Effect of acute copper sulfate exposure on olfactory responses to amino acids and pheromones in goldfish (Carassius auratus)

Exposure of olfactory epithelium to environmentally relevant concentrations of copper disrupts olfaction in fish. To examine the dynamics of recovery at both functional and morphological levels after acute copper exposure, unilateral exposure of goldfish olfactory epithelia to 100 μM CuSO4 (10 min) was followed by electro-olfactogram (EOG) recording and scanning electron microscopy. Sensitivity to amino acids (L-arginine and L-serine), generally considered food-related odorants, recovered most rapidly (three days), followed by that to catecholamines(3-O-methoxytyramine),bileacids(taurolithocholic acid) and the steroid pheromone, 17,20 -dihydroxy-4-pregnen- 3-one 20-sulfate, which took 28 days to reach full recovery. Sensitivity to the postovulatory pheromone prostaglandin F2R had not fully recovered even at 28 days. These changes in sensitivity were correlated with changes in the recovery of ciliated and microvillous receptor cell types. Microvillous cells appeared largely unaffected by CuSO4 treatment. Cilia in ciliated receptor neurones, however, appeared damaged one day post-treatment and were virtually absent after three days but had begun to recover after 14 days. Together, these results support the hypothesis that microvillous receptor neurones detect amino acids whereas ciliated receptor neurones were not functional and are responsible for detection of social stimuli (bile acidsandpheromones).Furthermore, differences in sensitivity to copper may be due to different transduction pathways in the different cell types

Energy and flux variations across thin auroral arcs

Two discrete auroral arc filaments, with widths of less than 1 km, have been analysed using multi-station, multi-monochromatic optical observations from small and medium field-of-view imagers and the EISCAT radar. The energy and flux of the precipitating electrons, volume emission rates and local electric fields in the ionosphere have been determined at high temporal (up to 30 Hz) and spatial (down to tens of metres) resolution. A new time-dependent inversion model is used to derive energy spectra from EISCAT electron density profiles. The energy and flux are also derived independently from optical emissions combined with ion-chemistry modelling, and a good agreement is found. A robust method to obtain detailed 2-D maps of the average energy and number flux of small scale aurora is presented. The arcs are stretched in the north-south direction, and the lowest energies are found on the western, leading edges of the arcs. The large ionospheric electric fields (250 mV m?1) found from tristatic radar measurements are evidence of strong currents associated with the region close to the optical arcs. The different data sets indicate that the arcs appear on the boundaries between regions with different average energy of diffuse precipitation, caused by pitch-angle scattering. The two thin arcs on these boundaries are found to be related to an increase in number flux (and thus increased energy flux) without an increase in energ

Time Trends in Deaths Before Age 50 Years in People with Type 1 Diabetes:a nationwide analysis from Scotland 2004–2017

Acknowledgements We thank the SDRN Epidemiology Group: J. Chalmers (Diabetes Centre, Victoria Hospital, Kirkcaldy, UK), C. Fischbacher (Information Services Division, NHS National Services Scotland, Edinburgh, UK), B. Kennon (Queen Elizabeth University Hospital, Glasgow, UK), G. Leese (Ninewells Hospital, Dundee, UK), R. Lindsay (British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK), J. McKnight (Western General Hospital, NHS, UK), J. Petrie (Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK), R. McCrimmon (Division of Molecular and Clinical Medicine, University of Dundee, Dundee, UK), S. Philip (Grampian Diabetes Research Unit, Diabetes Centre, Aberdeen Royal Infirmary, Aberdeen, UK), D. McAllister (Institute of Health & Wellbeing, University of Glasgow, Glasgow, UK), E. Pearson (Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK) and S. Wild (Usher Institute, University of Edinburgh, Edinburgh, UK). The SDRN Epidemiology Group resource was originally set up under Ethics ref. 11/AL/0225, PAC 33/11 now running under PBPP ref. 1617-0147. Funding This study was supported by funding from Diabetes UK (17/0005627).Peer reviewedPublisher PD

Enabling the classroom and the curriculum: higher education, literary studies and disability

In this article the tripartite model of disability is applied to the lived experience of twenty-first-century higher education. The tripartite model facilitates a complex understanding of disability that recognises assumptions and discrimination but not at the cost of valued identity. This being so, not only the normative positivisms and non-normative negativisms but also the non-normative positivisms of the classroom and the curriculum are explored. Inclusion is taken as the starting point and the argument progresses to a profound and innovational appreciation of disability. The problem addressed is that inclusion, as shown in The Biopolitics of Disability, constitutes little more than inclusion-ism until disability is recognised in the context of alternative lives and values that neither enforce nor reify normalcy. Informed by this understanding, the article adopts the disciplinary example of literary studies and refers to Brian Friel’s Molly Sweeney as a primary text. The conclusion is that, despite passive and active resistance, disability enters higher education in many ways, most of which are beneficial to students and educators alike

MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis

MerTK, a receptor tyrosine kinase (RTK) of the TYRO3/AXL/MerTK family, is expressed in myeloid lineage cells in which it acts to suppress proinflammatory cytokines following ingestion of apoptotic material. Using syngeneic mouse models of breast cancer, melanoma, and colon cancer, we found that tumors grew slowly and were poorly metastatic in MerTK–/– mice. Transplantation of MerTK–/– bone marrow, but not wild-type bone marrow, into lethally irradiated MMTV-PyVmT mice (a model of metastatic breast cancer) decreased tumor growth and altered cytokine production by tumor CD11b+ cells. Although MerTK expression was not required for tumor infiltration by leukocytes, MerTK–/– leukocytes exhibited lower tumor cell–induced expression of wound healing cytokines, e.g., IL-10 and growth arrest-specific 6 (GAS6), and enhanced expression of acute inflammatory cytokines, e.g., IL-12 and IL-6. Intratumoral CD8+ T lymphocyte numbers were higher and lymphocyte proliferation was increased in tumor-bearing MerTK–/– mice compared with tumor-bearing wild-type mice. Antibody-mediated CD8+ T lymphocyte depletion restored tumor growth in MerTK–/– mice. These data demonstrate that MerTK signaling in tumor-associated CD11b+ leukocytes promotes tumor growth by dampening acute inflammatory cytokines while inducing wound healing cytokines. These results suggest that inhibition of MerTK in the tumor microenvironment may have clinical benefit, stimulating antitumor immune responses or enhancing immunotherapeutic strategies