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    A Soluble Factor from Trypanosoma cruzi Inhibits Transforming Growth Factor-ß-Induced MAP Kinase Activation and Gene Expression in Dermal Fibroblasts
    (2011) Costales Cordero, Jaime Alfredo; Mott, Adam G.
    The protozoan parasite Trypanosoma cruzi, which causes human Chagas´disease, exerts a variety of effects on host extracellular matrix (ECM) including proteolytic degradation of collagens and dampening of ECM gene expression. Exposure of primary human dermal fibroblasts to live infective T. cruzi trypomastigotes or their shed/secreted products results in a rapdi down-regulation of the fibrogenic genes collagen a1, fibronectin and connective tissue growth factor (CTGF/CCN2). Here we demonstrate the ability of a secreted/released T. cruzi factor to antagonize ctgf/ccn2 expression in dermal fibroblasts in response to TGF-B, lysophosphatidic acid or serum, where agonist-induced phosphorylation of the mitogen-activated protein (MAP) kinases Erk1/2, p38 and JNK was also inhibited. Global analysis of gene expression in dermal fibroblasts identified a discrete subset of TGF-B-inducible genes involved in cell proliferation, wound repair, and immune regulation that are inhibited by T. cruzi secreted/released factors, where the genes exhibiting the highest sensitivity to T. cruzi are known to be regulated by MAP kinase-activated transcription factors. Consistent with this observation, the Ets-family transcription factor binding site in the proximal promoter region of the ctgf/ccn2 gene (-91bp to -84 bp) was shown to be required for T. cruzi-mediated down-regulation of ctgf/ccn2 reporter expression. The cumulative data suggest a model in which T. cruzi-derived molecules secreted/released early in the infective process dampen MAP kinase signaling and the activation of transcription factors that regulate expression of fibroblast genes invoved in wound repair and tissue remodelling, including ctfg/ccn2. These findings have broader implications for local modulation of ECM synthesis/remodelling by T. cruzi during the early establishment of infection in the mammalian host and highlight the potencial for pathogen-derived molecules to be exploited as tools to modulate the fibrogenic response.
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    Ecological and genetic divergence between two lineages of Middle American túngara frogs Physalaemus (=Engystomops) pustulosus
    (2010) Ron Melo, Santiago Rafael; Pröhl, Heike.
    Uncovering how populations of a species differ genetically and ecologically is important for understanding evolutionary processes. Here we combine population genetic methods (microsatellites) with phylogenetic information (mtDNA) to define genetic population clusters of the wide-spread Neotropical túngara frog (Physalaemus pustulosus). We measure gene flow and migration within and between population clusters and compare genetic diversity between population clusters. By applying ecological niche modeling we determine whether the two most divergent genetic groups of the túngara frog (1) inhabit different habitats, and (2) are separated geographically by unsuitable habitat across a gap in the distribution. Most population structure is captured by dividing all sample localities into two allopatric genetic lineages. The Northern genetic lineage (NW Costa Rica) is genetically homogenous while the Southern lineage (SW Costa Rica and Panama) is sub-divided into three population clusters by both microsatellite and mtDNA analyses. Gene flow is higher within the Northern lineage than within the Southern lineage, perhaps due to increased landscape heterogeneity in the South. Niche modeling reveals differences in suitable habitat between the Northern and Southern lineages: the Northern lineage inhabits dry/pine-oak forests, while the Southern lineage is confined to tropical moist forests. Both lineages seem to have had little movement across the distribution gap, which persisted during the last glacial maximum. The lack of movement was more pronounced for the Southern lineage than for the Northern lineage. This study confirms the finding of previous studies that túngara frogs diverged into two allopatric genetic lineages north and south of the gap in the distribution in central Costa Rica several million years ago. The allopatric distribution is attributed to unsuitable habitat and probably other unknown ecological factors present across the distribution gap. Niche conservatism possibly contributes to preventing movements across the gap and gene flow between both groups. Genetic and ecological data indicate that there is the potential for ecological divergence in allopatry between lineages. In this context we discuss whether the Northern and Southern lineages should be recognized as separate species, and we conclude that further studies of pre- and post-zygotic isolation are needed for a final assessment. Identified population clusters should motivate future behavioral and ecological research regarding within-species biodiversity and speciation mechanisms.
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    The Impact of Conservation on the Status of the World´s Vertebrates
    (2010) Ron Melo, Santiago Rafael; Hoffman, Michael
    Using data for 25,780 species categorized on the International Union for Conservation of Nature Red List, we present an assessment of the status of the world’s vertebrates. One-fifth of species are classified as Threatened, and we show that this figure is increasing: On average, 52 species of mammals, birds, and amphibians move one category closer to extinction each year. However, this overall pattern conceals the impact of conservation successes, and we show that the rate of deterioration would have been at least one-fifth again as much in the absence of these. Nonetheless, current conservation efforts remain insufficient to offset the main drivers of biodiversity loss in these groups: agricultural expansion, logging, overexploitation, and invasive alien species.