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Biology subjects

Boyce, R.

Publications and source records attributed to Boyce, R..

5 recordsLinked to original sources

Crop-specific agricultural land use and Rift Valley fever outbreaks in Uganda: a longitudinal compositional analysis

Rift Valley fever (RVF) is a mosquito-borne disease that can cause severe illness and death in both humans and livestock. Since 2016, Uganda has experienced recurrent but localized RVF outbreaks concentrated in the countrys southwestern region. The ecological drivers of this emergence remain unclear, as outbreaks have occurred throughout the year and show little association with meteorological patterns. We evaluated whether crop cultivation, particularly banana cultivation, is associated with RVF outbreak occurrence after controlling for likely confounders. We conducted a longitudinal study of human-inhabited 5 x 5 km grid cells across southwestern Uganda from 2016-2024. Annual Sentinel-2 satellite imagery composites were used to classify land cover into banana, coffee, ground crops, and non-crop categories, and the proportion of each land type was calculated for every grid-cell year. Because land cover proportions are compositional, isometric log-ratio transformations were used to estimate the independent effects of each land type. Confounding was addressed through propensity weighting, and crop substitution effects were estimated using g-computation. Banana land cover was the only land type consistently associated with increased RVF outbreak likelihood. In grid-cell years with low baseline banana cover, a 10-percentage point substitution from other land classes into banana was associated with a 1.64-fold increase in the odds of an RVF outbreak (95% CI: 1.17-2.29). In a simplified banana-only model, each 10-percentage point increase in banana cover was associated with a 1.21-fold increase in outbreak odds (95% CI: 1.02-1.43). Holding banana cover constant, substitutions among coffee, ground crop, and non-crop land showed weak or null associations. These findings suggest that banana cultivation may be an important ecological feature influencing RVF transmission dynamics and outbreak risk in southwestern Uganda. Author SummaryRift Valley fever (RVF) is a mosquito-borne disease that affects both humans and livestock and has caused repeated outbreaks in southwestern Uganda since 2016. While rainfall and flooding are often linked to RVF outbreaks elsewhere, Ugandas recent outbreaks have occurred across seasons and are not well explained by weather patterns alone. We investigated whether agricultural land use could help explain where outbreaks occur. Using satellite imagery from 2016-2024, we measured the amount of banana cultivation, coffee cultivation, ground crops, and non-crop land across southwestern Uganda and evaluated their association with RVF outbreak occurrence. We found that areas with greater banana cultivation were consistently more likely to experience RVF outbreaks, even after accounting for environmental and demographic factors. In contrast, coffee, ground crops, and non-crop land showed little evidence of an independent association with outbreak risk. These findings suggest that banana cultivation may create ecological conditions that favor RVF transmission. Rather than indicating that bananas themselves cause disease, the results point to banana-growing landscapes as potential environments where interactions among mosquitoes, livestock, and humans may increase transmission opportunities. Understanding these local ecological drivers could help improve surveillance, risk assessment, and prevention strategies for RVF in Uganda and other endemic regions.

ecology↗

Identification and Characterization of Novel Chikungunya Virus Polymerase Inhibitors

Chikungunya virus (CHIKV) and other alphaviruses in the Togaviridae family are positive-sense RNA viruses and major human pathogens, causing millions of infections worldwide. In humans, alphaviruses such as CHIKV, Mayaro and Ross River viruses typically cause arthritogenic disease characterized by debilitating arthralgia, joint inflammation, fever, and rash. Although a vaccine was recently approved for use against CHIKV, no vaccines are licensed against other alphaviruses. No antiviral treatments are available to prevent or treat infections by any alphavirus. To address this unmet need, we used a CHIKV nanoluciferase reporter virus to develop a high-throughput screening assay for novel small-molecule inhibitors. From this campaign, we identified several unique inhibitors of CHIKV replication. Mechanistic characterization of two inhibitors revealed that both target the nsP4 RNA-dependent RNA polymerase, while susceptibility profiling pinpointed unique nsP4 mutations that specifically confer resistance. In silico docking analyses indicated potential binding poses of the inhibitors near the polymerase active site. Collectively, these results define multiple chemotypes for further development and highlight novel molecular targets within nsP4 for CHIKV inhibition. IMPORTANCEChikungunya virus is a mosquito-borne pathogen that has caused millions of human infections worldwide, producing severe fever, rash, and long-lasting joint pain that can persist for months. Related viruses such as Mayaro and Ross River viruses also cause debilitating disease, yet no antiviral drugs are available to treat any infection caused by this family of viruses. In this study, we developed a high-throughput assay that allowed us to rapidly identify compounds capable of blocking chikungunya virus replication. We discovered new hit compounds that inhibit virus growth. In addition, we determined that two of the most promising hit candidates target the viral nsP4 polymerase. By identifying these novel inhibitors and characterizing both their mechanisms of action and resistance profiles, we have established the groundwork for future efforts to develop much needed therapies against chikungunya virus and related pathogens.

