Biology subjects

Wade, A.

Publications and source records attributed to Wade, A..

9 recordsLinked to original sources

bioRxiv2026

Molecular epidemiology of the globally spreading genetic lineage IV of peste des petits ruminants virus

Peste des petits ruminants (PPR) is a highly contagious viral disease of small ruminants caused by the peste des petits ruminants virus (PPRV), which is classified into four distinct genetic lineages (I-IV). A critical concern in the recent epidemiological history of PPRV is the rapid and widespread expansion of lineage IV (LIV) across West Africa over the past decade. This dominance suggests a potential adaptive advantage of circulating LIV strains in the regions current epidemiological context. In this study, we obtain the genome sequence of 26 new PPRV samples, including historical (pre-2000) and many recent African LIV isolates, offering the first opportunity to investigate the evolutionary history of LIV in Africa and identify genetic events potentially associated with its recent spread. Phylogenomic analyses implemented on a dataset of 167 curated PPRV genome sequences reveal that the most ancestral LIV group comprises strains circulating in Sub-Saharan Africa (designated clade LIVssa), providing robust evidence for an African origin of lineage IV. Our results further indicate that PPRV strains linked to the recent West African expansion of LIV belong to a specific LIVssa subgroup, termed NigB. We identified multiple signatures of selection pressure within the LIVssa sublineage, particularly in the NigB cluster. Several amino acid substitutions unique to LIVssa or NigB were detected, some of which may impact protein function and warrant prioritised investigation. Additional genomic data are required to confirm the association between the NigB group and the ongoing spread of LIV in West Africa. The evolutionary adaptations observed in LIVssa - potentially enhancing transmission efficiency, host range or pathogenicity - could undermine current disease control strategies in regions where PPR poses significant threats to food security and local economies. Author SummaryPeste des petits ruminants virus (PPRV) infects sheep and goats across Africa, Middle East, Asia and Europe, causing disease with major impact on global economy and food security. One genetic lineage of PPRV, called lineage IV (LIV), is at the origin of most recent expansion of the distribution of the disease, including replacement of other lineages in areas of African where PPRV is historically present. Here, we generated genome sequences from PPRV LIV isolates from different dates and places to study the evolution of this genetic lineage and explore whether its recent spread can be associated with the appearance of new mutations in the virus genome. Our results provide evidence that the PPRV LIV originated in Sub-Saharan Africa and identify mutations present only virus isolates currently spready in new regions of Africa. Further research should investigate the impact of these mutations on protein functions and capacity of transmission of PPRV.

evolutionary biology↗

bioRxiv2026

NON-REDUNDANT ROLES OF COPPER TRANSPORTERS ATP7A AND ATP7B IN NORADRENERGIC SIGNALING

Menkes disease and Wilson disease are debilitating neurometabolic disorders caused by mutations in the copper (Cu) transporters ATP7A and ATP7B, respectively. In either disease, normalization of systemic Cu levels often does not eliminate neurological deficits, suggesting dysregulated Cu homeostasis within vulnerable neuronal populations. However, the specific roles of ATP7A and ATP7B and the extent of their functional redundancy in neurons remain poorly defined. Here, we selectively deleted Atp7a or Atp7b in noradrenergic neurons, which express both transporters and require Cu for catecholamine biosynthesis. ATP7A deletion reduced Cu levels in the locus coeruleus, disrupted dopamine-{beta}-hydroxylase localization, impaired norepinephrine synthesis, and induced proteomic signatures of defective vesicular trafficking and proteostasis, culminating in neurodegeneration and impaired regulation of energy balance and adaptive thermogenesis. In contrast, ATP7B deletion preserved Cu levels but altered intracellular Cu utilization, resulting in catecholamine imbalance, -synuclein upregulation, aberrant dopamine-{beta}-hydroxylase distribution, and dysregulated thermogenesis. These findings establish ATP7A and ATP7B as non-redundant regulators of noradrenergic function within neural circuits governing metabolic and energy homeostasis and provide a mechanistic framework for persistent neurological pathology independent of systemic Cu levels.

physiology↗

bioRxiv2025

Steady-State Visually Evoked Potentials as Readouts for Abnormal GSK3β Activity in Drosophila

Glycogen synthase kinase 3{beta} (GSK3{beta}) is important in neuronal development and maintenance, acting as a key regulator by controlling a broad range of cellular processes. The effects of its dysregulation range from impairments in axonal transport and energy metabolism to synapse formation and neuronal plasticity. However, how such cellular defects link to neuronal dysfunction is less well studied despite the links between GSK3{beta} and various neurological conditions, such as Alzheimers and Parkinsons diseases, mood disorders and autism. Here we used a steady-state visually evoked potential (SSVEP) assay with Drosophila to measure the effect of altering GSK3{beta} expression on neuronal function. We recorded SSVEPs from flies that expressed constitutively active or inactive (kinase-dead) variants of GSK3{beta} and showed that the visual responses of these flies differed from those of controls. This was indicated by increased response latency and reduced photoreceptor maximum response (Rmax). Importantly, multivariate pattern classification can distinguish between over- and inactive GSK3{beta} conditions. Taken together, we show that SSVEPs provide a powerful tool for future studies to link the molecular and cellular functions of GSK3{beta} with their effects on neuronal function. Furthermore, we introduce a monitoring protocol that ensures the quality of datasets to support future fly SSVEP experiments.

