Chronic exposure to neonicotinoids increases neuronal vulnerability to mitochondrial dysfunction in the bumblebee (Bombus terrestris)

This work was funded jointly by the Biotechnology and Biological Sciences Research Council, the Department for Environment, Food and Rural Affairs, the Natural Environment Research Council, the Scottish Government, and The Wellcome Trust, under the Insect Pollinators Initiative (United Kingdom) Grant BB/ 1000313/1 (to C.N.C.).The global decline in the abundance and diversity of insect pollinators could result from habitat loss, disease, and pesticide exposure. The contribution of the neonicotinoid insecticides (e.g., clothianidin and imidacloprid) to this decline is controversial, and key to understanding their risk is whether the astonishingly low levels found in the nectar and pollen of plants is sufficient to deliver neuroactive levels to their site of action: the bee brain. Here we show that bumblebees (Bombusterrestris audax) fed field levels [10 nM, 2.1 ppb (w/w)] of neonicotinoid accumulate between 4 and 10 nM in their brains within 3 days. Acute (minutes) exposure of cultured neurons to 10 nM clothianidin, but not imidacloprid, causes a nicotinic acetylcholine receptor-dependent rapid mitochondrial depolarization. However, a chronic (2 days) exposure to 1 nM imidacloprid leads to a receptor-dependent increased sensitivity to a normally innocuous level of acetylcholine, which now also causes rapid mitochondrial depolarization in neurons. Finally, colonies exposed to this level of imidacloprid show deficits in colony growth and nest condition compared with untreated colonies. These findings provide a mechanistic explanation for the poor navigation and foraging observed in neonicotinoid treated bumblebee colonies.Publisher PDFPeer reviewe

Cholinergic pesticides cause mushroom body neuronal inactivation in honeybees

Pesticides that target cholinergic neurotransmission are highly effective, but their use has been implicated in insect pollinator population decline. Honeybees are exposed to two widely used classes of cholinergic pesticide: neonicotinoids (nicotinic receptor agonists) and orga-nophosphate miticides (acetylcholinesterase inhibitors). Although sublethal levels of neoni-cotinoids are known to disrupt honeybee learning and behaviour, the neurophysiological basis of these effects has not been shown. Here, using recordings from mushroom body Kenyon cells in acutely isolated honeybee brain, we show that the neonicotinoids imidacloprid and clothianidin, and the organophosphate miticide coumaphos oxon, cause a depolarization-block of neuronal firing and inhibit nicotinic responses. These effects are observed at concentrations that are encountered by foraging honeybees and within the hive, and are additive with combined application. Our findings demonstrate a neuronal mechanism that may account for the cognitive impairments caused by neonicotinoids, and predict that exposure to multiple pesticides that target cholinergic signalling will cause enhanced toxicity to pollinators

Exposure to acetylcholinesterase inhibitors alters the physiology and motor function of honeybees

Cholinergic signalling is fundamental to neuro-muscular function in most organisms. Sub-lethal doses of neurotoxic pesticides that target cholinergic signalling can alter the behaviour of insects in subtle ways; their influence on non-target organisms may not be readily apparent in simple mortality studies. Beneficial arthropods such as honeybees perform sophisticated behavioural sequences during foraging that, if influenced by pesticides, could impair foraging success and reduce colony health. Here, we investigate the behavioural effects on honeybees of exposure to a selection of pesticides that target cholinergic signalling by inhibiting acetylcholinesterase (AChE). To examine how continued exposure to AChE inhibitors affected motor function, we fed adult foraging worker honeybees sub-lethal concentrations of these compounds in sucrose solution for 24 h. Using an assay for locomotion in bees, we scored walking, stopped, grooming, and upside down behaviour continuously for 15 min. At a 10nM concentration, all the AChE inhibitors caused similar effects on behaviour, notably increased grooming activity and changes in the frequency of bouts of behaviour such as head grooming. Coumaphos caused dose-dependent effects on locomotion as well as grooming behaviour, and a 1µM concentration of coumaphos induced symptoms of malaise such as abdomen grooming and defecation. Biochemical assays confirmed that the 4 compounds we assayed (coumaphos, aldicarb, chlorpyrifos, and donepezil) or their metabolites acted as AChE inhibitors in bees. Furthermore, we show that transcript expression levels of two honeybee acetylcholinesterase inhibitors were selectively upregulated in the brain and in gut tissues in response to AChE inhibitor exposure. The results of our study imply that the effects of pesticides that rely on this mode of action have subtle yet profound effects on physiological effects on behaviour that could lead to reduced survival

