The role of mycelium production and a MAPK-mediated immune response in the C. elegans-Fusarium model system

Fusariosis is an emerging infectious complication of immune deficiency, but models to study this infection are lacking. The use of the soil nematode Caenorhabditis elegans as a model host to study the pathogenesis of Fusarium spp. was investigated. We observed that Fusarium conidia consumed by C. elegans can cause a lethal infection and result in more than 90% killing of the host within 120 hours, and the nematode had a significantly longer survival when challenged with Fusarium proliferatum compared to other species. Interestingly, mycelium production appears to be a major contributor in nematode killing in this model system, and C. elegans mutant strains with the immune response genes, tir-1 (encoding a protein containing a TIR domain that functions upstream of PMK-1) and pmk-1 (the homolog of the mammalian p38 MAPK) lived significantly shorter when challenged with Fusarium compared to the wild type strain. Furthermore, we used the C. elegans model to assess the efficacy and toxicity of various compounds against Fusarium. We demonstrated that amphotericin B, voriconazole, mancozeb, and phenyl mercury acetate significantly prolonged the survival of Fusarium-infected C. elegans, although mancozeb was toxic at higher concentrations. In conclusion, we describe a new model system for the study of Fusarium pathogenesis and evolutionarily preserved host responses to this important fungal pathogen.     

Bcr-abl signals to desensitize chronic myeloid leukemia cells to IFNα via accelerating the degradation of its receptor

Constitutive activity of Bcr-abl fusion protein kinase causes chronic myeloid leukemia (CML). Inhibitors of Bcr-abl such as imatinib mesylate have replaced the cytokine IFNα as the primary treatment for the management of patients with this malignancy. We found that pretreatment of CML cells with imatinib mesylate augments the antigrowth effects of IFNα. Furthermore, introduction of Bcr-abl into non-CML cells inhibits the cellular responses to IFNα. This inhibition is mediated via a mechanism that involves activation of protein kinase D2. The latter promotes an accelerated phosphorylation-dependent degradation of the interferon-α/β receptor 1 chain of the type I interferon receptor, leading to attenuation of IFNα signaling. We discuss the relationship between Bcr-abl activity and IFNα signaling as a molecular basis of the combination of inhibitors of Bcr-abl and IFNα for CML treatment.     

The neural time course of art perception: an ERP study on the processing of style versus content in art

A central prerequisite to understand the phenomenon of art in psychological terms is to investigate the nature of the underlying perceptual and cognitive processes. Building on a study by Augustin, Leder, Hutzler, and Carbon (2008) the current ERP study examined the neural time course of two central aspects of representational art, one of which is closely related to object- and scene perception, the other of which is art-specific: content and style. We adapted a paradigm that has repeatedly been employed in psycholinguistics and that allows one to examine the neural time course of two processes in terms of when sufficient information is available to allow successful classification. Twenty-two participants viewed pictures that systematically varied in style and content and conducted a combined go/nogo dual choice task. The dependent variables of interest were the Lateralised Readiness Potential (LRP) and the N200 effect. Analyses of both measures support the notion that in the processing of art style follows content, with style-related information being available at around 224 ms or between 40 and 94 ms later than content-related information. The paradigm used here offers a promising approach to further explore the time course of art perception, thus helping to unravel the perceptual and cognitive processes that underlie the phenomenon of art and the fascination it exerts.