Biology subjects

Nichols, R.

Publications and source records attributed to Nichols, R..

3 recordsLinked to original sources

bioRxiv2022

The rVSV-EBOV vaccine provides limited cross-protection against Sudan virus in guinea pigs

Recombinant vesicular stomatitis viruses (rVSVs) engineered to express heterologous viral glycoproteins have proven to be remarkably effective vaccines. Indeed, rVSV-EBOV, which expresses the Ebola virus (EBOV) glycoprotein, recently received clinical approval in the United States and Europe for its ability to prevent EBOV disease. Analogous rVSV vaccines expressing the glycoproteins of different human-pathogenic filoviruses have also been developed and shown to be effective in pre-clinical evaluations, yet these vaccine candidates have not progressed far beyond research laboratories. As the current outbreak of Sudan virus (SUDV) intensifies in Uganda, the need for proven countermeasures is rendered even more acute. Here we demonstrate that an rVSV-based vaccine expressing the SUDV glycoprotein (rVSV-SUDV) generates a potent humoral immune response that completely protects guinea pigs from SUDV disease and death. Although the cross-protection generated by rVSV vaccines for different filoviruses is thought to be limited, we wondered whether rVSV-EBOV might also provide protection against SUDV, which is closely related to EBOV. Surprisingly, nearly 60% of guinea pigs that were vaccinated with rVSV-EBOV and challenged with SUDV survived, suggesting that rVSV-EBOV offers limited protection against SUDV, at least in the guinea pig model. These results were confirmed by a back-challenge experiment in which animals that had been vaccinated with rVSV-EBOV and survived EBOV challenge were inoculated with SUDV and survived. Whether these data are applicable to the efficacy of rVSV-EBOV in humans is unknown, and they should therefore be interpreted cautiously. Nevertheless, this study confirms the potency of the rVSV-SUDV vaccine, and it highlights the potential for rVSV-EBOV to elicit a cross-protective immune response.

microbiology↗

bioRxiv2020

The Neuroprotective Beta Amyloid Hexapeptide Core Reverses Deficits in Synaptic Plasticity in the 5xFAD APP/PS1 Mouse Model

Alzheimers disease (AD) is the most common cause of dementia in the aging population. Evidence implicates elevated soluble oligomeric A{beta} as one of the primary triggers during the prodromic phase leading to AD, effected largely via hyperphosphorylation of the microtubule-associated protein tau. At low, physiological levels (pM-nM), however, oligomeric A{beta} has been found to regulate synaptic plasticity as a neuromodulator. Through mutational analysis, we found a core hexapeptide sequence within the N-terminal domain of A{beta} (N-A{beta}core) accounting for its physiological activity, and subsequently found that the N-A{beta}core peptide is neuroprotective. Here, we characterized the neuroprotective potential of the N-A{beta}core against dysfunction of synaptic plasticity assessed in ex vivo hippocampal slices from 5xFAD APP/PS1 mice, specifically hippocampal long-term potentiation (LTP) and long-term depression (LTD). The N-A{beta}core was shown to reverse impairment in synaptic plasticity in hippocampal slices from 5xFAD APP/PS1 model mice, both for LTP and LTD. The reversal by the N-A{beta}core correlated with alleviation of downregulation of hippocampal AMPA-type glutamate receptors in preparations from 5xFAD mice. The action of the N-A{beta}core depended upon a critical di-histidine sequence and involved the PI3 kinase pathway via mTOR. Together, the present findings indicate that the non-toxic N-A{beta}core hexapeptide is not only neuroprotective at the cellular level but is able to reverse synaptic dysfunction in AD-like models, specifically alterations in synaptic plasticity.

neuroscience↗

bioRxiv2020

Genomic architecture and evolutionary conflict drive allele-specific expression in the social supergene of the red fire ant

Supergenes are genomic regions of suppressed recombination that underlie complex polymorphisms. Despite the importance of such regions, our empirical understanding of their early evolution is limited. The young "social" supergene of the fire ant Solenopsis invicta provides a powerful system for disentangling the roles of evolutionary conflict and the implications of suppressed recombination. We used population genomics to identify genetic differences between supergene variants and gene expression analyses across different populations, castes and body parts to characterize allelic expression differences for the hundreds of genes in the supergene. We find that the expression of most genes is independent of social form or supergene variant, in line with the young age of this system. Many of the genes with allelic expression differences, however, show a pattern consistent with gene degeneration due to suppressed recombination. In contrast, a small portion of the genes has the signature of evolutionary conflict between social forms.

molecular biology↗