Biology subjects

O'Hara, E.

Publications and source records attributed to O'Hara, E..

4 recordsLinked to original sources

bioRxiv2025

Antigenic Mapping of H2 Influenza Viruses recognized by Ferret and Human Sera and Predicting Antigenically Significant Sites

Influenza viruses cause hundreds of thousands of infections globally every year. In the past century, seasonal influenza viruses have included H1N1, H2N2 and H3N2 strains. H2N2 influenza viruses circulated in the human population between 1957-1968. Previously, our group demonstrated a lack of H2N2 influenza virus immunity in individuals born after 1968, as well as the effectiveness of hemagglutinin (HA) based vaccines for multiple influenza virus subtypes. In this study, H2 antigenic maps and radial graphs were generated using previously published data from H2 HA vaccinations of ferrets and seasonal influenza vaccinations of humans. The antigenic maps revealed a stark difference in clustering of HA antigens between the ferrets and humans, and the radial graphs showed specific antigen recognition varies greatly between different influenza preimmune ferrets. These maps also revealed the significant impact that different pre-existing immunities have on antigenic recognition and clustering of antigens after vaccine boost. From these data, we predicted two possible antigenically significant sites containing various mutations that have not been previously reported and showed that one of these sites is relevant using mouse anti-sera. ImportanceH2N2 influenza viruses have caused at least one known pandemic in humans and are poised to cause future pandemics. Investigating the antigenic diversity of H2 HA proteins provides valuable data for designing and understanding the performance of current and future vaccines. Data evaluating the difference in antigen recognition across species and pre-existing immunity can be used to predict antigenically significant sites and evaluate the impact of H1 and H3 infection and immune imprinting on H2 vaccine immunogenicity. This information can direct future studies when both extrapolating animal data to human studies and creating next generation vaccines. Contrasting the relationships between new, contemporary and ancestral H2 HA antigens by antigenic cartography is imperative for identifying new variants of concern and updating vaccine formulations.

microbiology↗

bioRxiv2022

Comparative analysis of macroalgae supplementation on the rumen microbial community: Asparagopsis taxiformis inhibits major ruminal methanogenic, fibrolytic, and volatile fatty acid-producing microbes in vitro

1.Seaweeds have received a great deal of attention recently for their potential as methane-suppressing feed additives in ruminants. To date, Asparagopsis taxiformis has proven a potent enteric methane inhibitor, but it is a priority to identify local seaweed varieties that may hold similar properties. It is essential that any methane inhibitor does not compromise the function of the rumen microbiome. In this study, we conducted an in vitro experiment using the RUSITEC system to evaluate the impact of A. taxiformis, Palmaria mollis, and Mazzaella japonica on rumen prokaryotic communities. 16S rRNA sequencing showed that A. taxiformis had a profound effect on the microbiome, particularly on methanogens. Weighted Unifrac distances showed significant separation of A. taxiformis samples from the control and other seaweeds (P<0.05). Neither P. mollis nor M. japonica had a substantial effect on the microbiome (P>0.05). A. taxiformis reduced the abundance of all major archaeal species (P<0.05), leading to an almost total disappearance of the methanogens. Prominent fibre-degrading and volatile fatty acid (VFA)-producing bacteria including Fibrobacter and Ruminococcus were also inhibited by A. taxiformis (P<0.05), as were other genera involved in propionate production. However, the abundance of many other major bacteria (e.g. Prevotella) was increased by A. taxiformis suggesting the rumen microbiome adapted to an initial perturbation. Our study provides baseline knowledge of microbial dynamics in response to seaweed feeding over an extended period and suggests that feeding A. taxiformis to cattle to reduce methane may directly or indirectly inhibit important fibre-degrading and VFA-producing bacteria.

microbiology↗

bioRxiv2022

An NKX-COUP-TFII genomic code for mucosal vascular addressins and organ morphogenesis

Immunoglobulin family and carbohydrate vascular addressins encoded by Madcam1 and St6gal1 control lymphocyte homing into intestinal tissues, regulating immunity and inflammation. The addressins are developmentally programmed to decorate endothelial cells lining gut post-capillary and high endothelial venules, providing a prototypical example of organ- and segment-specific endothelial specialization. We identify conserved NKX-COUP-TFII composite elements (NCCE) in regulatory regions of Madcam1 and St6gal1 that bind intestinal homeodomain protein NKX2-3 cooperatively with venous nuclear receptor COUP-TFII to activate transcription. The Madcam1 element also integrates repressive signals from arterial/capillary Notch effectors. Pan-endothelial COUP-TFII overexpression induces ectopic addressin expression in NKX2-3+ capillaries, while NKX2-3 deficiency abrogates expression by HEV. Phylogenetically conserved NCCE are enriched in genes involved in neuron migration and morphogenesis of the heart, kidney, pancreas and other organs. Our results define a genomic address code for targeted expression of mucosal vascular addressins and implicate NCCE in fundamental processes in cell specification and development.

immunology↗

bioRxiv2020

A molecular map of lymph node blood vascular endothelium at single cell resolution

Blood vascular endothelial cells (BECs) control the immune response by regulating immune cell recruitment, metabolite exchange and blood flow in lymphoid tissues. However, the diversity of BEC and their origins during immune angiogenesis remain poorly understood. Here we profile transcriptomes of BEC from mouse peripheral lymph nodes and map key phenotypes to the vasculature. Our analysis identifies multiple novel subsets including a venous population whose gene signature predicts an unexpectedly selective role in myeloid cell (vs lymphocyte) recruitment to the medulla, confirmed by 2 photon videomicroscopy. We define five phenotypes of capillary lining BEC including a capillary resident regenerative population (CRP) that displays stem cell and migratory gene signatures and contributes to homeostatic BEC turnover and to vascular neogenesis after immunization. Trajectory analyses reveal retention of developmental programs along a progression of cellular phenotypes from CRP to mature venous and arterial BEC subsets. Overall, our single cell atlas provides a molecular blueprint of the lymph node blood vasculature and defines subset specialization for immune cell recruitment and vascular homeostasis.

immunology↗