Three is the magic number -- distance measurement of NGC 3147 using SN 2021hpr and its siblings

The nearby spiral galaxy NGC 3147 hosted three Type Ia supernovae (SNe Ia) in the past decades, which have been subjects of intense follow-up observations. Simultaneous analysis of their data provides a unique opportunity for testing the different light curve fitting methods and distance estimations. The detailed optical follow-up of SN 2021hpr allows us to revise the previous distance estimations to NGC 3147, and compare the widely used light curve fitting algorithms to each other. After the combination of the available and newly published data of SN 2021hpr, its physical properties can be also estimated with higher accuracy. We present and analyse new BVgriz and Swift photometry of SN 2021hpr to constrain its general physical properties. Together with its siblings, SNe 1997bq and 2008fv, we cross-compare the individual distance estimates of these three SNe given by the SALT code, and also check their consistency with the results from the MLCS2k2 method. The early spectral series of SN 2021hpr are also fit with the radiative spectral code TARDIS in order to verify the explosion properties and constrain the chemical distribution of the outer ejecta. After combining the distance estimates for the three SNe, the mean distance to their host galaxy, NGC 3127, is 42.5 $\pm$ 1.0 Mpc, which matches with the distance inferred by the most up-to-date LC fitters, SALT3 and BayeSN. We confirm that SN~2021hpr is a Branch-normal Type Ia SN that ejected $\sim 1.12 \pm 0.28$ M$_\odot$ from its progenitor white dwarf, and synthesized $\sim 0.44 \pm 0.14$ M$_\odot$ of radioactive $^{56}$Ni.Comment: 16 pages, 17 figures, 11 tables; accepted for publication in A&

Impaired Cytoplasmic Domain Interactions Cause Co-Assembly Defect and Loss of Function in the p.Glu293Lys KNCJ2 Variant Isolated from an Andersen-Tawil Syndrome Patient

Aims: Subunit interactions at the cytoplasmic domain interface (CD-I) have recently been shown to control gating in in-ward rectifier potassium channels. Here we report the novel KCNJ2 variant p.Glu293Lys that has been found in a patient with Andersen–Tawil syndrome type 1 (ATS1), causing amino acid substitution at the CD-I of the inward rectifier potassium channel subunit Kir2.1. Neither has the role of Glu293 in gating control been investigated nor has a pathogenic variant been described at this position. This study aimed to assess the involvement of Glu293 in CD-I subunit interactions and to establish the pathogenic role of the p.Glu293Lys variant in ATS1. Methods and results: The p.Glu293Lys variant produced no current in homomeric form and showed dominant-negative effect over wild-type (WT) subunits. Immunocytochemical labelling showed the p.Glu293Lys subunits to distribute in the subsarco-lemmal space. Salt bridge prediction indicated the presence of an intersubunit salt bridge network at the CD-I of Kir2.1, with the involvement of Glu293. Subunit interactions were studied by the NanoLucVR Binary Technology (NanoBiT) split reporter assay. Reporter constructs carrying NanoBiT tags on the intracellular termini produced no bioluminescent signal above background with the p.Glu293Lys variant in homomeric configuration and significantly reduced signals in cells co-expressing WT and p.Glu293Lys subunits simultaneously. Extracellularly presented reporter tags, however, generated comparable bioluminescent signals with heteromeric WT and p.Glu293Lys subunits and with homomeric WT channels. Conclusions: Loss of function and dominant-negative effect confirm the causative role of p.Glu293Lys in ATS1. Co-assembly of Kir2.1 subunits is impaired in homomeric channels consisting of p.Glu293Lys subunits and is partially rescued in het�eromeric complexes of WT and p.Glu293Lys Kir2.1 variants. These data point to an important role of Glu293 in mediating subunit assembly, as well as in gating of Kir2.1 channels