Erythropoietin (EPO) is a glycoprotein cytokine known for its pleiotropic effects on various types of cells and tissues. EPO and its receptor EPOR trigger signaling cascades JAK2/STAT5, MAPK, and PI3K/AKT that are interconnected and irreplaceable for cell survival. In this article, we describe the role of the MAPK and PI3K/AKT signaling pathways during red blood cell formation as well as in non-hematopoietic tissues and tumor cells. Although the central framework of these pathways is similar for most of cell types, there are some stage-specific, tissue, and cell-lineage differences. We summarize the current state of research in this field, highlight the novel members of EPO-induced PI3K and MAPK signaling, and in this respect also the differences between erythroid and non-erythroid cells.

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Here we demonstrate an interaction between neural precursor cell expressed, developmentally-downregulated 9 (NEDD9) and the cytoskeletal proteins vimentin and non-muscle myosin IIA (NMIIA), based on co-immunoprecipitation and mass spectrometric sequence identification. Vimentin was constitutively phosphorylated at Ser56 but vimentin associated with NEDD9-was not phosphorylated at Ser56. In contrast, NMIIA bound to NEDD9 was phosphorylated on S1943 consistent with its function in invasion and secretion. Treatment of cells with the vimentin-targeting steroidal lactone withaferin A had no effect on vimentin turnover as previously reported, instead causing NEDD9 cleavage and cell death. The NMIIA-selective inhibitor blebbistatin induced cells to form long extensions and attenuated secretion of matrix metalloproteinases (MMPs) 2 and 9. While the site of vimentin interaction on NEDD9 was not defined, NMIIA was found to interact with NEDD9 at its substrate domain. NEDD9 interactions with vimentin and NMIIA are consistent with these proteins having roles in MMP secretion and cell invasion. These findings suggest that a better understanding of NEDD9 signaling is likely to reveal novel therapeutic targets for the prevention of invasion and metastasis.

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Mass hibernacula of several tens of thousands of

The refugial history and postglacial re‐colonization routes of Western Carpathian insects are insufficiently understood. Therefore, we investigated the spatio‐genetic structure (phylogeography) of Western Carpathian populations of Erebia euryale (Esper, 1805) (Lepidoptera, Nymphalidae) and inferred their colonization routes over the postglacial period. Our results provide new insights into the phylogeography and origin of Erebia euryale in the rarely studied region of the Western Carpathian Mountains. Their phylogeography, including glacial refugia and Pleistocene expansion routes, was reconstructed based on two mitochondrial (COI and CR) and three nuclear markers (CAD, MDH and IDH). Statistical parsimony networks showed the following geographic coherences: (1) populations from Romania and the Bukovské Mountains (Kremenec) grouped together; (2) a Čergov group containing populations only from the Čergov Mountains; (3) a Volovské Mountains group with populations from Kojšovská hoľa and Slovak Paradise grouped together, most likely due to the lack of geographic isolation between the areas; (4) haplotypes characterized from the Volovské Mountains populations were widespread. Comparisons of Western Carpathian E. euryale COI‐haplotypes with haplotypes from the Southern Carpathians and Balkans suggest that the refugial areas were located in south‐eastern Europe in the Balkan region and Southern Carpathians. We also hypothesize possible central European contact zones in Slovakia for E. euryale in the Western Carpathians. Our results indicate that the Western Carpathians could have served as one of the contact zones between Eastern and Western populations, and additionally as an extra refugium in the southern part of the Volovské Mountains for populations also occurring in Czech mountain regions.

The distribution of genetic diversity within Erebia pronoe (Esper, 1780) populations in relation to biogeographic ranges is essential for understanding the processes of evolution, speciation and phylogeography in this species. A certain degree of genetic variability was expected because of the species’ linkage solely to calcareous soils. These ideas were focused on the water ringlet E. pronoe, a European endemic montane butterfly distributed over a narrow area of mountains, with its occurrence dependent on nutrient plants. Therefore, the origin, occurrence, phylogeography and variability are described in defined mountain localities in Europe in the light of glaciation events that occurred during the Quaternary (Pleistocene) period. The species’ phylogeography is based on a combination of two mitochondrial genes (COI, CR) and morphology (wing morphometry). The study comprised samples from the Western Carpathians, Pyrenees, Alps, South-Eastern Carpathians (Romania) and Southern Limestone Alps (Slovenia). Moreover, the species’ remarkable phylogeographic structure was observed, including four morphologic lineages and divergent genetic lineages. These lineages cover the Carpathian Mountains as well as the Western European mountains (Spanish populations) with no apparent gene flow between most regions, even across distances of only hundreds of kilometres.