The Effect of Natural Dissolved Organic Carbon on the Acute Toxicity of Copper to Larval Freshwater Mussels (\u3cem\u3eGlochidia\u3c/em\u3e)

The present study examined the effect of dissolved organic carbon (DOC), both added and inherent, on Cu toxicity in glochidia, the larvae of freshwater mussels. Using incremental additions of natural DOC concentrate and reconstituted water, a series of acute copper toxicity tests were conducted. An increase in DOC from 0.7 to 4.4 mg C/L resulted in a fourfold increase (36–150 μg Cu/L) in the 24-h median effective concentration (EC50) and a significant linear relationship (r2=0.98, p=0.0008) between the DOC concentration and the Cu EC50 of Lampsilis siliquoidea glochidia. The ameliorating effect of added DOC on Cu toxicity was confirmed using a second mussel species, the endangered (in Canada) Lampsilis fasciola. The effect of inherent (i.e., not added) DOC on Cu toxicity was also assessed in eight natural waters (DOC 5–15 mg C/L). These experiments revealed a significant relationship between the EC50 and the concentration of inherent DOC (r2=0.79, p=0.0031) with EC50s ranging from 27 to 111 μg Cu/L. These laboratory tests have demonstrated that DOC provides glochidia with significant protection from acute Cu toxicity. The potential risk that Cu poses to mussel populations was assessed by comparing Cu and DOC concentrations from significant mussel habitats in Ontario to the EC50s. Although overall mean Cu concentration in the mussel’s habitat was well below the acutely toxic level given the concentration of DOC, episodic Cu releases in low DOC waters may be a concern for the recovery of endangered freshwater mussels. The results are examined in the context of current Cu water quality regulations including the U.S. Environmental Protection Agency’s (U.S. EPA) biotic ligand model

Physiological Responses to Acute Silver Exposure in the Freshwater Crayfish (\u3cem\u3eCambarus diogenes diogenes\u3c/em\u3e)—A Model Invertebrate?

Adult crayfish (Cambarus diogenes diogenes) exposed to 8.41 ± 0.17 μg silver/L (19.4% as Ag+) in moderately hard freshwater under flow-through conditions for 96 h exhibited ionoregulatory disturbance, elevated metabolic ammonia (Tamm) production and substantial silver accumulation in the gills, hemolymph, and hepatopancreas. The ionoregulatory disturbance included both a generally reduced unidirectional Na1 influx and an increased unidirectional Na+ efflux, leading to a substantial net loss of Na+ from the silver-exposed crayfish. The Na+ uptake in silver-exposed crayfish differed overall from controls, while the increased Na+ efflux recovered to control values 48 h into the 96 h of exposure. The general inhibition of Na+ uptake could be explained by a reduced sodium/potassium-adenosine triphosphatase (Na/K-ATPase) activity in terminally obtained gill samples from the silver exposed crayfish. The silver-induced effect on Na+ uptake and loss translated to reduced hemolymph Na+ concentrations but not significantly reduced hemolymph Cl- concentrations. Hemolymph Tamm and Tamm efflux both increased in silver-exposed crayfish, indicating an increased metabolic Tamm production. The present study demonstrates that the toxic mechanism of waterborne silver exposure in freshwater crayfish resembles that of freshwater teleost fish. The crayfish might therefore be a useful model system for extending current environmental regulatory strategies, currently based on teleost fish, to invertebrates

Clinical Trials and Novel Pathogens: Lessons Learned from SARS

During the recent global outbreak of severe acute respiratory syndrome (SARS), thousands of patients received treatments of uncertain efficacy and known toxicity such as ribavirin and corticosteroids. Despite this, no controlled clinical trials assessing the efficacy of these agents were conducted. If a second global SARS outbreak occurred, clinicians would not have controlled data on which to base therapeutic decisions. We discuss the unique methodologic and logistical challenges faced by researchers who attempt to conduct controlled trials of therapeutic agents during an outbreak of a novel or unknown infectious pathogen. We draw upon our own experience in attempting to conduct a randomized controlled trial (trial) of ribavirin therapy for SARS and discuss the lessons learned. Strategies to facilitate future clinical trials during outbreaks of unknown or novel pathogens are also presented

South Africa - CGIAR Partnership Results in New Maize Varieties with 30 to 50 percent higher yields

TB

Arrive, survive and thrive: essential stages in the re-colonization and recovery of zooplankton in urban lakes in Sudbury, Canada

