Biology subjects

Fox, M. J.

Publications and source records attributed to Fox, M. J..

3 recordsLinked to original sources

bioRxiv2026

Vaccination of pregnant mares with mRNA encoding a GPI-anchored form of the virulence-associated protein A of Rhodococcus equi induces strong IgG responses that are transferred to their foals

The bacterium Rhodococcus equi is a common cause of severe pneumonia in foals worldwide. Foals are exposed to R. equi from birth and are most susceptible in the first weeks of life. In North America, control measures are limited to transfusion to newborn foals of hyperimmune plasma whose potency is assessed by surpassing a threshold of IgG against the virulence-associated protein A (VapA) of R. equi. Here we report results of vaccination of pregnant mares with mRNA encoding a GPI-anchored virulence-associated protein A (VapA) of R. equi induced VapA-specific IgG subisotypes transferred to their foals during the 63-day period after birth. Pregnant mares were randomly assigned to receive either VapA mRNA vaccine (n=10) at 8 and 10 months of gestation or no vaccine (n=10). Serum was collected from mares at 8 months of gestation (before vaccination for immunized mares) and {approx}24 hours after foaling and from foals at ages 1, 35, and 63 days. Mean relative concentrations of were low before immunization in all mares and did not change over time in unvaccinated mares; however, mean relative concentrations of anti-VapA IgG1, IgG4/7, and IgG3/5 of mares were significantly increased after VapA mRNA immunization and strongly correlated with the corresponding concentrations in their foals sera at age {approx}24 hours. Concentrations of anti-VapA IgGs remained increased in foals of vaccinated mares compared with control foals for at least 35 days.

immunology↗

bioRxiv2019

RNA Polymerase II CTD phosphatase Rtr1 prevents premature transcription termination

RNA Polymerase II (RNAPII) transcription termination is regulated by the phosphorylation status of the C-terminal domain (CTD). Using disruption-compensation (DisCo) protein-protein interaction network analysis, interaction changes were observed within the termination machinery as a consequence of deletion of the serine 5 RNAPII CTD phosphatase Rtr1. Interactions between RNAPII and the cleavage factor IA (CF1A) subunit Pcf11 were reduced in rtr1{Delta}, whereas interactions with the CTD and RNA-binding termination factor Nrd1 were increased. These changes could be the result of altered interactions between the termination machinery and/or increased levels of premature termination of RNAPII. Transcriptome analysis in rtr1{Delta} cells found decreased pervasive transcription and a shift in balance of expression of sense and antisense transcripts. Globally, rtr1{Delta} leads to decreases in noncoding RNAs that are linked to the Nrd1, Nab3 and Sen1 (NNS)-dependent RNAPII termination pathway. Genome-wide analysis of RNAPII and Nrd1 occupancy suggests that loss of RTR1 leads to increased termination at noncoding genes and increased efficiency of snRNA termination. Additionally, premature termination increases globally at protein-coding genes where NNS is recruited during early elongation. The effects of rtr1{Delta} on RNA expression levels were erased following deletion of the exosome subunit Rrp6, which works with the NNS complex to rapidly degrade terminated noncoding RNAs. Overall, these data suggest that Rtr1 restricts the NNS-dependent termination pathway in WT cells to prevent premature RNAPII termination of mRNAs and ncRNAs. Additionally, Rtr1 phosphatase activity facilitates low-level elongation of noncoding transcripts that impact the transcriptome through RNAPII interference.\n\nAUTHOR SUMMARYMany cellular RNAs including those that encode for proteins are produced by the enzyme RNA Polymerase II. In this work, we have defined a new role for the phosphatase Rtr1 in the regulation of RNA Polymerase II progression from the start of transcription to the 3 end of the gene where the nascent RNA from protein-coding genes is typically cleaved and polyadenylated. Deletion of the gene that encodes RTR1 leads to changes in the interactions between RNA polymerase II and the termination machinery. Rtr1 loss also causes early termination of RNA Polymerase II at many of its target gene types including protein coding genes and noncoding RNAs. Evidence suggests that the premature termination observed in RTR1 knockout cells occurs through the termination factor and RNA binding protein Nrd1 and its binding partner Nab3. Additionally, many of the prematurely terminated noncoding RNA transcripts are degraded by the Rrp6-containing nuclear exosome, a known component of the Nrd1-Nab3 termination coupled RNA degradation pathway. These findings suggest that Rtr1 normally promotes elongation of RNA Polymerase II transcripts through preventation of Nrd1-directed termination.

systems biology↗

bioRxiv2018

Effects of Orientation Change during Environmental Learning on Age-Related Difference in Spatial Memory

It has been suggested that older adults suffer a greater degree of decline in environmental learning when navigating in an environment than when reading a map of the environment. However, the two types of spatial learning differ not only in perspectives (i.e., navigation is done with a ground-level perspective; a map is read from an aerial perspective) but also in orientations (i.e., orientations vary during navigation; spatial information is drawn from a single orientation in a map), making it unclear which factor critically affects older adults spatial learning. The present study addressed this issue by having younger and older participants learn the layout of a large-scale environment through an aerial movie that contained changes in orientations from which the environment was depicted. Results showed that older participants memories for the environmental layout were as distorted as those created through a ground-level movie (which involved the same orientation changes), whereas they formed more accurate memories through another aerial movie in which an orientation was fixed. By contrast, younger participants learned the environment equally well from the three movies. Taken together, these findings suggest that there is age-related alteration specifically in the ability to process multiple orientations of an environment while encoding its layout in memory. It is inferred that this alteration stems from functional deterioration of the medial temporal lobe, and possibly that of posterior cingulate areas as well (e.g., the retrosplenial cortex), in late adulthood.

neuroscience↗