Philipp Lehrich

Binding Site Distribution of Nuclear Transport Receptors and Transport Complexes in Single Nuclear Pore Complexes

Transport through the nuclear pore complex (NPC) involves a large channel and an abundance of binding sites for nuclear transport receptors (NTRs). However, the mechanistically important distribution of NTR‐binding sites along the channel is vividly debated. In this study, we visualized binding site distributions directly by two complementary optical super‐resolution methods, single‐molecule microscopy and 4Pi microscopy. First, we analyzed the distribution of RanGDP because this important nuclear transport substrate has two types of binding sites at the NPC, direct and indirect, NTR‐mediated sites. We found that the direct binding sites had a maximum at approximately −30 nm with regard to the NPC center, whereas the indirect transport‐relevant binding sites peaked at approximately −10 nm. The 20 nm‐shift could be only resolved by 4Pi microscopy because of a two to threefold improved localization precision as compared with single‐molecule microscopy. Then we analyzed the distribution of the NTR Kapβ1 and a Kapβ1‐based transport complex and found them to have also binding maxima at approximately −10 nm. These observations support transport models in which NTR binding sites are distributed all along the transport channel and argue against models in which the cytoplasmic entrance of the channel is surrounded by a large cloud of binding sites.

Primary Cardiac Angiosarcoma Treated With Positron Emission Tomography/Magnetic Resonance Imaging–Guided Adaptive Radiotherapy

Radiotherapy (RT) for inoperable patients with primary cardiac sarcomas or residual tumor is often limited by the sensitivity of the heart and lung to radiation injury. We describe a novel treatment modality with adaptive radiotherapy (ART) using tumor volume tracking in a 37-year-old woman who presented with unresectable primary cardiac angiosarcoma. The patient was treated using positron emission tomography/magnetic resonance imaging-guided ART with 55.8 Gy concomitant with paclitaxel chemotherapy. In conclusion, the treatment was well tolerated, and a significant tumor volume reduction of ∼ 57% was achieved during radiotherapy, suggesting the effectiveness and tolerability of ART in combination with paclitaxel-based chemotherapy.