The recovery of lakes from severe, historical acid and metal pollution requires that colonists of extirpated species arrive, survive and subsequently thrive. We employed 40 year records from weekly to monthly crustacean zooplankton samples from Middle and Clearwater lakes near Sudbury, Canada, to identify the main mechanistic bottlenecks in this recovery process. While both lakes now have circum-neutral pH, acidity decreased more rapidly in Middle Lake because of past liming interventions, while Clearwater Lake, being larger and supporting more housing, likely receives more zooplankton colonists than Middle Lake. Community richness increased much faster in Middle Lake than in Clearwater Lake, at 1.6 vs 0.9 species decade-1, respectively. Richness has recovered in Middle Lake, when assessed against a target of 9-16 species collection-1 determined from regional reference lakes, but it has not yet recovered in Clearwater Lake. Species accumulation curves and a metric of annual persistence show that this difference is a product not of greater rates of species introduction into Middle Lake, but rather to their greater annual persistence once introduced. Greater annual persistence was associated with better habitat quality (i.e., lower acid and metal toxicity) in Middle Lake, particularly early in the record, and lower planktivore abundance, more recently. These results support a growing consensus that ecological recovery of zooplankton from acidification and metal pollution does not depend strongly on propagule introduction rates which are adequate, but rather on propagule persistence, in lake-rich, suburban landscapes such as those near Sudbury

A peroxisome proliferator-activated receptor-δ agonist provides neuroprotection in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease

Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.Peer reviewedPublisher PD

IFN-γ signaling, with the synergistic contribution of TNF-α, mediates cell specific microglial and astroglial activation in experimental models of Parkinson's disease

To through light on the mechanisms underlying the stimulation and persistence of glial cell activation in Parkinsonism, we investigate the function of IFN-γ and TNF-α in experimental models of Parkinson's disease and analyze their relation with local glial cell activation. It was found that IFN-γ and TNF-α remained higher over the years in the serum and CNS of chronic Parkinsonian macaques than in untreated animals, accompanied by sustained glial activation (microglia and astroglia) in the substantia nigra pars compacta. Importantly, Parkinsonian monkeys showed persistent and increasing levels of IFN-γR signaling in both microglial and astroglial cells. In addition, experiments performed in IFN-γ and TNF-α KO mice treated with MPTP revealed that, even before dopaminergic cell death can be observed, the presence of IFN-γ and TNF-α is crucial for microglial and astroglial activation, and, together, they have an important synergistic role. Both cytokines were necessary for the full level of activation to be attained in both microglial and astroglial cells. These results demonstrate that IFN-γ signaling, together with the contribution of TNF-α, have a critical and cell-specific role in stimulating and maintaining glial cell activation in Parkinsonism

Role of the IL-1 Pathway in Dopaminergic Neurodegeneration and Decreased Voluntary Movement

Interleukin-1 (IL-1), a proinflammatory cytokine synthesized and released by activated microglia, can cause dopaminergic neurodegeneration leading to Parkinsons disease (PD). However, it is uncertain whether IL-1 can act directly, or by exacerbating the harmful actions of other brain insults. To ascertain the role of the IL-1 pathway on dopaminergic neurodegeneration and motor skills during aging, we compared mice with impaired [caspase-1 knockout (casp1(-/-))] or overactivated IL-1 activity [IL-1 receptor antagonist knockout (IL-1ra(-/-))] to wild-type (wt) mice at young and middle age. Their motor skills were evaluated by the open-field and rotarod tests, and quantification of their dopamine neurons and activated microglia within the substantia nigra were performed by immunohistochemistry. IL-1ra(-/-) mice showed an age-related decline in motor skills, a reduced number of dopamine neurons, and an increase in activated microglia when compared to wt or casp1(-/-) mice. Casp1(-/-) mice had similar changes in motor skills and dopamine neurons, but fewer activated microglia cells than wt mice. Our results suggest that the overactivated IL-1 pathway occurring in IL-1ra(-/-) mice in the absence of inflammatory interventions (e.g., intracerebral injections performed in animal models of PD) increased activated microglia, decreased the number of dopaminergic neurons, and reduced their motor skills. Decreased IL-1 activity in casp1(-/-) mice did not yield clear protective effects when compared with wt mice. In summary, in the absence of overt brain insults, chronic activation of the IL-1 pathway may promote pathological aspects of PD per se, but its impairment does not appear to yield advantages over wt mice.Funding Agencies|John Curtin School of Medical Research, The Australian National University</p