EPHA2 mediates PDGFA activity and functions together with PDGFRA as prognostic marker and therapeutic target in glioblastoma

Platelet-derived growth subunit A(PDGFA)plays critical roles in development of glioblastoma(GBM)with substantial evidence from TCGA database analyses and in vivo mouse models.So far,only platelet-derived growth receptor a(PDGFRA)has been identified as receptor for PDGFA.However,PDGFA and PDGFRA are categorized into different molecular subtypes of GBM in TCGA_GBM database.

Evolutionary rates of mitochondrial sequences and gene orders in Spirurina(Nematoda)are episodic but synchronised

In contrast to highly conserved mitogenomic architecture in most metazoan lineages,which indicates that rearrangement events are generally strongly selected against,a limited number of often unrelated lineages exhibit highly elevated architectural evolution rates.The underlying reasons for this discontinuity in the mitogenomic evolution remain unknown.Previously we sequenced the mitochondrial genome of the first Camallanoidea species,Camallanus cotti(Nematoda:Chromadorea:Spirurina:Camallanidae),and found that it exhibited a highly disrupted architecture.We hypothesised that disrupted architecture might be a synapomorphic feature of the sister-clades Camallanoidea and Dracunculoidea.In this study,we sequenced mitogenomes of three freshwater fish-parasitic nematodes:Camallanus lacustris(Camallanidae),and two Philometridae(Dracunculoidea)species,Clavinema parasiluri,and Philometra sp.In partial agreement with the working hypothesis,both Camallanoidea species had exceptionally large mitogenomes of 18–19 Kbp,albeit the underlying reasons differed:in C.lacustris it was the existence of a single enlarged noncoding region of
5.5 Kbp.A segment of this region exhibited an inverted base composition skew,which is indicative of a sequence inversion or recombination event.Camallanidae is the second identified chromadorean(first for Spirurina)family that exhibits within-family protein-coding gene rearrangements,and the absence of trnL1 and trnF may be a synapomorphy for Camallanoidea.The underlying reason for the disrupted architecture of Camallanidae does not appear to be a particular event shared by their common ancestor,but rather an underlying mechanism that makes disruptive events more likely in this lineage.In disagreement with the working hypothesis,Spiruromorpha and Oxyuridomorpha exhibited even more highly rearranged gene orders and greater overall branch lengths than Camallanomorpha.However,withininfraorder architecture was highly conserved and leaf nodes very short.This indicates that common ancestors of Spiruromorpha and Oxyuridomorpha clades underwent a period of rapid mitochondrial evolution(both sequence and architecture),followed by a stabilisation after the taxonomic radiation.In contrast to this,Camallanomorpha,and particularly Camallanidae,appear to have entered a period of elevated evolutionary rates after the initial radiations of these two taxa.As a result of this evolutionary discontinuity,there was a strong correlation between the gene order rearrangement rate(GORR)and the overall branch length(0.81),but there was no correlation between the strength of purifying selection(ω?dN/dS)and the overall branch lengths(0.05)and GORR(0.04).These findings have important repercussions for future phylogenetic and other evolutionary studies of Spirurina.