Pathogen-sugar interactions revealed by universal saturation transfer analysis

Many pathogens exploit host cell-surface glycans. However, precise analyses of glycan ligands binding with heavily modified pathogen proteins can be confounded by overlapping sugar signals and/or compounded with known experimental constraints. Universal saturation transfer analysis (uSTA) builds on existing nuclear magnetic resonance spectroscopy to provide an automated workflow for quantitating protein-ligand interactions. uSTA reveals that early-pandemic, B-origin-lineage severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike trimer binds sialoside sugars in an "end-on" manner. uSTA-guided modeling and a high-resolution cryo-electron microscopy structure implicate the spike N-terminal domain (NTD) and confirm end-on binding. This finding rationalizes the effect of NTD mutations that abolish sugar binding in SARS-CoV-2 variants of concern. Together with genetic variance analyses in early pandemic patient cohorts, this binding implicates a sialylated polylactosamine motif found on tetraantennary N-linked glycoproteins deep in the human lung as potentially relevant to virulence and/or zoonosis

Improving software quality through computer supported collaborative review

Formal technical review (FTR) is a cornerstone of software quality assurance. However, the labor-intensive and manual nature of review, along with basic unresolved questions about its process and products, means that review is typically under-utilized or inefficiently applied within the software development process. This paper introduces CSRS, a computer-supported cooperative work environment for software review that improves the efficiency of review activities and supports empirical investigation of the appropriate parameters for review. The paper presents a typical scenario of CSRS in review, its data and process model, application to process maturation, relationship to other research, current status, and future directions. 1