Dysregulated eIF4E-dependent translation is a central driver of tumorigenesis and therapy resistance. eIF4E binding proteins (4E-BP1/2/3) are major negative regulators of eIF4E-dependent translation that are inactivated in tumors through inhibitory phosphorylation or downregulation. Previous studies have linked PP2A phosphatase(s) to activation of 4E-BP1.
View Article and Find Full Text PDFPurpose: Mesothelin (MSLN) is highly expressed in high grade serous/ endometrioid ovarian cancers (HGOC). Anetumab ravtansine (AR) is an antibody drug conjugate directed at MSLN antigen with a tubulin polymerization inhibitor. We assessed safety, activity and pharmacokinetics of the combination AR/bevacizumab (Bev) (ARB) versus weekly paclitaxel (wP)/Bev (PB) in patients with platinum resistant/refractory HGOC (prrHGOC).
View Article and Find Full Text PDFRoman writers found the relative empowerment of Celtic women remarkable. In southern Britain, the Late Iron Age Durotriges tribe often buried women with substantial grave goods. Here we analyse 57 ancient genomes from Durotrigian burial sites and find an extended kin group centred around a single maternal lineage, with unrelated (presumably inward migrating) burials being predominantly male.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
The dynamic response of heterogeneous catalytic materials to their environment opens a wide variety of possible surface states which may have increased catalytic activity. In this work, we find that it is possible to generate a surface state with increased catalytic activity over metallic 2 nm Pt nanoparticles by performing a thermal treatment of the CO*-covered Pt catalyst. This state is characterised by its ability to oxidise CO to CO at room temperature.
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