Biology subjects

Harrison, M. B.

Publications and source records attributed to Harrison, M. B..

3 recordsLinked to original sources

bioRxiv2026

Oral 4`fluorouridine provides postexposure protection against lethal Nipah virus infection

There are no approved medical countermeasures for combatting Nipah virus (NiV) which causes regular outbreaks in humans and animals in South and Southeast Asia with mortality rates in humans ranging from 40% to more than 90%. Recently, it was shown that 4-fluorouridine (4-FlU; EIDD-2749), an orally available ribonucleoside analog, protected guinea pigs and nonhuman primates from lethal challenge with Lassa virus and that 4-FlU has in vitro antiviral activity against NiV. Here, we assessed the postexposure protective efficacy of 4-FlU in a lethal hamster model of NiV infection. Daily treatment with 4-FlU beginning 3 days after exposure to NiV resulted in complete protection from lethal infection. Our findings support the further development of 4-FlU as a therapy for NiV disease.

microbiology↗

bioRxiv2020

Hippocampal and cortical mechanisms at retrieval explain variability in episodic remembering in older adults

Age-related episodic memory decline is characterized by striking heterogeneity across individuals. Hippocampal pattern completion is a fundamental process supporting episodic memory. Yet, the degree to which this mechanism is impaired with age, and contributes to variability in episodic memory, remains unclear. We combine univariate and multivariate analyses of fMRI data from a large cohort of cognitively normal older adults (N=100; 60-82 yrs) to measure hippocampal activity and cortical reinstatement during retrieval of trial-unique associations. Trial-wise analyses revealed that hippocampal activity predicted cortical reinstatement strength, and these two metrics of pattern completion independently predicted retrieval success. However, increased age weakened cortical reinstatement and its relationship to memory behaviour. Critically, individual differences in the strength of hippocampal activity and cortical reinstatement explained unique variance in performance across multiple assays of episodic memory. These results indicate that fMRI indices of hippocampal pattern completion explain within- and across-individual memory variability in older adults.

neuroscience↗

bioRxiv2018

Altered cortical brain structure and increased risk for disease seen decades after perinatal exposure to maternal smoking: A study of 9,000 adults in the UK Biobank

Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44-80) who were exposed (n=2,510) or unexposed (n=6,079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volume. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE-) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n=109, unexposed, n=315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

neuroscience↗