5-hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT₃ receptor resensitization due to Its subsequent release

The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT(3)) receptors. We report that recombinantly expressed 5-HT(3) receptor binding sites are reduced by chronic exposure to 5-HT (IC(50) of 154.0 ± 45.7 μm, t(½) = 28.6 min). This is confirmed for 5-HT(3) receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC(50) of 2.3 ± 1.0 μm, t(½) = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization

Environmental pharmacology—Dosing the environment: IUPHAR review 36

Pesticide action is predominantly measured as a toxicological outcome, with pharmacological impact of sublethal doses on bystander species left largely undocumented. Likewise, chronic exposure, which often results in responses different from acute administration, has also been understudied. In this article, we propose the application of standard pharmacological principles, already used to establish safe clinical dosing regimens in humans, to the ‘dosing of the environment’. These principles include relating the steady state dose of an agent to its beneficial effects (e.g. pest control), while minimising harmful impacts (e.g. off‐target bioactivity in beneficial insects). We propose the term ‘environmental therapeutic window’, analogous to that used in mammalian pharmacology, to guide risk assessment. To make pharmacological terms practically useful to environmental protection, quantitative data on pesticide action need to be made available in a freely accessible database, which should include toxicological and pharmacological impacts on both target and off‐target species

The DEEP2 Galaxy Redshift Survey: Spectral classification of galaxies at z~1

We present a Principal Component Analysis (PCA)-based spectral classification, eta, for the first 5600 galaxies observed in the DEEP2 Redshift Survey. This parameter provides a very pronounced separation between absorption and emission dominated galaxy spectra - corresponding to passively evolving and actively star-forming galaxies in the survey respectively. In addition it is shown that despite the high resolution of the observed spectra, this parameter alone can be used to quite accurately reconstruct any given galaxy spectrum, suggesting there are not many `degrees of freedom' in the observed spectra of this galaxy population. It is argued that this form of classification, eta, will be particularly valuable in making future comparisons between high and low-redshift galaxy surveys for which very large spectroscopic samples are now readily available, particularly when used in conjunction with high-resolution spectral synthesis models which will be made public in the near future. We also discuss the relative advantages of this approach to distant galaxy classification compared to other methods such as colors and morphologies. Finally, we compare the classification derived here with that adopted for the 2dF Galaxy Redshift Survey and in so doing show that the two systems are very similar. This will be particularly useful in subsequent analyses when making comparisons between results from each of these surveys to study evolution in the galaxy populations and large-scale structure.Comment: 10 pages, 9 figures, Accepted for publication in Ap

Tracing the Filamentary Structure of the Galaxy Distribution at z~0.8

We study filamentary structure in the galaxy distribution at z ~ 0.8 using data from the Deep Extragalactic Evolutionary Probe 2 (DEEP2) Redshift Survey and its evolution to z ~ 0.1 using data from the Sloan Digital Sky Survey (SDSS). We trace individual filaments for both surveys using the Smoothed Hessian Major Axis Filament Finder, an algorithm which employs the Hessian matrix of the galaxy density field to trace the filamentary structures in the distribution of galaxies. We extract 33 subsamples from the SDSS data with a geometry similar to that of DEEP2. We find that the filament length distribution has not significantly changed since z ~ 0.8, as predicted in a previous study using a \LamdaCDM cosmological N-body simulation. However, the filament width distribution, which is sensitive to the non-linear growth of structure, broadens and shifts to smaller widths for smoothing length scales of 5-10 Mpc/h from z ~ 0.8 to z ~ 0.1, in accord with N-body simulations.Comment: 10 pages, 8 figures, accepted for the publication in MNRA