neuroscience↗

bioRxiv2025

Combining phenomic and genomic selection for pea breeding improvement

Pea (Pisum sativum L.) is a strategic crop in the development of sustainable agriculture. However, the genetic gain remains limited despite advances in breeding. Genomic selection holds promise to accelerate varietal improvement, but its high implementation cost restricts its use in crops. Phenomic selection, based on near-infrared spectroscopy data, is a cost-effective alternative demonstrated in various crops, but not yet undertaken in pea. This study aims to assess the predictive ability of phenomic selection, alone and combined with genomic selection, for yield-related traits in a panel of elite spring pea lines evaluated across twelve environments. Three cross-validation scenarios were implemented to simulate predictions across different years and locations. Our results show that phenomic prediction is as effective as genomic selection at predicting yield, and is more accurate for seed protein content. The integrative model, combining spectral and molecular data, consistently achieved the highest accuracy for most traits, particularly for complex traits such as grain yield and seed protein. In temporal prediction scenarios, the most accurate predictions were obtained using the spectra data from the same year as phenotyping. In spatial prediction scenarios, predictive accuracy varied by site and year, nevertheless, integrative phenomic-genomic models consistently outperformed univariate approaches. These findings confirm the potential of phenomic selection in pea and underscore the added value of combining near-infrared spectroscopy and genotyping data to improve the prediction of complex traits in breeding programs. In the face of increasing environmental variability, the integrative approach offers a valuable tool for accelerating genetic gain. Key messageThe integration of spectral data into prediction models enhances the predictive ability for complex traits in pea.

genetics↗

bioRxiv2025

Persistent cortical excitatory neuron dysregulation in adult Chd8 haploinsufficient mice.

CHD8 mutations cause autism spectrum disorder, cognitive deficits, and macrocephaly. Chd8+/- mouse models exhibit macrocephaly and transcriptional pathology, with inconsistent findings regarding neurogenesis, neuron function, and behavior. Via stereology and single nucleus transcriptomics (snRNA-seq), we found increased Chd8+/- cortical volume was not explained by increase in neuron number. Differential expression (DE) was present across cortical cell types, with excitatory neurons exhibiting high DE burden and shared and subclass-specific DE signatures. Bulk RNA-seq DE of constitutive Chd8+/- and conditional Camk2a-Cre Chd8+/-mice identified shared transcriptional pathology. DE in synaptosomal versus nuclear mRNA identified overlapping DEGs, but also significant differences and exaggerated synaptosomal changes. Building on DE findings implicating glutamatergic neurons, we found Chd8+/-mice exhibited altered excitatory neuron spine density and dynamics, decreased GCaMP activity correlation, and sleep perturbation. Thus, Chd8 haploinsufficiency causes lasting excitatory neuron dysfunction, perturbs RNA regulation beyond transcription, and impacts neuronal properties, cortical microcircuits, and behavior.

genomics↗

bioRxiv2025

Cardiorespiratory fitness and cardiometabolic health are associated with distinct cognitive domains in cognitively healthy older adults.

BackgroundAging is associated with progressive cognitive decline, as well as increased prevalence of cardiometabolic risk factors and reduced cardiorespiratory fitness. In fact, reduced cardiometabolic health and cardiorespiratory fitness are both associated with a decline in cognitive functioning. This study examines the common and distinct contributions of these cardiovascular health factors on cognitive variability across different domains in cognitively healthy older adults. Methods and ResultsWe apply structural equation modelling (SEM) to model cross-sectional relationships between cardiometabolic health, cardiorespiratory fitness and performance across multiple cognitive domains in an age-restricted sample of healthy older adults from the ACTIVate Study (n=345; 60-70 yrs). Participants completed a series of cognitive and clinical assessments (including brachial blood pressure, heart rate, blood-based metabolic markers). We designed a cognitive model (Model 1) with four latent factors that are differentially impacted by aging (Processing Speed, Executive Function, Verbal Memory and Crystallized Ability) and used it to test effects on cognition of two theory-driven dimensions of cardiovascular health: Cardiorespiratory Fitness (Model 2) and Cardiometabolic Health (Model 3). Model 4 included both predictors and examined their joint and distinct effects on these cognitive domains. When controlling for their joint variance, Cardiometabolic Health and Cardiorespiratory Fitness showed evidence consistent with a double dissociation on cognitive domains. Specifically, cardiorespiratory fitness significantly predicted processing speed (r=0.28, p<0.05) and executive function (r=0.66, p<0.05), but not verbal memory and crystallized ability. In contrast, cardiometabolic health predicted crystallized ability (r=0.31, p<0.05) and verbal memory (r=0.28, p<0.05), but not executive function and processing speed. ConclusionsThis study shows the first evidence that cardiorespiratory fitness and cardiometabolic health are associated with distinct cognitive domains in a large cross-sectional, age-restricted and high functioning cohort. These findings emphasize the importance of healthy aging approaches that target both health literacy and lifestyle behaviors to promote functional capacity across the lifespan.

