained by either a metabolic mechanism within the earthworm or by the enhancement of an earthworm-associated microbial activity or both. The TNT concentrations decreased from the spiked soils. However, the monoamino-dinitrotoluene (2-ADNT and 4-ADNT) concentrations increased with exposure duration and were dependent on the initial TNT soil concentrations. This was also observed to a lesser extent in the TNT-spiked soils with no earthworms present. The biotransformation of TNT into 2-ADNT, 4-ADNT, and 2,4-DANT and the presence of these metabolites in E. andrei after dermal contact on TNT-spiked filter paper showed that dermal uptake can be a significant exposure route for TNT. In vitro experiments showed that earthworm homogenate could metabolize TNT and form 2-ADNT and 4-ADNT at room temperature and at 37°C. This effect was inhibited by heat inactivation prior to incubation or by incubation at 4°C, suggesting that the biotransformation of TNT in the presence of E. andrei may be enzymatic in nature. [source] PRECLINICAL STUDY: Mice lacking Gad2 show altered behavioral effects of ethanol, flurazepam and gabaxadolADDICTION BIOLOGY, Issue 1 2010Yuri A. Blednov ABSTRACT ,-Aminobutyric acid (GABA) is synthesized in brain by two isoforms of glutamic acid decarboxylase (Gad), Gad1 and Gad2. Gad1 provides most of the GABA in brain, but Gad2 can be rapidly activated in times of high GABA demand. Mice lacking Gad2 are viable whereas deletion of Gad1 is lethal. We produced null mutant mice for Gad2 on three different genetic backgrounds: predominantly C57BL/6J and one or two generations of backcrossing to 129S1/SvimJ (129N1, 129N2). We used these mice to determine if actions of alcohol are regulated by synthesis of GABA from this isoform. We also studied behavioral responses to a benzodiazepine (flurazepam) and a GABAA receptor agonist (gabaxadol). Deletion of Gad2 increased ethanol palatability and intake and slightly reduced the severity of ethanol-induced withdrawal, but these effects depended strongly on genetic background. Mutant mice on the 129N2 background showed the above three ethanol behavioral phenotypes, but the C57BL/6J inbred background did not show any of these phenotypes. Effects on ethanol consumption also depended on the test as the mutation did not alter consumption in limited access models. Deletion of Gad2 reduced the effect of flurazepam on motor incoordination and increased the effect of extrasynaptic GABAA receptor agonist gabaxadol without changing the duration of loss of righting reflex produced by these drugs. These results are consistent with earlier proposals that deletion of Gad2 (on 129N2 background) reduces synaptic GABA but also suggest changes in extrasynaptic receptor function. [source] PRECLINICAL STUDY: Mechanisms of respiratory insufficiency induced by methadone overdose in ratsADDICTION BIOLOGY, Issue 1 2010Lucie Chevillard ABSTRACT Methadone may cause respiratory depression. We aimed to understand methadone-related effects on ventilation as well as each opioid-receptor (OR) role. We studied the respiratory effects of intraperitoneal methadone at 1.5, 5, and 15 mg/kg (corresponding to 80% of the lethal dose-50%) in rats using arterial blood gases and plethysmography. OR antagonists, including intravenous 10 mg/kg-naloxonazine at 5 minutes (mu-OR antagonist), subcutaneous 30 mg/kg-naloxonazine at 24 hours (mu1-OR antagonist), 3 mg/kg-naltrindole at 45 minutes (delta-OR antagonist) and 5 mg/kg-Nor-binaltorphimine at 6 hours (kappa-OR antagonist) were pre-administered. Plasma concentrations of methadone enantiomers were measured using high-performance liquid chromatography coupled to mass-spectrometry. Methadone dose-dependent inspiratory time (TI) increase tended to be linear. Respiratory depression was observed only at 15 mg/kg and characterized by an increase in expiratory time (TE) resulting in hypoxemia and respiratory acidosis. Intravenous naloxonazine completely reversed all methadone-related effects on ventilation, while subcutaneous naloxonazine reduced its effects on pH (P < 0.05), PaCO2 (P < 0.01) and TE (P < 0.001) but only partially on TI (P < 0.001). Naltrindole reduced methadone-related effects on TE (P < 0.001). Nor-binaltorphimine increased methadone-related effects on pH and PaO2 (P < 0.05) Respiratory effects as a function of plasma R -methadone concentrations showed a decrease in PaO2 (EC50: 1.14 µg/ml) at lower concentrations than those necessary for PaCO2 increase (EC50: 3.35 µg/ml). Similarly, increased TI (EC50: 0.501 µg/ml) was obtained at lower concentrations than those for TE (EC50: 4.83 µg/ml). Methadone-induced hypoxemia is caused by mu-ORs and modulated by kappa-ORs. Additionally, methadone-induced increase in TE is caused by mu1- and delta-opioid receptors while increase in TI is caused by mu-ORs. [source] A role for synGAP in regulating neuronal apoptosisEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005Irene Knuesel Abstract The brain-specific Ras/Rap GTPase-activating protein synGAP is a major component of the postsynaptic density at glutamatergic synapses. It is a target for phosphorylation by Ca2+/calmodulin-dependent protein kinase II, which up-regulates its GTPase-activating activity. Thus, SynGAP may play an important role in coupling N -methyl- d -aspartate-type glutamate receptor activation to signaling pathways downstream of Ras or Rap. Homozygous deletion of synGAP is lethal within the first few days after birth. Therefore, to study the functions of synGAP, we used the cre/loxP recombination system to produce conditional mice mutants in which gradual loss of