Ultra-sensitive and selective Hg2+ chemosensors derived from substituted 8-hydroxyquinoline analogues

International audienceNovel analogues of 8-hydroxyquinoline with phosphinate or thiophosphinate functions and styryl fluorophores in the para position to the nitrogen atom were prepared via multi-step syntheses, using phosphorylation and Wittig coupling reactions. A strong affinity between the quinoline analogues and heavy metal ions such as Pb2+, Cd2+ and Hg2+ was highlighted. The interaction of the metal ions with the nitrogen of the styrylquinoline leads to a large red shift of the absorption and emission spectra in agreement with an increase of the photoinduced charge transfer character of the styryl fluorophore. In the presence of metal ions the appearance of a green fluorescence emission is also observed upon excitation at 420 nm or 840 nm, thanks to a significant increase of the two-photon response. Under optimal conditions, a mercury concentration of 15 ppt in a partially aqueous medium can be detected using the thiophosphinate derivative without interference from other metal ions

Genome-wide Meta-analysis Unravels Novel Interactions between Magnesium Homeostasis and Metabolic Phenotypes

Magnesium (Mg <sup>2+</sup> ) homeostasis is critical for metabolism. However, the genetic determinants of the renal handling of Mg <sup>2+</sup> , which is crucial for Mg <sup>2+</sup> homeostasis, and the potential influence on metabolic traits in the general population are unknown. We obtained plasma and urine parameters from 9099 individuals from seven cohorts, and conducted a genome-wide meta-analysis of Mg <sup>2+</sup> homeostasis. We identified two loci associated with urinary magnesium (uMg), rs3824347 (P=4.4×10 <sup>-13</sup> ) near TRPM6, which encodes an epithelial Mg <sup>2+</sup> channel, and rs35929 (P=2.1×10 <sup>-11</sup> ), a variant of ARL15, which encodes a GTP-binding protein. Together, these loci account for 2.3% of the variation in 24-hour uMg excretion. In human kidney cells, ARL15 regulated TRPM6-mediated currents. In zebrafish, dietary Mg <sup>2+</sup> regulated the expression of the highly conserved ARL15 ortholog arl15b, and arl15b knockdown resulted in renal Mg <sup>2+</sup> wasting and metabolic disturbances. Finally, ARL15 rs35929 modified the association of uMg with fasting insulin and fat mass in a general population. In conclusion, this combined observational and experimental approach uncovered a gene-environment interaction linking Mg <sup>2+</sup> deficiency to insulin resistance and obesity

Glycosylation is a key in SARS-CoV-2 infection

SARS-CoV-2 causes the respiratory syndrome COVID-19 and is responsible for the current pandemic. The S protein of SARS-CoV-2-mediating virus binding to target cells and subsequent viral uptake is extensively glycosylated. Here we focus on how glycosylation of both SARS-CoV-2 and target cells crucially impacts SARS-CoV-2 infection at different levels: (1) virus binding and entry to host cells, with glycosaminoglycans of host cells acting as a necessary co-factor for SARS-CoV-2 infection by interacting with the receptor-binding domain of the SARS-CoV-2 spike glycoprotein, (2) innate and adaptive immune response where glycosylation plays both a protective role and contributes to immune evasion by masking of viral polypeptide epitopes and may add to the cytokine cascade via non-fucosylated IgG, and (3) therapy and vaccination where a monoclonal antibody-neutralizing SARS-CoV-2 was shown to interact also with a distinct glycan epitope on the SARS-CoV-2 spike protein. These evidences highlight the importance of ensuring that glycans are considered when tackling this disease, particularly in the development of vaccines, therapeutic strategies and serological testing