Semelfactives are bigger than degree achievements: The nanosyntax of Czech and Polish semelfactive and degree achievement verb stems

This paper argues that semelfactive and degree achievement verbs are morphosyntactically distinct, despite the fact that the morphemes they are made of are often syncretic even in languages with synthetic verb morphology like Czech or Polish. We use the mechanisms of Nanosyntax, a theory of the architecture of grammar in which the lexicon stores entire syntactic subtrees, to show that there is a structural containment between semelfactives and degree achievements such that semelfactives include more syntactic structure than degree achievements. In this respect, the relative structure of these two verb classes contributes to Bobaljik’s (2012) general claim that syncretism anchors structural containment as well as to the ongoing discussion about the form of spell out in syntax. The resulting picture supports the view whereby the semantics of lexical items is determined by their fine-grained internal syntax

Identification of a MET-eIF4G1 translational regulation axis that controls HIF-1α levels under hypoxia.

Poor oxygenation is a common hallmark of solid cancers that strongly associates with aggressive tumor progression and treatment resistance. While a hypoxia-inducible factor 1α (HIF-1α)-associated transcriptional overexpression of the hepatocyte growth factor (HGF) receptor tyrosine kinase (RTK) MET has been previously documented, any regulation of the HIF-1α system through MET downstream signaling in hypoxic tumors has not been yet described. By using MET-driven in vitro as well as ex vivo tumor organotypic fresh tissue models we report that MET targeting results in depletion of HIF-1α and its various downstream targets. Mechanistically, we provide evidence that MET regulates HIF-1α levels through a protein translation mechanism that relies on phosphorylation modulation of the eukaryotic initiation factor 4G1 (eIF4G1) on serine 1232 (Ser-1232). Targeted phosphoproteomics data demonstrate a significant drop in eIF4G1 Ser-1232 phosphorylation following MET targeting, which is linked to an increased affinity between eIF4G1 and eIF4E. Since phosphorylation of eIF4G1 on Ser-1232 is largely mediated through mitogen-activated protein kinase (MAPK), we show that expression of a constitutively active K-RAS variant is sufficient to abrogate the inhibitory effect of MET targeting on the HIF-1α pathway with subsequent resistance of tumor cells to MET targeting under hypoxic conditions. Analysis of The Cancer Genome Atlas data demonstrates frequent co-expression of MET, HIF-1α and eIF4G1 in various solid tumors and its impact on disease-free survival of non-small cell lung cancer patients. Clinical relevance of the MET-eIF4G1-HIF-1α pathway is further supported by a co-occurrence of their expression in common tumor regions of individual lung cancer patients