molecular biology↗

Cortical neuronal assemblies coordinate with EEG microstate dynamics during resting wakefulness.

The disruption of cortical assembly activity has been associated with anesthesia-induced loss of consciousness. However, information about the relationship between cortical assembly activity and the variations in consciousness associated with natural vigilance states is currently lacking. To address this, we performed vigilance state-specific clustering analysis on 2-photon calcium imaging data from sensorimotor cortex in combination with global EEG microstate analysis derived from multi-EEG signals obtained from widespread cortical locations. Our analysis revealed no difference in the structure of assembly activity during quiet wakefulness (QW), NREMs, or REMs, despite the latter two vigilance states being associated with significantly reduced levels of consciousness relative to QW. However, we found a significant coordination between global EEG microstate dynamics and local cortical assembly activity during periods of QW, but not sleep. These results suggest that the coordination of cortical assembly activity with global brain dynamics could be a key factor of sustained conscious experience.

neuroscience↗

Spatial memory consolidation during REM sleep requires stabilization of newly formed place cells.

The involvement of rapid-eye-movement sleep (REMs) in spatial memory formation was recently demonstrated, although how neural activity during REMs influences newly-formed place field stability remains unclear. Here, we combined large-scale single-unit recordings of mouse hippocampal CA1 with an established optogenetic approach enabling REMs-selective inhibition of medial septum GABAergic neurons (MSGABA), resulting in spatial memory deficits when applied post-learning. Although individual neural activity was unaffected by REMs-selective MSGABA inhibition during a post-learning rest session, both the synchrony of population-level activity bursts observed during REMs occurring in the rest session and place field stability measured during subsequent memory recall testing were reduced vs controls. However, the latter effect was limited to place cells participating in population activity during REMs, as stability of non-participant place cells was relatively weak and indifferent between groups. This suggests that synchronous CA1 population activity during REMs stabilizes spatial representations in a plastic subpopulation of participating CA1 neurons.

neuroscience↗

Dynamical modulation of theta-gamma coupling during REM sleep

Theta phase modulates gamma amplitude during spatial navigation and rapid eye movement sleep (REMs). Although the REMs theta rhythm has been linked to spatial memory consolidation, the underlying mechanism remains unclear. We investigate dynamics of theta-gamma interactions across multiple frequency and temporal scales in simultaneous recordings from hippocampal CA3, CA1, subiculum, and parietal cortex. We show that theta phase significantly modulates three distinct gamma bands during REMs, dynamically. Interestingly, we further show that theta-gamma coupling swings between different hippocampal and cortical structures during REMs and tends to increase over a single REMs episode. Comparing to active wake, theta-gamma coupling during REMs is significantly increased for subicular and cortical, but not for CA3 and CA1, recordings. Finally, optogenetic silencing of septohippocampal GABAergic projections significantly impedes both theta-gamma coupling and theta phase coherence, two neural mechanisms of working and long-term memory, respectively. Thus, we show that theta-gamma coupling and theta phase coherence are highly modulated during single REMs episode and propose that theta-gamma coupling provides a predominant mechanism for information processing within each brain region, while the orchestrated nature of coupling activity establishes a specific phase-space coding of information during sleep.

neuroscience↗