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

The Anisotropic Distribution of Galactic Satellites

We present a study of the spatial distribution of subhalos in galactic dark matter halos using dissipationless cosmological simulations of the concordance LCDM model. We find that subhalos are distributed anisotropically and are preferentially located along the major axes of the triaxial mass distributions of their hosts. The Kolmogorov-Smirnov probability for drawing our simulated subhalo sample from an isotropic distribution is P_KS \simeq 1.5 \times 10^{-4}. An isotropic distribution of subhalos is thus not the correct null hypothesis for testing the CDM paradigm. The nearly planar distribution of observed Milky Way (MW) satellites is marginally consistent (probability \simeq 0.02) with being drawn randomly from the subhalo distribution in our simulations. Furthermore, if we select the subhalos likely to be luminous, we find a distribution that is consistent with the observed MW satellites. In fact, we show that subsamples of the subhalo population with a centrally-concentrated radial distribution, similar to that of the MW dwarfs, typically exhibit a comparable degree of planarity. We explore the origin of the observed subhalo anisotropy and conclude that it is likely due to (1) preferential accretion of subhalos along filaments, often closely aligned with the major axis of the host halo, and (2) evolution of satellite orbits within the prolate, triaxial potentials typical of CDM halos. Agreement between predictions and observations requires the major axis of the outer dark matter halo of the Milky Way to be nearly perpendicular to the disk. We discuss possible observational tests of such disk-halo alignment with current large galaxy surveys.Comment: 14 pages (including appendix), 9 figures. Accepted for Publication in ApJ. Minor changes to reflect referee's comment

Engaging Opportunities: Connecting young people with contemporary research and researchers

This is the final report for ‘Engaging Opportunities’, an RCUK-funded School-University Partnership between the Open University and the Denbigh Teaching School Alliance. Informed by action research, this four-year project was designed to create structured, strategic, sustainable and equitable mechanisms for effective school-university engagement with research. The report describes an evidence-based strategy designed to embed school-university engagement with research within the University’s strategic planning for research and the operational practices of researchers. Through the early stages of our partnership we noted a lack of suitable planning tools that work for researchers, teachers and students. We therefore introduced a flexible and adaptable framework of four types of activity—open lectures, open dialogues, open inquiry and open creativity—combined with an upstream approach to planning based on a set of six principles. A sub-set of these activities were evaluated through a combination of surveys, interviews and interventions. In conclusion, we argue that institutional and professional cultures can be resistant to the prospect of fully embedding school-university engagement with research in a structured, strategic and sustainable manner, and offer suggestions for how this context could and should be changed

High star formation rates as the origin of turbulence in early and modern disk galaxies

High spatial and spectral resolution observations of star formation and kinematics in early galaxies have shown that two-thirds are massive rotating disk galaxies with the remainder being less massive non-rotating objects. The line of sight averaged velocity dispersions are typically five times higher than in today's disk galaxies. This has suggested that gravitationally-unstable, gas-rich disks in the early Universe are fuelled by cold, dense accreting gas flowing along cosmic filaments and penetrating hot galactic gas halos. However these accreting flows have not been observed, and cosmic accretion cannot power the observed level of turbulence. Here we report on a new sample of rare high-velocity-dispersion disk galaxies we have discovered in the nearby Universe where cold accretion is unlikely to drive their high star-formation rates. We find that the velocity dispersion is most fundamentally correlated with their star-formation rates, and not their mass nor gas fraction, which leads to a new picture where star formation itself is the energetic driver of galaxy disk turbulence at all cosmic epochs.Comment: 9 pages, 2 figures, Supplimentary Info available at: http://pulsar.swin.edu.au/~agreen/nature/sigma_mean_arXiv.pdf. Accepted for publication in Natur

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

The SAMI Galaxy Survey : spatially resolving the main sequence of star formation

We present the ∼800 star formation rate maps for the Sydney-AAO Multi-object Integral field spectrograph (SAMI) Galaxy Survey based on H α emission maps, corrected for dust attenuation via the Balmer decrement, that are included in the SAMI Public Data Release 1. We mask out spaxels contaminated by non-stellar emission using the [O iii]/H β, [N ii]/H α, [S ii]/H α, and [O i]/H α line ratios. Using these maps, we examine the global and resolved star-forming main sequences of SAMI galaxies as a function of morphology, environmental density, and stellar mass. Galaxies further below the star-forming main sequence are more likely to have flatter star formation profiles. Early-type galaxies split into two populations with similar stellar masses and central stellar mass surface densities. The main-sequence population has centrally concentrated star formation similar to late-type galaxies, while galaxies >3σ below the main sequence show significantly reduced star formation most strikingly in the nuclear regions. The split populations support a two-step quenching mechanism, wherein halo mass first cuts off the gas supply and remaining gas continues to form stars until the local stellar mass surface density can stabilize the reduced remaining fuel against further star formation. Across all morphologies, galaxies in denser environments show a decreased specific star formation rate from the outside in, supporting an environmental cause for quenching, such as ram-pressure stripping or galaxy interactions.Publisher PDFPeer reviewe