We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine ...environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section “other invertebrates” review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large-scale and wide ranging negative biological and ecological impacts on a wide range of non-target invertebrates in terrestrial, aquatic, marine and benthic habitats.
Neonicotinoids currently dominate the insecticide market as seed treatments on Canada's major Prairie crops (e.g., canola). The potential impact to ecologically significant wetlands in this ...dominantly agro-environment has largely been overlooked while the distribution of use, incidence and level of contamination remains unreported. We modelled the spatial distribution of neonicotinoid use across the three Prairie Provinces in combination with temporal assessments of water and sediment concentrations in wetlands to measure four active ingredients (clothianidin, thiamethoxam, imidacloprid and acetamiprid). From 2009 to 2012, neonicotinoid use was increasing; by 2012, applications covered an estimated ∼11 million hectares (44% of Prairie cropland) with >216,000 kg of active ingredients. Thiamethoxam, followed by clothianidin, were the dominant seed treatments by mass and area. Areas of high neonicotinoid use were identified as high density canola or soybean production. Water sampled four times from 136 wetlands (spring, summer, fall 2012 and spring 2013) across four rural municipalities in Saskatchewan similarly revealed clothianidin and thiamethoxam in the majority of samples. In spring 2012 prior to seeding, 36% of wetlands contained at least one neonicotinoid. Detections increased to 62% in summer 2012, declined to 16% in fall, and increased to 91% the following spring 2013 after ice-off. Peak concentrations were recorded during summer 2012 for both thiamethoxam (range: <LOQ--1490 ng/L, canola) and clothianidin (range: <LOQ--3110 ng/L, canola). Sediment samples collected during the same period rarely (6%) contained neonicotinoid concentrations (which did not exceed 20 ng/L). Wetlands situated in barley, canola and oat fields consistently contained higher mean concentrations of neonicotinoids than in grasslands, but no individual crop singularly influenced overall detections or concentrations. Distribution maps indicate neonicotinoid use is increasing and becoming more widespread with concerns for environmental loading, while frequently detected neonicotinoid concentrations in Prairie wetlands suggest high persistence and transport into wetlands.
Neonicotinoids are neurotoxic insecticides widely used as seed treatments, but little is known of their effects on migrating birds that forage in agricultural areas. We tracked the migratory ...movements of imidacloprid-exposed songbirds at a landscape scale using a combination of experimental dosing and automated radio telemetry. Ingestion of field-realistic quantities of imidacloprid (1.2 or 3.9 milligrams per kilogram body mass) by white-crowned sparrows (
) during migratory stopover caused a rapid reduction in food consumption, mass, and fat and significantly affected their probability of departure. Birds in the high-dose treatment stayed a median of 3.5 days longer at the site of capture after exposure as compared with controls, likely to regain fuel stores or recover from intoxication. Migration delays can carry over to affect survival and reproduction; thus, these results confirm a link between sublethal pesticide exposure and adverse outcomes for migratory bird populations.
Neonicotinoids, broad-spectrum systemic insecticides, are the fastest growing class of insecticides worldwide and are now registered for use on hundreds of field crops in over 120 different ...countries. The environmental profile of this class of pesticides indicate that they are persistent, have high leaching and runoff potential, and are highly toxic to a wide range of invertebrates. Therefore, neonicotinoids represent a significant risk to surface waters and the diverse aquatic and terrestrial fauna that these ecosystems support. This review synthesizes the current state of knowledge on the reported concentrations of neonicotinoids in surface waters from 29 studies in 9 countries world-wide in tandem with published data on their acute and chronic toxicity to 49 species of aquatic insects and crustaceans spanning 12 invertebrate orders. Strong evidence exists that water-borne neonicotinoid exposures are frequent, long-term and at levels (geometric means=0.13μg/L (averages) and 0.63μg/L (maxima)) which commonly exceed several existing water quality guidelines. Imidacloprid is by far the most widely studied neonicotinoid (66% of the 214 toxicity tests reviewed) with differences in sensitivity among aquatic invertebrate species ranging several orders of magnitude; other neonicotinoids display analogous modes of action and similar toxicities, although comparative data are limited. Of the species evaluated, insects belonging to the orders Ephemeroptera, Trichoptera and Diptera appear to be the most sensitive, while those of Crustacea (although not universally so) are less sensitive. In particular, the standard test species Daphnia magna appears to be very tolerant, with 24–96hour LC50 values exceeding 100,000μg/L (geometric mean>44,000μg/L), which is at least 2–3 orders of magnitude higher than the geometric mean of all other invertebrate species tested. Overall, neonicotinoids can exert adverse effects on survival, growth, emergence, mobility, and behavior of many sensitive aquatic invertebrate taxa at concentrations at or below 1μg/L under acute exposure and 0.1μg/L for chronic exposure. Using probabilistic approaches (species sensitivity distributions), we recommend here that ecological thresholds for neonicotinoid water concentrations need to be below 0.2μg/L (short-term acute) or 0.035μg/L (long-term chronic) to avoid lasting effects on aquatic invertebrate communities. The application of safety factors may still be warranted considering potential issues of slow recovery, additive or synergistic effects and multiple stressors that can occur in the field. Our analysis revealed that 81% (22/27) and 74% (14/19) of global surface water studies reporting maximum and average individual neonicotinoid concentrations respectively, exceeded these thresholds of 0.2 and 0.035μg/L. Therefore, it appears that environmentally relevant concentrations of neonicotinoids in surface waters worldwide are well within the range where both short- and long-term impacts on aquatic invertebrate species are possible over broad spatial scales.
