The regions within the N-terminus critical for human glucagon like peptide-1 receptor (hGLP-1R) cell Surface expression

The hGLP-1R is a target for the treatment of type 2 diabetes and belongs to the class B family of GPCRs. Like other class B GPCRs, the GLP-1R contains an N-terminal signal peptide (SP) and undergoes N-linked glycosylation, which are important for its trafficking and maturation. This study analysed the role of the SP, the hydrophobic region after the SP (HRASP), glycosylation and the conserved residues within the N-terminus in GLP-1R trafficking. HGLP-1R targeted to the cell surface showed no SP, and the SP deleted mutant, but not the mutants defective in SP cleavage, showed cell surface expression, demonstrating the importance of SP cleavage for hGLP-1R cell surface expression. The N-terminal deletions of hGLP-1R revealed that the HRASP, not the SP, is essential for cell surface expression of GLP-1R. Further, inhibition of hGLP-1R glycosylation prevented cell surface expression of the receptor. Mutation of Trp39, Tyr69 and Tyr88, which are required for agonist binding, in the GLP-1R abolished cell surface expression of the receptor independent of the SP cleavage or N-linked glycosylation. In conclusion, the N-terminus of hGLP-1R regulates receptor trafficking and maturation. Therefore this study provides insight into the role of hGLP-1R N-terminus on the receptor cell surface expression

Evaluation of candidate models for the 13th generation International Geomagnetic Reference Field

In December 2019, the 13th revision of the International Geomagnetic Reference Field (IGRF) was released by the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group V-MOD. This revision comprises two new spherical harmonic main field models for epochs 2015.0 (DGRF-2015) and 2020.0 (IGRF-2020) and a model of the predicted secular variation for the interval 2020.0 to 2025.0 (SV-2020-2025). The models were produced from candidates submitted by fifteen international teams. These teams were led by the British Geological Survey (UK), China Earthquake Administration (China), Universidad Complutense de Madrid (Spain), University of Colorado Boulder (USA), Technical University of Denmark (Denmark), GFZ German Research Centre for Geosciences (Germany), Institut de physique du globe de Paris (France), Institut des Sciences de la Terre (France), Pushkov Institute of Terrestrial Magnetism, Ionosphere and Radio Wave Propagation (Russia), Kyoto University (Japan), University of Leeds (UK), Max Planck Institute for Solar System Research (Germany), NASA Goddard Space Flight Center (USA), University of Potsdam (Germany), and Université de Strasbourg (France). The candidate models were evaluated individually and compared to all other candidates as well to the mean, median and a robust Huber-weighted model of all candidates. These analyses were used to identify, for example, the variation between the Gauss coefficients or the geographical regions where the candidate models strongly differed. The majority of candidates were sufficiently close that the differences can be explained primarily by individual modeling methodologies and data selection strategies. None of the candidates were so different as to warrant their exclusion from the final IGRF-13. The IAGA V-MOD task force thus voted for two approaches: the median of the Gauss coefficients of the candidates for the DGRF-2015 and IGRF-2020 models and the robust Huber-weighted model for the predictive SV-2020-2025. In this paper, we document the evaluation of the candidate models and provide details of the approach used to derive the final IGRF-13 products. We also perform a retrospective analysis of the IGRF-12 SV candidates over their performance period (2015–2020). Our findings suggest that forecasting secular variation can benefit from combining physics-based core modeling with satellite observations

International Geomagnetic Reference Field: the thirteenth generation

In December 2019, the International Association of Geomagnetism and Aeronomy (IAGA) Division V Working Group (V-MOD) adopted the thirteenth generation of the International Geomagnetic Reference Field (IGRF). This IGRF updates the previous generation with a definitive main field model for epoch 2015.0, a main field model for epoch 2020.0, and a predictive linear secular variation for 2020.0 to 2025.0. This letter provides the equations defining the IGRF, the spherical harmonic coefficients for this thirteenth generation model, maps of magnetic declination, inclination and total field intensity for the epoch 2020.0, and maps of their predicted rate of change for the 2020.0 to 2025.0 time period

Special issue "International Geomagnetic Reference Field: the thirteenth generation"

International audienc