Biology subjects

Ma, Y.-F.

Publications and source records attributed to Ma, Y.-F..

3 recordsLinked to original sources

bioRxiv2024

DNA Prime-Protein Boost Targeting Conformational Non-RBD Region for Broad Cross-Neutralization

Preventing immune escape of SARS-CoV-2 variants is crucial in vaccine development to ensure broad protection against the virus. Conformational epitopes beyond the RBD region are vital components of the spike protein but have received limited attention in the development of broadly protective SARS-CoV-2 vaccines. In this study, we used a DNA prime-protein boost regimen to evaluate the broad cross-neutralization potential of immune response targeting conformational non-RBD region against SARS-CoV-2 viruses in mice. Mice with enhanced antibody responses targeting conformational non-RBD region show better performance in cross-neutralization against the Wuhan-01, Delta, and Omicron subvariants. Via analyzing the distribution of conformational epitopes, and quantifying epitope-specific binding antibodies, we verified a positive correlation between the proportion of binding antibodies against the N-terminal domain (NTD) supersite (a conformational non-RBD epitope) and SARS-CoV-2 neutralization potency. The current work highlights the importance of high ratio of conformational non-RBD-specific binding antibodies in mediating viral cross-neutralization and provides new insight into overcoming the immune escape of SARS-CoV-2 variants.

immunology↗

bioRxiv2019

Pathogenicity of urinary tract infection Escherichia coli in Caenorhabditis elegans

Uropathogenic Escherichia coli (UPEC) is a major bacterial pathogen that causes urinary tract infections (UTIs). Several virulence factors (VFs) in the bacteria have been associated with the pathogenicity. The mouse is an available UTI model for studying the pathogenicity; however, Caenorhabditis elegans represents as an alternative surrogate host for studying UPEC with the capacity for high-throughput analysis. Therefore, we established a simple assay for a UPEC infection model with C. elegans for large-scale screening. An E. coli culture to be tested and synchronized C. elegans were mixed in 96-well plates, and the pathogenicity was determined by comparison of the turbidity before and after incubation. A total of 133 clinically isolated E. coli strains, which included UTI-associated and fecal isolates, were applied to demonstrate the liquid pathogenicity assay. The E. coli isolates associated with UTIs showed higher pathogenicity in C. elegans than the fecal isolates, suggesting that the simple assay with C. elegans is useful as a UPEC infectious model. From the screening, VFs involved with iron acquisition (chuA, fyuA, and irp2) were significantly associated with high pathogenicity. C. elegans is a heme auxotroph, and iron homeostasis also serves innate immunity in C. elegans. We then evaluated whether the VFs in UPEC were involved in the pathogenicity. Mutants of E. coli UTI89 with defective iron acquisition systems were applied to a solid killing assay with C. elegans. As a result, the survival rate of C. elegans fed with the mutants significantly increased compared to when fed with the parent strain. To our knowledge, this is the first report of the involvement of iron acquisition in the pathogenicity of UPEC in a C. elegans model.

microbiology↗

bioRxiv2019

Convergent genomic signatures of high altitude adaptation among domestic mammals

Abundant and diverse domestic mammals living on the Tibetan Plateau provide useful materials for investigating adaptive evolution and genetic convergence. Here, we utilized 327 genomes from horses, sheep, goats, cattle, pigs and dogs living at both high and low altitudes, including 73 genomes generated for this study, to disentangle the genetic mechanisms underlying local adaptation of domestic mammals. Although molecular convergence is comparatively rare at the DNA sequence level, we found convergent signature of positive selection at the gene level, particularly EPAS1 gene in these Tibetan domestic mammals. We also reported a potential function in response to hypoxia for the gene C10orf67, which underwent positive selection in three of the domestic mammals. Our data provides insight into adaptive evolution of high-altitude domestic mammals, and should facilitate the search for additional novel genes involved in the hypoxia response pathway.

evolutionary biology↗