Biological responses in fish exposed to municipal wastewater treatment plant effluent in situ

Effluents from municipal wastewater treatment plants (MWTPs) are complex mixtures of chemicals including endocrine-disrupting compounds (EDCs) and 17α-ethynylestradiol (EE2). The objective of this study was to evaluate selected responses of two fish species, in two different years, exposed in situ to MWTP effluent. Biological markers of exposure (plasma vitellogenin (VTG) and antioxidant enzymes) were measured in two species of male fish, rainbow trout (Oncorhynchus mykiss) and fathead minnow (Pimephales promelas), caged at sites associated with wastewater outfall. The estrogenicity of the final effluent in 2010 was determined to be 17.0 + 0.4 ng/L estrogen equivalents (EEQ) and reduced to 7.5 + 2.9 ng/L EEQ after infrastructure upgrades. Pharmaceuticals and personal care products in the effluent and surface water in both years confirmed the exposures at each downstream site. Despite the presence of estrogenic compounds in the MWTP effluent, no effluent-caged male fish demonstrated plasma VTG induction. Minnows and trout that received an intraperitoneal injection of 5 mg/g EE2 showed VTG induction at both field sites. In 2012, the liver somatic index (LSI) of both species increased with exposure, as did changes in antioxidant enzymes, and reactive oxygen species (ROS) activity. Multiple biological mechanisms are modified by effluent exposure, and multiple endpoints are needed to assess risk.Standards Development Branch|| Ontario Ministry of the Environment and Climate Change (OMECC)||the Canadian Water Network||Natural Sciences and Engineering Research Council|| Canada Research Chairsto MRS|| OMECC Laboratory Services Branch||Trent University||University of Ottawa ||Environment and Climate Change Canad

Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration

With the advance in material science and the need to diversify market applications, silver nanoparticles (AgNPs) are modified by different surface coatings. However, how these surface modifications influence the effects of AgNPs on human health is still largely unknown. We have evaluated the uptake, toxicity and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of AgNPs depends on the intracellular localization that was highly dependent on the surface charge. BPEI AgNPs ( potential=+46.5mV) induced the highest cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the highest damage to the nucleus of liver cells in the exposed mice, which is associated with a high accumulation in liver tissues. The PEG AgNPs ( potential=-16.2mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 mu g/g), which suggest better biocompatibility compared to the other chemically modified AgNPs. Moreover, the adsorption ability with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal biological inertia and can effectively resist opsonization or non-specific binding to protein in mice. The overall results indicated that the biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI AgNPs>Citrate AgNPs=PVP AgNPs>PEG AgNPs. This toxicological data could be useful in supporting the development of safe AgNPs for consumer products and drug delivery applications

Differential Modulation of Beta-Adrenergic Receptor Signaling by Trace Amine-Associated Receptor 1 Agonists

Trace amine-associated receptors (TAAR) are rhodopsin-like G-protein-coupled receptors (GPCR). TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR), phenylethylamine (PEA), octopamine (OA), but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1) and 2 (ADRB2) have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR) octopamine (OAR), ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes

Strategic Orientation and Social Enterprise Performance

Even though previous research indicates that an organization’s pursuit of strategic orientation (SO) has positive effects on its performance, we have deepened and expanded our understanding of how this concept can also be applied to social enterprises (SEs). Using data collected from British and Japanese social enterprises, we examined the mediating roles of market effectiveness and consumer satisfaction in both the social and commercial domains with regard to SO effects on performance, as well as how performance in one aspect of practice positively moderates the impact of SO behavior in another. The results contribute to the development of a theory for understanding the concept of SO associated with social enterprise performance. More generally, this article contributes to the ongoing efforts to understand the strategic management aspect of social enterprises