Predictable hydrodynamic conditions explain temporal variations in the density of benthic foraging seabirds in a tidal stream environment

VC International Council for the Exploration of the Sea 2016. James J. Waggitt was funded by a NERC Case studentship supported by OpenHydro Ltd and Marine Scotland Science (NE/J500148/1). Shore-based surveys were funded by a NERC (NE/J004340/1) and a Scottish National Heritage (SNH) grant. FVCOM was funded by a NERC grant (NE/J004316/1). The bathymetry data used in hydrodynamic models (HI 1122 Sanday Sound to Westray Firth) was collected by the Maritime and Coastguard Agency (MCA) as part of the UK Civil Hydrography Programme. We wish to thank Christina Bristow, Matthew Finn and Jennifer Norris at the European Marine Energy Centre (EMEC); Ian Davies at Marine Scotland Science; Gail Davoren, Shaun Fraser, Pauline Goulet, Alex Robbins and Helen Wade for invaluable discussions; Thomas Cornulier, Alex Douglas, James Grecian and Samantha Patrick for their help with statistical analysis; and Jenny Campbell and the Cockram family for assistance during fieldwork.Peer reviewedPublisher PD

The Mathematical Game

Monte Carlo Tree Search can be used for automated theorem proving. Holophrasm is a neural theorem prover using MCTS combined with neural networks for the policy and the evaluation. In this paper we propose to improve the performance of the Holophrasm theorem prover using other game tree search algorithms

An early burst of IFN-γ induced by the pre-erythrocytic stage favours Plasmodium yoelii parasitaemia in B6 mice

<p>Abstract</p> <p>Background</p> <p>In murine models of malaria, an early proinflammatory response has been associated with the resolution of blood-stage infection. To dissect the protective immune mechanims that allow the control of parasitaemia, the early immune response of C57BL/6 mice induced during a non-lethal plasmodial infection was analysed.</p> <p>Methods</p> <p>Mice were infected with <it>Plasmodium yoelii </it>265BY sporozoites, the natural invasive form of the parasite, in order to complete its full life cycle. The concentrations of three proinflammatory cytokines in the sera of mice were determined by ELISA at different time points of infection. The contribution of the liver and the spleen to this cytokinic response was evaluated and the cytokine-producing lymphocytes were identified by flow cytometry. The physiological relevance of these results was tested by monitoring parasitaemia in genetically deficient C57BL/6 mice or wild-type mice treated with anti-cytokine neutralizing antibody. Finally, the cytokinic response in sera of mice infected with parasitized-RBCs was analysed.</p> <p>Results</p> <p>The early immune response of C57BL/6 mice to sporozoite-induced malaria is characterized by a peak of IFN-γ in the serum at day 5 of infection and splenic CD4 T lymphocytes are the major producer of this cytokine at this time point. Somewhat unexpected, the parasitaemia is significantly lower in <it>P. yoelii</it>-infected mice in the absence of IFN-γ. More precisely, at early time points of infection, IFN-γ favours parasitaemia, whereas helping to clear efficiently the blood-stage parasites at later time points. Interestingly, the early IFN-γ burst is induced by the pre-erythrocytic stage.</p> <p>Conclusion</p> <p>These results challenge the current view regarding the role of IFN-γ on the control of parasite growth since they show that IFN-γ is not an essential mediator of protection in <it>P. yoelii</it>-infected C57BL/6 mice. Moreover, the mice parasitaemia is more efficiently controlled in the absence of an early IFN-γ production, suggesting that this cytokine promotes parasite's growth. Finally, this early burst of IFN-γ is induced by the pre-erythrocytic stage, showing the impact of this stage on the immune response taking place during the subsequent erythrocytic stage.</p

Quantifying pursuit-diving seabirds’ associations with fine-scale physical features in tidal stream environments

Acknowledgements: James J. Waggitt was funded by a NERC Case studentship supported by OpenHydro Ltd and Marine Scotland Science (NE/J500148/1). Vessel-based transects were funded by a NERC (NE/J004340/1) and a Scottish National Heritage (SNH) grant. FVCOM modelling was funded by a NERC grant (NE/J004316/1). Marine Scotland Science provided time on the FRV Alba-na-Mara as part as the Marine Collaboration Research Forum (MarCRF). The bathymetry data used in hydrodynamic models (HI 1122 Sanday Sound to Westray Firth) was collected by the Maritime & Coastguard Agency (MCA) as part of the UK Civil Hydrography Programme. We wish to thank Christina Bristow, Matthew Finn and Jennifer Norris at the European Marine Energy Centre (EMEC); Marianna Chimienti, Ciaran Cronin, Tim Sykes and Stuart Thomas for performing vessel-based transects; Marine Scotland Science staff Eric Armstrong, Ian Davies, Mike Robertson, Robert Watret and Michael Stewart for their assistance; Shaun Fraser, Pauline Goulet, Alex Robbins, Helen Wade and Jared Wilson for invaluable discussions; Thomas Cornulier, Alex Douglas, James Grecian and Samantha Patrick for their help with statistical analysis; and Gavin Siriwardena, Leigh Torres, Mark Whittingham and Russell Wynn for their constructive comments on earlier versions of this manuscript. APC paid through institutional prepayment schemePeer reviewedPublisher PD

