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

Water Demand Management in England and Wales: constructions of the domestic water-user

YesMeasures to manage demand include implicit and explicit messages about domestic water-users which have important potential impacts on their perceptions and practices. Drawing on recent literature, this paper identifies three different ¿dimensions¿ along which demand management measures¿ constructions of the water-user may vary: these relate to whether the water user is passive or active, whether they are motivated by individual or common needs, and whether they perceive water as a right or a commodity. Demand management measures currently used in England and Wales are then discussed and analysed. The paper concludes by highlighting the importance of communications associated with demand management, and in particular, notes the need to consider the cumulative impact of messages and their interactions with people¿s existing understandings

Integration for Sustainable Development: A Report for Practitioners

A report based on research undertaken for the Ashford’s Integrated Alternatives (AIA) Project, 2009-2011EPSRC - under the Ashford's Integrated Alternatives Projec

An in situ investigation of Si(x)Ge(1-x) chemical vapor deposition by differential reflectance

An investigation of the surface kinetic processes of low pressure chemical vapor deposition (LPCVD) of Si, Ge, and SixGe1-x was carried out using time-resolved differential reflectance measurements. The source gas (disilane, digermane, or mixtures of these two, diluted in a helium carrier) was delivered to a heated substrate by a fast-acting modulated molecular jet valve. Thin film growth was studied in the temperature range of 400- 500°C on Si and Ge (001) substrates. The kinetics of chemisorption and of by-product desorption were determined from the surface differential reflectance signal obtained using a p-polarized, high-stability HeNe probe laser. Both chemisorption and by-product desorption were found to obey first-order kinetics. Chemisorption of the parent molecules was found to be relatively efficient (~5%) and weakly temperature dependent. For pure Si and Ge, by-product desorption occurred through a single first-order reaction. The activation energy of this step, ~2.75 eV for Si and ~ 1.5-2.2 eV for Ge, suggests that for both surfaces the stable chemisorption by-product is the monohydride, which decomposes via the elimination of molecular hydrogen. Two first-order desorption steps were inferred for the SixGe1-x alloy surfaces. These reactions are believed to be H2 desorption from Si- like and Ge-like surface sites. However, the activation energy of the more rapid of these two steps actually decreases as the Si content of the film increases. In the earlier portion of this work, Ge on Si and Ge on Ge LPCVD experiments were performed in a high-vacuum growth chamber. Later, a UHV system was used for heteroepitaxial growth of Si, Ge, and SixGe1-x thin films on Si substrates. The composition, morphology, and epitaxial and crystalline quality of the films grown in the UHV system were examined by Rutherford backscattering spectroscopy, x-ray diffraction, Raman spectroscopy, ellipsometry, and atomic force microscopy. Generally, these films were of high crystalline quality and were very well aligned with the substrate. Preferential incorporation of digermane into the film produced an alloy composition that was Ge-rich relative to the gas composition. The primary accomplishment of this work is the demonstration that the active surface layer of the important SixGe1-x system can be monitored in situ by an optical probe under typical LPCVD conditions. The results that we have obtained to date indicate that the rate-limiting step in Si or Ge LPCVD obeys simple first-order kinetics. Two first-order desorption steps were inferred for SixGe1-x alloy surfaces, but further work is needed to understand fully the rate-limiting surface reaction in SixGe1-x LPCVD

Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice

Obesity is closely associated with the metabolic syndrome, a combination of disorders including insulin resistance, diabetes, dyslipidemia, and hypertension. A role for local glucocorticoid reamplification in obesity and the metabolic syndrome has been suggested. The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active cortisol from inactive 11-keto forms, and aP2-HSD1 mice with relative transgenic overexpression of this enzyme in fat cells develop visceral obesity with insulin resistance and dyslipidemia. Here we report that aP2-HSD1 mice also have high arterial blood pressure (BP). The mice have increased sensitivity to dietary salt and increased plasma levels of angiotensinogen, angiotensin II, and aldosterone. This hypertension is abolished by selective angiotensin II receptor AT-1 antagonist at a low dose that does not affect BP in non-Tg littermates. These findings suggest that activation of the circulating renin-angiotensin system (RAS) develops in aP2-HSD1 mice. The long-term hypertension is further reflected by an appreciable hypertrophy and hyperplasia of the distal tubule epithelium of the nephron, resembling salt-sensitive or angiotensin II–mediated hypertension. Taken together, our findings suggest that overexpression of 11β-HSD1 in fat is sufficient to cause salt-sensitive hypertension mediated by an activated RAS. The potential role of adipose 11β-HSD1 in mediating critical features of the metabolic syndrome extends beyond obesity and metabolic complications to include the most central cardiovascular feature of this disorder

Validation of the COVAS (Comorbidities, Obesity, Vitals, Age, Sex) Score as a Practical Tool for Assessing Need for Intensive Care Services in Suspected SARS-CoV2 Patients

Background and Hypothesis  Various scoring instruments have been proposed to risk-stratify patients with suspected COVID-19. Here we test prognostic system derived and tested in the Kaiser Permanente health system (the COVAS score).   Experimental Design and Methods  This was a primary analysis of the multicenter RECOVER registry, which includes patients tested for SARs-CoV-2 from 40 emergency departments around the US.  We extracted components of COVAS score with two modifications, and computed a modified COVAS score, and used that as the “test” to compute the area under the receiver operating characteristic curve (AUROC) to predict any initial intensive care unit (ICU) admission or transfer to ICU.   Results  For SARS-CoV-2 positive patients, for the prediction of ICU admission, the COVAS AUROC=0.74 (95% CI = 0.72 to 0.77), with overall mean = 7.4 (SD=4.7), and the mean for ICU admission was higher (10.1, SD=4.6) versus no ICU admission (6.8, SD=4.5), p<0.001 paired t-test. For SARS-CoV-2 negative patients, the COVAS score showed an AUROC= 0.70 (0.68-0.72) and the mean was 7.3, SD=4.2.   Potential Impact  The modified COVAS scoring system had modest overall discriminative value at predicting ICU admission, but was more accurate in SARS-CoV-2 positive patients, compared with SARs-CoV-2 negative suggesting the instrument is calibrated to predict ICU requirements in patients with suspected COVID-19, as opposed to functioning as a generic risk-stratification tool.  &nbsp

Complexity through combination: an account of knitwear design

Designers immerse themselves in environments rich in inspiration. Previous research has tended to neglect the vital role of sources of inspiration in triggering and guiding designers' activities. This paper reports research which investigates the gathering of inspiration sources and exploration of ideas and hence attempts to understand how inspiration is harnessed. We conducted a progressive series of empirical studies looking at knitwear design: in situ observation; semi-structured interviews; constrained design tasks; and computational modelling. The paper proposes simple general accounts of observed design behaviour and shows how a simple parts-and-relations account can explicate aspects of subtlety and complexity in design

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

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

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