Using a site-specific mass spectrometric approach, scientists from the University of Southampton analyze the glycan-processing states of the spike (S) glycoprotein used by SARS-CoV-2 to infect human cells, uncovering details that may help guide the development of vaccines against the virus. The SARS-CoV-2 S gene encodes 22 N-linked glycan sequons per protomer, which likely play a role in protein folding and immune evasion, the scientists write in Science. To understand the site-specific glycosylation of the viral S protein and visualize the distribution of glycoforms across the protein surface, they expressed and purified recombinant glycosylated spike complexes from which glycopeptides containing a single N-linked glycan sequon were generated. The team then used liquid-chromatography-mass spectrometry to analyze the glycopeptides, revealing the glycan structures on a recombinant SARS-CoV-2 S immunogen and showing how "SARS-CoV-2 S glycans differ from typical host glycan processing, which may have implications in viral pathobiology and vaccine design."
Alcohol intake and genetic mutations appear to influence the prevalence of gastric cancers in East Asians, according to a study appearing in Science Advances. A University of Tokyo-led team performed a genomic-scale trans-ethnic analysis of 531 gastric cancers in 319 Asians and 212 non-Asians, with 243 samples taken from Japanese patients and analyzed using whole-genome sequencing. The scientists find that about one-fifth of diffuse-type gastric cancers were attributable to either a combination of alcohol intake and defects in the ALDH2 allele predominant in Asian populations, or to germline loss-of-function variants of the CDH1 gene. "Our findings clarified previously unrecognized impacts of the defined germline and lifestyle factors on the high incidences of [gastric cancers] in East Asian areas and provided us strong motivations for clinical intervention in lifestyles and familial cares coupled with precision germline genotyping in these areas," the investigators write.