Maturation of the GABAergic Transmission in Normal and Pathologic Motoneurons

γ-aminobutyric acid (GABA) acting on Cl−-permeable ionotropic type A (GABAA) receptors (GABAAR) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates. In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the construction of neural networks but GABA also acts as a potent trophic factor. In the present paper, we concentrate on brainstem and spinal motoneurons that are largely targeted by GABAergic interneurons, and we bring together data on the switch from excitatory to inhibitory effects of GABA, on the maturation of the GABAergic system and GABAAR subunits. We finally discuss the role of GABA and its GABAAR in immature hypoglossal motoneurons of the spastic (SPA) mouse, a model of human hyperekplexic syndrome

Multifaceted Role of Heme during Severe Plasmodium falciparum Infections in India

Several immunomodulatory factors are involved in malaria pathogenesis. Among them, heme has been shown to play a role in the pathophysiology of severe malaria in rodents, but its role in human severe malaria remains unclear. Circulating levels of total heme and its main scavenger, hemopexin, along with cytokine/chemokine levels and biological parameters, including hemoglobin and creatinine levels, as well as transaminase activities, were measured in the plasma of 237 Plasmodium falciparum-infected patients living in the state of Odisha, India, where malaria is endemic. All patients were categorized into well-defined groups of mild malaria, cerebral malaria (CM), or severe noncerebral malaria, which included acute renal failure (ARF) and hepatopathy. Our results show a significant increase in total plasma heme levels with malaria severity, especially for CM and malarial ARF. Spearman rank correlation and canonical correlation analyses have shown a correlation between total heme, hemopexin, interleukin-10, tumor necrosis factor alpha, gamma interferon-induced protein 10 (IP-10), and monocyte chemotactic protein 1 (MCP-1) levels. In addition, canonical correlations revealed that heme, along with IP-10, was associated with the CM pathophysiology, whereas both IP-10 and MCP-1 together with heme discriminated ARF. Altogether, our data indicate that heme, in association with cytokines and chemokines, is involved in the pathophysiology of both CM and ARF but through different mechanisms.Indo-French Centre for the Promotion of Advanced Research, Associated International Laboratory Systems (LIA; CNRS), Immunology and Genetics of Infectious Diseases (SIGID), Department of Biotechnology from the Ministry of Science and Technology of India (DBT), Tata Institute of Fundamental Research (TIFR) (intramural funds), Université Lille (doctoral contract), IFCPAR (Raman-Charpak award), College Doctoral Lille Nord de France (AAP n10 award), Fondation des Treille, Conseil Régional du Nord-Pas de Calais

Constitutive Endocytosis and Degradation of the Pre-T Cell Receptor

The pre-T cell receptor (TCR) signals constitutively in the absence of putative ligands on thymic stroma and signal transduction correlates with translocation of the pre-TCR into glycolipid-enriched microdomains (rafts) in the plasma membrane. Here, we show that the pre-TCR is constitutively routed to lysosomes after reaching the cell surface. The cell-autonomous down-regulation of the pre-TCR requires activation of the src-like kinase p56lck, actin polymerization, and dynamin. Constitutive signaling and degradation represents a feature of the pre-TCR because the γδTCR expressed in the same cell line does not exhibit these features. This is also evident by the observation that the protein adaptor/ubiquitin ligase c-Cbl is phosphorylated and selectively translocated into rafts in pre-TCR– but not γδTCR-expressing cells. A role of c-Cbl–mediated ubiquitination in pre-TCR degradation is supported by the reduction of degradation through pharmacological inhibition of the proteasome and through a dominant-negative c-Cbl ubiquitin ligase as well as by increased pre-TCR surface expression on immature thymocytes in c-Cbl–deficient mice. The pre-TCR internalization contributes significantly to the low surface level of the receptor on developing T cells, and may in fact be a requirement for optimal pre-TCR function

A new ELISA kit which uses a combination of Plasmodium falciparum extract and recombinant Plasmodium vivax antigens as an alternative to IFAT for detection of malaria antibodies

BACKGROUND: The methods most commonly used to measure malarial antibody titres are the Indirect Fluorescence Antibody Test (IFAT), regarded as the gold standard, and the Enzyme-Linked ImmunoSorbent Assay (ELISA). The objective here was to assess the diagnostic performance, i.e. the sensitivity and specificity, of a new malaria antibody ELISA kit in comparison to IFAT. This new ELISA kit, the ELISA malaria antibody test (DiaMed), uses a combination of crude soluble Plasmodium falciparum extract and recombinant Plasmodium vivax antigens. METHODS: Two groups were used: 95 samples from malaria patients to assess the clinical sensitivity and 2,152 samples from blood donors, who had not been exposed to malaria, to assess the clinical specificity. RESULTS: The DiaMed ELISA test kit had a clinical sensitivity of 84.2% and a clinical specificity of 99.6% as compared with 70.5% and 99.6% respectively, using the IFAT method. The ELISA method was more sensitive than the IFAT method for P. vivax infections (75% vs. 25%). However, in 923 malaria risk donors the analytical sensitivity of the ELISA test was 40% and its specificity 98.3%, performances impaired by large numbers of equivocal results non-concordant between ELISA and IFAT. When the overall analytical performances of ELISA was compared to IFAT, the ELISA efficiency J index was 0.84 versus 0.71 for IFAT. Overall analytical sensitivity was 93.1% and the analytical specificity 96.7%. Overall agreement between the two methods reached 0.97 with a reliability k index of 0.64. CONCLUSION: The DiaMed ELISA test kit shows a good correlation with IFAT for analytical and clinical parameters. It may be an interesting method to replace the IFAT especially in blood banks, but further extensive investigations are needed to examine the analytical performance of the assay, especially in a blood bank setting