Nudel and FAK as Antagonizing Strength Modulators of Nascent Adhesions through Paxillin

Competition for binding to the cellular protein paxillin by the proteins Nudel and focal adhesion kinase is important for the proper regulation of cell adhesion and migration

Linking the northern Alps with their foreland: The latest exhumation history resolved by low-temperature thermochronology

The evolution of the Central Alpine deformation front (Subalpine Molasse) and its undeformed foreland is recently debated because of their role for deciphering the late orogenic evolution of the Alps. Its latest exhumation history is poorly understood due to the lack of late Miocene to Pliocene sediments. We constrain the late Miocene to Pliocene history of this transitional zone with apatite fission track and (U-Th)/He data. We used laser ablation inductively coupled mass spectrometry for apatite fission track dating and compare this method with previously published and unpublished external detector method fission track data. Two investigated sections across tectonic slices show that the Subalpine Molasse was tectonically active after the onset of folding of the Jura Mountains. This is much younger than hitherto assumed. Thrusting occurred at 10, 8, 6–5 Ma and potentially thereafter. This is contemporaneous with reported exhumation of the External Crystalline Massifs in the central Alps. The Jura Mountains and the Subalpine Molasse used the same detachments as the External Crystalline Massifs and are therefore kinematically coupled. Estimates on the amount of shortening and thrust displacement corroborate this idea. We argue that the tectonic signal is related to active shortening during the late stage of orogenesis

FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements

FGFR2 rearrangements resulting in dysregulated signaling are drivers of cholangiocarcinoma (CCA) tumorigenesis, and occur almost exclusively in intrahepatic CCA. Pemigatinib, a selective, potent, oral inhibitor of FGFR1-3, has demonstrated efficacy and safety in a Phase II study of patients with previously treated locally advanced/metastatic CCA harboring FGFR2 fusions/rearrangements. We describe the study design of FIGHT-302, an open-label, randomized, active-controlled, multicenter, global, Phase III study comparing the efficacy and safety of first-line pemigatinib versus gemcitabine plus cisplatin in patients with advanced CCA with FGFR2 rearrangements (NCT03656536). The primary end point is progression-free survival; secondary end points are objective response rate, overall survival, duration of response, disease control rate, safety and quality of life