•Neonicotinoids in surface waters often exceed existing regulatory guidelines.•Environmental persistence indicates regulatory thresholds using acute toxicity tests may underestimate toxic potential.•Daphnia magna, industry standard, is at least1000 times less sensitive than mean of all other aquatic invertebrates.•Large differences in LEC50 values relate to sensitivity among species not potency among neonicotinoids.•Predict effects on communities at water concentrations ≥0.2 (max) or 0.035μg/L (avg)
Basement membranes are a dense, sheet-like form of extracellular matrix (ECM) that underlie epithelia and endothelia, and surround muscle, fat and Schwann cells. Basement membranes separate tissues ...and protect them from mechanical stress. Although traditionally thought of as a static support structure, a growing body of evidence suggests that dynamic basement membrane deposition and modification instructs coordinated cellular behaviors and acts mechanically to sculpt tissues. In this Commentary, we highlight recent studies that support the idea that far from being a passive matrix, basement membranes play formative roles in shaping tissues.
Large-scale use of the persistent and potent neonicotinoid and fipronil insecticides has raised concerns about risks to ecosystem functions provided by a wide range of species and environments ...affected by these insecticides. The concept of ecosystem services is widely used in decision making in the context of valuing the service potentials, benefits, and use values that well-functioning ecosystems provide to humans and the biosphere and, as an endpoint (value to be protected), in ecological risk assessment of chemicals. Neonicotinoid insecticides are frequently detected in soil and water and are also found in air, as dust particles during sowing of crops and aerosols during spraying. These environmental media provide essential resources to support biodiversity, but are known to be threatened by long-term or repeated contamination by neonicotinoids and fipronil. We review the state of knowledge regarding the potential impacts of these insecticides on ecosystem functioning and services provided by terrestrial and aquatic ecosystems including soil and freshwater functions, fisheries, biological pest control, and pollination services. Empirical studies examining the specific impacts of neonicotinoids and fipronil to ecosystem services have focused largely on the negative impacts to beneficial insect species (honeybees) and the impact on pollination service of food crops. However, here we document broader evidence of the effects on ecosystem functions regulating soil and water quality, pest control, pollination, ecosystem resilience, and community diversity. In particular, microbes, invertebrates, and fish play critical roles as decomposers, pollinators, consumers, and predators, which collectively maintain healthy communities and ecosystem integrity. Several examples in this review demonstrate evidence of the negative impacts of systemic insecticides on decomposition, nutrient cycling, soil respiration, and invertebrate populations valued by humans. Invertebrates, particularly earthworms that are important for soil processes, wild and domestic insect pollinators which are important for plant and crop production, and several freshwater taxa which are involved in aquatic nutrient cycling, were all found to be highly susceptible to lethal and sublethal effects of neonicotinoids and/or fipronil at environmentally relevant concentrations. By contrast, most microbes and fish do not appear to be as sensitive under normal exposure scenarios, though the effects on fish may be important in certain realms such as combined fish-rice farming systems and through food chain effects. We highlight the economic and cultural concerns around agriculture and aquaculture production and the role these insecticides may have in threatening food security. Overall, we recommend improved sustainable agricultural practices that restrict systemic insecticide use to maintain and support several ecosystem services that humans fundamentally depend on.
