Biology subjects

Skinner, E.

Publications and source records attributed to Skinner, E..

4 recordsLinked to original sources

bioRxiv2024

Alzheimer's disease-associated genotypes differentially influence chronic evoked seizure outcomes and antiseizure medicine activity in aged mice

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSAlzheimers disease (AD) patients are at greater risk of focal seizures than similarly aged adults; these seizures, left untreated, may worsen functional decline. Older people with epilepsy generally respond well to antiseizure medications (ASMs). However, whether specific ASMs can differentially control seizures in AD is unknown. The corneal kindled mouse model of acquired chronic secondarily generalized focal seizures allows for precisely timed drug administration studies to quantify the efficacy and tolerability of ASMs in an AD-associated genetic model. We hypothesized that mechanistically distinct ASMs would exert differential anticonvulsant activity and tolerability in aged AD mice (8-15 months) to define whether rational ASM selection may benefit specific AD genotypes. METHODSAged male and female PSEN2-N141I versus age-matched non-transgenic control (PSEN2 control) C57Bl/6J mice, and APPswe/PS1dE9 versus transgene negative (APP control) littermates underwent corneal kindling to quantify latency to fully kindled criterion. Dose-related ASM efficacy was then compared in each AD model versus matched control over 1-2 months using ASMs commonly prescribed in older adults with epilepsy: valproic acid, levetiracetam, lamotrigine, phenobarbital, and gabapentin. RESULTSSex and AD genotype differentially impacted seizure susceptibility. Male PSEN2-N141I mice required more stimulations to attain kindling criterion (X2=5.521; p<0.05). Male APP/PS1 mice did not differ in kindling rate versus APP control mice, but they did have more severe seizures. There were significant ASM class-specific differences in acute seizure control and dose-related tolerability. APP/PS1 mice were more sensitive than APP controls to valproic acid, levetiracetam, and gabapentin. PSEN2-N141I mice were more sensitive than PSEN2 controls to valproic acid and lamotrigine. DISCUSSIONAD genotypes may differentially impact ASMs activity and tolerability in vivo with advanced biological age. These findings highlight the heterogeneity of seizure risk in AD and suggest that precisely selected ASMs may beneficially control seizures in AD, thus reducing functional decline.

neuroscience↗

bioRxiv2024

Australian vertebrate hosts of Japanese encephalitis virus; a review of the evidence

Japanese Encephalitis Virus (JEV) transmission in temperate Australia has underscored a critical need to characterise transmission pathways and identify probable hosts of infection within the country. This systematic review consolidates existing research on the vertebrate hosts of JEV that are known to exist in Australia. Specifically, we aim to identify probable species for JEV transmission, their potential role as either a spillover or maintenance host and identify critical knowledge gaps. Data were extracted from studies involving experimental infection, seroprevalence, and virus isolation and were available for 22 vertebrate species known to reside in Australia. A host competence score was calculated to assess the potential for a given species to infect JEV vectors and to quantity their possible role in JEV transmission. Based on the host competence score and ecology of each species, we find ardeid birds, feral pigs, and flying foxes have potential as maintenance hosts for JEV in the Australian context. We also note that brushtail possums and domestic pigs have potential as spillover hosts under certain outbreak conditions. However, evidence to confirm these roles in localized transmission or outbreaks is sparse, emphasizing the need for further targeted research. This review provides a foundation for future investigations into JEV transmission in Australia, advocating for enhanced surveillance and standardized research methodologies to better understand and mitigate the viruss impact.

ecology↗

bioRxiv2022

Temperature impacts on dengue incidence are nonlinear and mediated by climatic and socioeconomic factors

Temperature can influence mosquito-borne diseases like dengue. These effects are expected to vary geographically and over time in both magnitude and direction and may interact with other environmental variables, making it difficult to anticipate changes in response to climate change. Here, we investigate global variation in temperature-dengue relationship by analyzing published correlations between temperature and dengue and matching them with remotely sensed climatic and socioeconomic data. We found that the correlation between temperature and dengue was most positive at intermediate (near 24{degrees}C) temperatures, as predicted from the thermal biology of the mosquito and virus. Positive temperature-dengue associations were strongest when temperature variation and population density were high and decreased with infection burden and rainfall mean and variation, suggesting alternative limiting factors on transmission. Our results show that while climate effects on diseases are context-dependent they are also predictable from the thermal biology of transmission and its environmental and social mediators.

ecology↗

bioRxiv2021

Physiology and ecology combine to determine host and vector importance for Ross River virus and other vector-borne diseases

Identifying the key vector and host species driving transmission is notoriously difficult for vector-borne zoonoses, but critical for disease control. Here, we present a general approach for quantifying the role hosts and vectors play in transmission that integrates species physiological competence with their ecological traits. We apply this model to the medically important arbovirus Ross River virus (RRV), in Brisbane, Australia. We found that vertebrate species with high physiological competence werent the most important for community transmission. Instead, we estimated that humans (previously overlooked as epidemiologically important hosts) potentially play an important role in RRV transmission, in part, because highly competent vectors readily feed on them and are highly abundant. By contrast, vectors with high physiological competence were also important for community transmission. Finally, we uncovered two potential transmission cycles: an enzootic cycle involving birds and an urban cycle involving humans. This modelling approach has direct application to other zoonotic arboviruses.

ecology↗