Observations of ice multiplication in a weakly convective cell embedded in supercooled mid-level stratus

Simultaneous observations of cloud microphysical properties were obtained by in-situ aircraft measurements and ground based Radar/Lidar. Widespread mid-level stratus cloud was present below a temperature inversion (~5 °C magnitude) at 3.6 km altitude. Localised convection (peak updraft 1.5 m s−1) was observed 20 km west of the Radar station. This was associated with convergence at 2.5 km altitude. The convection was unable to penetrate the inversion capping the mid-level stratus. The mid-level stratus cloud was vertically thin (~400 m), horizontally extensive (covering 100 s of km) and persisted for more than 24 h. The cloud consisted of supercooled water droplets and small concentrations of large (~1 mm) stellar/plate like ice which slowly precipitated out. This ice was nucleated at temperatures greater than −12.2 °C and less than −10.0 °C, (cloud top and cloud base temperatures, respectively). No ice seeding from above the cloud layer was observed. This ice was formed by primary nucleation, either through the entrainment of efficient ice nuclei from above/below cloud, or by the slow stochastic activation of immersion freezing ice nuclei contained within the supercooled drops. Above cloud top significant concentrations of sub-micron aerosol were observed and consisted of a mixture of sulphate and carbonaceous material, a potential source of ice nuclei. Particle number concentrations (in the size range 0.1<D<3.0 μm) were measured above and below cloud in concentrations of ~25 cm−3. Ice crystal concentrations in the cloud were constant at around 0.2 L−1. It is estimated that entrainment of aerosol particles into cloud cannot replenish the loss of ice nuclei from the cloud layer via precipitation. Precipitation from the mid-level stratus evaporated before reaching the surface, whereas rates of up to 1 mm h−1 were observed below the convective feature. There is strong evidence for the Hallett-Mossop (HM) process of secondary ice particle production leading to the formation of the precipitation observed. This includes (1) Ice concentrations in the convective feature were more than an order of magnitude greater than the concentration of primary ice in the overlaying stratus, (2) Large concentrations of small pristine columns were observed at the ~−5 °C level together with liquid water droplets and a few rimed ice particles, (3) Columns were larger and increasingly rimed at colder temperatures. Calculated ice splinter production rates are consistent with observed concentrations if the condition that only droplets greater than 24 μm are capable of generating secondary ice splinters is relaxed. This case demonstrates the importance of understanding the formation of ice at slightly supercooled temperatures, as it can lead to secondary ice production and the formation of precipitation in clouds which may not otherwise be considered as significant precipitation sources

QRIS: A Quantitative Reflectance Imaging System for the Pristine Sample of Asteroid Bennu

The Quantitative Reflectance Imaging System (QRIS) is a laboratory-based spectral imaging system constructed to image the sample of asteroid Bennu delivered to Earth by the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) spacecraft. The system was installed in the OSIRIS-REx cleanroom at NASA's Johnson Space Center to collect data during preliminary examination of the Bennu sample. QRIS uses a 12-bit machine vision camera to measure reflectance over wavelength bands spanning the near ultraviolet to the near infrared. Raw data are processed by a calibration pipeline that generates a series of monochromatic, high-dynamic-range reflectance images, as well as band ratio maps, band depth maps, and 3-channel color images. The purpose of these spectral reflectance data is to help characterize lithologies in the sample and compare them to lithologies observed on Bennu by the OSIRIS-REx spacecraft. This initial assessment of lithological diversity was intended to help select the subsamples that will be used to address mission science questions about the early solar system and the origins of life and to provide important context for the selection of representative subsamples for preservation and distribution to international partners. When QRIS imaged the Bennu sample, unexpected calibration issues arose that had not been evident at imaging rehearsals and negatively impacted the quality of QRIS data. These issues were caused by stray light within the lens and reflections off the glovebox window and interior, and were exacerbated by the sample's extremely low reflectance. QRIS data were useful for confirming conclusions drawn from other data, but reflectance and spectral data from QRIS alone unfortunately have limited utility.Comment: 41 pages, 27 figure