Birds that travel long distances between their wintering and breeding grounds may be particularly susceptible to neurotoxic insecticides, but the influence of insecticides on migration ability is ...poorly understood. Following acute exposure to two widely used agricultural insecticides, imidacloprid (neonicotinoid) and chlorpyrifos (organophosphate), we compared effects on body mass, migratory activity and orientation in a seed-eating bird, the white-crowned sparrow (Zonotrichia leucophrys). During spring migration, sparrows were captured, held and dosed by gavage daily for 3 days with either the vehicle control, low (10% LD50) or high (25% LD50) doses of imidacloprid or chlorpyrifos and tested in migratory orientation trials pre-exposure, post-exposure and during recovery. Control birds maintained body mass and a seasonally appropriate northward orientation throughout the experiment. Imidacloprid dosed birds exhibited significant declines in fat stores and body mass (mean loss: -17% low, -25% high dose) and failed to orient correctly. Chlorpyrifos had no overt effects on mass but significantly impaired orientation. These results suggest that wild songbirds consuming the equivalent of just four imidacloprid-treated canola seeds or eight chlorpyrifos granules per day over 3 days could suffer impaired condition, migration delays and improper migratory direction, which could lead to increased risk of mortality or lost breeding opportunity.
Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T cells to kill cancer. The success of CAR-T cell therapies highlights the promise of programmed immunity and suggests that ...applying CAR strategies to other immune cell lineages may be beneficial. Here, we engineered a family of Chimeric Antigen Receptors for Phagocytosis (CAR-Ps) that direct macrophages to engulf specific targets, including cancer cells. CAR-Ps consist of an extracellular antibody fragment, which can be modified to direct CAR-P activity towards specific antigens. By screening a panel of engulfment receptor intracellular domains, we found that the cytosolic domains from Megf10 and FcRɣ robustly triggered engulfment independently of their native extracellular domain. We show that CAR-Ps drive specific engulfment of antigen-coated synthetic particles and whole human cancer cells. Addition of a tandem PI3K recruitment domain increased cancer cell engulfment. Finally, we show that CAR-P expressing murine macrophages reduce cancer cell number in co-culture by over 40%.
The purpose of this paper is to review the types of models that are currently being used in the area of municipal waste management and to highlight some major shortcomings of these models. Most of ...the municipal waste models identified in the literature are decision support models and for the purposes of this research, are divided into three categories—those based on cost benefit analysis, those based on life cycle assessment and those based on multicriteria decision making. Shortcomings of current waste management models include that they are concerned with refinements of the evaluation steps (e.g. stage four of AHP or the improvement of weight allocations in ELECTRE) rather than addressing the decision making process itself. In addition, while many models recognise that for a waste management model to be sustainable, it must consider environmental, economic and social aspects, no model examined considered all three aspects together in the application of the model.
Overexpression of SPARC, a collagen-binding glycoprotein, is strongly associated with tumor invasion through extracellular matrix in many aggressive cancers. SPARC regulates numerous cellular ...processes including integrin-mediated cell adhesion, cell signaling pathways, and extracellular matrix assembly; however, the mechanism by which SPARC promotes cell invasion in vivo remains unclear. A main obstacle in understanding SPARC function has been the difficulty of visualizing and experimentally examining the dynamic interactions between invasive cells, extracellular matrix and SPARC in native tissue environments. Using the model of anchor cell invasion through the basement membrane (BM) extracellular matrix in Caenorhabditis elegans, we find that SPARC overexpression is highly pro-invasive and rescues BM transmigration in mutants with defects in diverse aspects of invasion, including cell polarity, invadopodia formation, and matrix metalloproteinase expression. By examining BM assembly, we find that overexpression of SPARC specifically decreases levels of BM type IV collagen, a crucial structural BM component. Reduction of type IV collagen mimicked SPARC overexpression and was sufficient to promote invasion. Tissue-specific overexpression and photobleaching experiments revealed that SPARC acts extracellularly to inhibit collagen incorporation into BM. By reducing endogenous SPARC, we also found that SPARC functions normally to traffic collagen from its site of synthesis to tissues that do not express collagen. We propose that a surplus of SPARC disrupts extracellular collagen trafficking and reduces BM collagen incorporation, thus weakening the BM barrier and dramatically enhancing its ability to be breached by invasive cells.
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