Co expression of SCF and KIT in gastrointestinal stromal tumours (GISTs) suggests an autocrine/paracrine mechanism

KIT is a tyrosine kinase receptor expressed by several tumours, which has for specific ligand the stem cell factor (SCF). KIT is the main oncogene in gastrointestinal stromal tumours (GISTs), and gain-of-function KIT mutations are present in 70% of these tumours. The aim of the study was to measure and investigate the mechanisms of KIT activation in 80 KIT-positive GIST patients. KIT activation was quantified by detecting phosphotyrosine residues in Western blotting. SCF production was determined by reverse transcriptase–PCR, ELISA and/or immunohistochemistry. Primary cultures established from three GISTs were also analysed. The results show that KIT activation was detected in all cases, even in absence of KIT mutations. The fraction of activated KIT was not correlated with the mutational status of GISTs. Membrane and soluble isoforms of SCF mRNA were present in all GISTs analysed. Additionally, SCF was also detected in up to 93% of GISTs, and seen to be present within GIST cells. Likewise, the two SCF mRNA isoforms were found to be expressed in GIST-derived primary cultures. Thus, KIT activation in GISTs may in part result from the presence of SCF within the tumours

Updated Definition and Correlation of the Lower Fifteenmile Group in the Central and Eastern Ogilvie Mountains

Ongoing mapping, chemostratigraphy, geochronology, and stratigraphic analysis of Neoproterozoic successions in the Ogilvie Mountains requires redefinition and correlation of the Fifteenmile Group across the Proterozoic inliers in Yukon. Here we present new stratigraphic logs through the lower Fifteenmile Group in the Coal Creek and Hart River inliers. Based on these data and new observations, we propose redefinition of the lower Fifteenmile Group. A succession dominated by sandstone, mapped as unit PPD1 in the Hart River inlier, is now recognized at the base of the Fifteenmile Group in the Coal Creek inlier. These strata unconformably overlie the Pinguicula Group and transition upward into a distinctive carbonate interval; together, these comprise the informally defined Gibben formation. The shallowing-upward carbonate sequence contains abundant oolitic grainstone and packstone and microbial laminated dolostone. It is capped by a distinct interval of mud-cracked maroon mudstone, siltstone, and fine-grained sandstone that forms the base of what we informally define as the Chandindu formation. The mud-cracked shale transitions upwards into interbedded shale, coarse-grained sandstone, and minor carbonate. The overlying informally defined Reefal assemblage consists of up to 1 km of complexly interbedded carbonate and shale, with variable truncation beneath the major angular unconformity at the base of the Callison Lake Dolostone. The lower Fifteenmile Group (now informally PPD1 through the Chandindu formation) likely correlates with the Hematite Creek Group in the Wernecke Mountains.Earth and Planetary Science

Out of Africa: The origins of the protozoan blood parasites of the Trypanosoma cruzi clade found in bats from Africa.

Understanding geographic patterns of interaction between hosts and parasites can provide useful insight into the evolutionary history of the organisms involved. However, poor taxon sampling often hinders meaningful phylogenetic descriptions of groups of parasites. Trypanosome parasites that constitute the Trypanosoma cruzi clade are worldwide distributed infecting several mammalian species, especially bats. Diversity in this clade has been recently expanded by newly discovered species, but the common ancestor and geographical origins of this group of blood parasites are still debated. We present here results based on the molecular characterization of trypanosome isolates obtained from 1493 bats representing 74 species and sampled over 16 countries across four continents. After estimating the appropriate number of hypothetical species in our data set using GMYC models in combination with Poisson Tree Processes (mPTP) and ABGD, the 18S rRNA and gGAPDH genes were used for phylogenetic analyses to infer the major evolutionary relationships in the T. cruzi clade. Then, biogeographical processes influencing the distribution of this cosmopolitan group of parasites was inferred using BioGeoBEARS. Results revealed a large lineages diversity and the presence of trypanosomes in all sampled regions which infected 344 individuals from 31 bat species. We found eight Trypanosoma species, including: five previously known; one subspecies of Trypanosoma livingstonei (Trypanosoma cf. livingstonei); and two undescribed taxa (Trypanosoma sp. 1, Trypanosoma sp. 2), which were found exclusively in bats of the genus Miniopterus from Europe and Africa. The new taxa discovered have both an unexpected position in the global phylogeny of the T. cruzi clade. Trypanosoma sp. 1 is a sister lineage of T. livingstonei which is located at the base of the tree, whereas Trypanosoma sp. 2 is a sister lineage of the Shizotrypanum subclade that contains T. c. cruzi and T. dionisii. Ancestral areas reconstruction provided evidence that trypanosomes of the T. cruzi clade have radiated from Africa through several dispersion events across the world. We discuss the impact of these findings on the biogeography and taxonomy of this important clade of parasites and question the role played by bats, especially those from the genus Miniopterus, on the dispersal of these protozoan parasites between continents