synGAP begins at ,,1 week, and usually becomes maximal by 3 weeks, after birth. The resulting phenotypes fall into two groups. In a small group, the level of synGAP protein is reduced to 20,25% of wild type, and they die at 2,3 weeks of age. In a larger group, the levels remain higher than ,,40% of wild type, and they survive and remain healthy. In all mutants, however, an abnormally high number of neurons in the hippocampus and cortex undergo apoptosis, as detected by caspase-3 activation. The effect is cell autonomous, occurring only in neuronal types in which the synGAP gene is eliminated. The level of caspase-3 activation in neurons correlates inversely with the level of synGAP protein measured at 2 and 8 weeks after birth, indicating that neuronal apoptosis is enhanced by reduction of synGAP. These data show that synGAP plays a role in regulation of the onset of apoptotic neuronal death. [source] An essential role for the H218/AGR16/Edg-5/LPB2 sphingosine 1-phosphate receptor in neuronal excitabilityEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2001A. John MacLennan Abstract A wealth of indirect data suggest that the H218/AGR16/Edg-5/LPB2 sphingosine 1-phosphate (S1P) receptor plays important roles in development. In vitro, it activates several forms of development-related signal transduction and regulates cellular proliferation, differentiation and survival. It is expressed during embryogenesis, and mutation of an H218 -like gene in zebrafish leads to profound defects in embryonic development. Nevertheless, the in vivo functions served by H218 signalling have not been directly investigated. We report here that mice in which the H218 gene has been disrupted are unexpectedly born with no apparent anatomical or physiological defects. In addition, no abnormalities were observed in general neurological development, peripheral axon growth or brain structure. However, between 3 and 7 weeks of age, H218,/, mice have seizures which are spontaneous, sporadic and occasionally lethal. Electroencephalographic abnormalities were identified both during and between the seizures. At a cellular level, whole-cell patch-clamp recordings revealed that the loss of H218 leads to a large increase in the excitability of neocortical pyramidal neurons. Therefore, H218 plays an essential, unanticipated and functionally important role in the proper development and/or mediation of neuronal excitability. [source] Major components of a sea urchin block to polyspermy are structurally and functionally conservedEVOLUTION AND DEVELOPMENT, Issue 3 2004Julian L. Wong Summary One sperm fusing with one egg is requisite for successful fertilization; additional sperm fusions are lethal to the embryo. Because sperm usually outnumber eggs, evolution has selected for mechanisms that prevent this polyspermy by immediately modifying the egg extracellular matrix. We focus here on the contribution of cortical granule contents in the sea urchin block to polyspermy to begin to understand how well this process is conserved. We identified each of the major constituents of the fertilization envelope in two species of seaurchins, Strongylocentrotus purpuratus and Lytechinus variegatus, that diverged 30 to 50 million years ago. Our results show that the five major structural components of the fertilization envelope, derived from the egg cortical granules, are semiconserved. Most of these orthologs share sequence identity and encode multiple low-density lipoprotein receptor type A repeats or CUB domains but at least two contain radically different carboxy-terminal repeats. Using a new association assay, we also show that these major structural components are functionally conserved during fertilization envelope construction. Thus, it seems that this population of female reproductive proteins has retained functional motifs while gaining significant sequence diversity,two opposing paths that may reflect cooperativity among the proteins that compose the fertilization envelope. [source] Paternal germline mosaicism in Herlitz junctional epidermolysis bullosaEXPERIMENTAL DERMATOLOGY, Issue 5 2002Peter B. Cserhalmi-Friedman Abstract: We studied a single patient with the lethal (Herlitz) type of junctional epidermolysis bullosa (H-JEB). Screening for mutations in the LAMB3 gene in the patient revealed the previously described hotspot mutation R635X and a novel one basepair deletion in exon 10. The single basepair deletion 1094delA could be detected in the clinically unaffected mother, while the nonsense mutation R635X could not be found in the peripheral blood DNA of either parent. After excluding non-paternity by microsatellite analysis using random markers on chromosomes 3, 8 and 18, we determined that the mutation R635X in the proband was most likely the result of a de novo event or alternatively, germline mosaicism. The parents requested prenatal diagnosis for a second pregnancy, and while the maternal mutation 1094delA could not be detected in DNA from the fetus, unexpectedly, the mutation R635X was present in the chorionic villus DNA. These findings were most consistent with paternal germline mosaicism for the recessive mutation R635X. The results have had a significant impact on the genetic counseling in this family. To our knowledge, this study represents the first documented case of germline mosaicism in junctional epidermolysis bullosa, and serves as a reminder that germline mosaicism should be considered in cases in which a ,new' mutation is found in the offspring of a clinically and/or genetically unaffected parent. [source] | |||||||||||||||||||||||||||||||||||||||||||