Plasma neuronal specific enolase : a potential stage diagnostic marker in human African trypanosomiasis

© The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: [email protected]. Funding: This work was supported through grants from the Wellcome Trust [082786] and Foundation for Innovative New Diagnostics.Peer reviewedPublisher PD

Discovery of Infection Associated Metabolic Markers in Human African Trypanosomiasis

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An extensive endoplasmic reticulum-localised glycoprotein family in trypanosomatids

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A Connectionist Approach to Embodied Conceptual Metaphor

A growing body of data has been gathered in support of the view that the mind is embodied and that cognition is grounded in sensory-motor processes. Some researchers have gone so far as to claim that this paradigm poses a serious challenge to central tenets of cognitive science, including the widely held view that the mind can be analyzed in terms of abstract computational principles. On the other hand, computational approaches to the study of mind have led to the development of specific models that help researchers understand complex cognitive processes at a level of detail that theories of embodied cognition (EC) have sometimes lacked. Here we make the case that connectionist architectures in particular can illuminate many surprising results from the EC literature. These models can learn the statistical structure in their environments, providing an ideal framework for understanding how simple sensory-motor mechanisms could give rise to higher-level cognitive behavior over the course of learning. Crucially, they form overlapping, distributed representations, which have exactly the properties required by many embodied accounts of cognition. We illustrate this idea by extending an existing connectionist model of semantic cognition in order to simulate findings from the embodied conceptual metaphor literature. Specifically, we explore how the abstract domain of time may be structured by concrete experience with space (including experience with culturally specific spatial and linguistic cues). We suggest that both EC researchers and connectionist modelers can benefit from an integrated approach to understanding these models and the empirical findings they seek to explain

Autoimmunity to phosphatidylserine and anemia in African Trypanosome infections

Funding: This work was supported in part by the National Institutes of Health (NIH) institutional training grants 5T32AI100853-03 and 5T32AI007180 to J.R.C. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

A Co-Culturing Approach Enables Discovery and Biosynthesis of a Bioactive Indole Alkaloid Metabolite

FM thanks the University of the Philippines Faculty, Reps, and Staff Development Program (FRASDP) for the PhD grant fellowship. HD and KK are grateful for the financial support of the Leverhulme Trust‐Royal Society Africa award (AA090088) and the jointly funded UK Medical Research Council–UK Department for International Development (MRC/DFID) Concordat Agreement African Research Leaders Award (MR/S00520X/1). RE is grateful to British Council/Newton Fund for financial support through the Institutional Links scheme (Project No. 261781172). QF is grateful to the University of Aberdeen Elphinstone Scholarship and the Scottish Funding Council/ScotCHEM for financial support through PEER/PERCE FundingPeer reviewedPublisher PD

Central Nervous System Parasitosis and Neuroinflammation Ameliorated by Systemic IL-10 Administration in Trypanosoma brucei-Infected Mice

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The relationship of endotoxaemia to peripheral and central nervous system inflammatory responses in Human African Trypanosomiasis

Endotoxaemia has been described in cases of Human African trypanosomiasis (HAT), but it is unclear if this phenomenon influences inflammatory pathology either in the periphery or central nervous system (CNS). We studied endotoxin concentrations in the plasma and cerebrospinal fluid (CSF) of Trypanosoma brucei rhodesiense patients using the chromogenic Limulus Amoebocyte lysate assay. The relationship of endotoxin concentration to the presentation of gross signs of inflammation and the inflammatory/counter-inflammatory cytokine profile of the relevant compartments were analysed. We demonstrate that HAT patients exhibit parasitaemia-independent plasma endotoxaemia, and that this is associated with splenomegaly and lymphadenopathy. Endotoxin concentrations normalize rapidly after treatment. There was no evidence of endotoxin release in the CNS. A rapid normalization of endotoxin levels after treatment and lack of association with parasitaemia suggest that gut leakage is the main source of endotoxin in the circulation. Low CSF endotoxin concentrations and a lack of any association with neuroinflammatory markers or neurological sequelae suggest that endotoxin does not play a role in the pathogenesis of the disease in the CNS

Spatially and genetically distinct African trypanosome virulence variants defined by host interferon-g response

We describe 2 spatially distinct foci of human African trypansomiasis in eastern Uganda. The Tororo and Soroti foci of <i>Trypanosoma brucei rhodesiense</i> infection were genetically distinct as characterized by 6 microsatellite and 1 minisatellite polymorphic markers and were characterized by differences in disease progression and host-immune response. In particular, infections with the Tororo genotype exhibited an increased frequency of progression to and severity of the meningoencephalitic stage and higher plasma interferon (IFN)–γ concentration, compared with those with the Soroti genotype. We propose that the magnitude of the systemic IFN-γ response determines the time at which infected individuals develop central nervous system infection and that this is consistent with the recently described role of IFN-γ in facilitating blood-brain barrier transmigration of trypanosomes in an experimental model of infection. The identification of trypanosome isolates with differing disease progression phenotypes provides the first field-based genetic evidence for virulence variants in T. <i>brucei rhodesiense</i>