neuroscience↗

bioRxiv2023

Full genome sequence analysis of African swine fever virus isolates from Cameroon

African swine fever is a devastating disease of domestic pigs that has spread across the globe since its introduction into Georgia in 2007. The etiological agent is a large double-stranded DNA virus with a genome of 170 to 180 kb in length depending on the isolate. Much of the differences in genome length between isolates are due to variations in the copy number of five different multigene families that are encoded in repetitive regions that are towards the termini of the covalently closed ends of the genome. Molecular epidemiology of ASFV is primarily based on Sanger sequencing of a few conserved and variable regions, but due to the stability of the dsDNA genome changes in the variable regions occur relatively slowly. Observations in Europe and Asia have shown that changes in other genetic loci can occur and that this could be useful in molecular tracking. ASFV has been circulating in Western Africa for at least forty years. It is therefore reasonable to assume that changes may have accumulated in regions of the genome other than the standard targets over the years. At present only one full genome sequence is available for an isolate from Western Africa, that of a highly virulent isolate collected from Benin during an outbreak in 1997. In Cameroon, ASFV was first reported in 1981 and outbreaks have been reported to the present day and is considered endemic. Here we report three full genome sequences from Cameroon isolates of 1982, 1994 and 2018 outbreaks and identify novel single nucleotide polymorphisms and insertion-deletions that may prove useful for molecular epidemiology studies in Western Africa and beyond.

microbiology↗

bioRxiv2023

Unsupervised identification of internal perceptual states influencing psychomotor performance

AO_SCPLOWBSTRACTC_SCPLOWWhen humans perform repetitive tasks over long periods, their performance is not constant. People may drift in and out of states that might be loosely categorised as engagement, disengagement or flow and these will be reflected in multiple aspects of their performance (for example, reaction time, accuracy, criteria shifts and potentially longer-term strategy) but until recently it has been challenging to relate these behavioural states to the underlying neural mechanisms that generate them. Here, we took Magnetoencephalograpy recordings of participants performing an engaging task that required rapid, strategic behavioural responses. In this way we acquired both high density neural data and contemporaneous, dense behavioural data. Specifically, participants played a laboratory version of Tetris which collects detailed recordings of player input and game-state throughout performance. We asked whether it was possible to infer the presence of distinct behavioural states from the behavioural data and, if so, whether these states would have distinct neural correlates. We used hidden Markov modelling to segment the behavioural time series into states with unique behavioural signatures, finding that we could identify three distinct and robust behavioural states. We then computed occipital alpha power across each state. These within-participant differences in alpha power were statistically significant, suggesting that individuals shift between behaviourally and neurally distinct states during complex performance, and that visuo-spatial attention change across these states.

neuroscience↗

bioRxiv2022

Prevalence and public health significance of Lyssavirus in bats in North region of Cameroon

BackgroundRabies is a zoonotic disease of all warm-blooded animals including humans. Though, there is little knowledge of the status of rabies in wild animals in Cameroon, the disease is endemic in the country with dogs being the main source of transmission. Bat habitats are widespread in Cameroon, but there is little information on the prevalence of rabies-like viruses in bats, nor the role of bats as a potential reservoir of rabies. MethodsA cross sectional study was carried out to determine the prevalence and risk factors of Lyssavirus in bats in the Northern region of Cameroon. A total of 212 bats belonging to three families (Pteropodidae, Vespertilionidae, Molossidae) and 5 species were randomly sampled in 7 localities in the North of Cameroon and were tested for Lyssavirus antigen using direct Immunofluorescence Test (IFA). Overall, 57 (26.89%) of the bats collected showed an IFA positive reaction. The prevalence was higher (P<0.05) in adult bats (33.33%, 95% CI: 25.15 - 42.66) compared to young individuals (20.19%). The main risk factors identified in the study for human exposure to bats were gender (Male), educational level (tertiary), religion (Christianity), ethnic group (Matal), the presence of bats in the area, the practice of bat hunting and consumption and the level of awareness on bat rabies-like viruses. ConclusionThe study found the first evidence of Lyssavirus in bats in Cameroon. This finding revealed that bat rabies-like viruses are real and constitutes a potential human health problem in communities with bat habitats in the North region of Cameroon. Enhancing the level of public awareness and health education on the potential of bats as reservoirs of Lyssavirus in Cameroon as well as the integration of the "One Health" approach for effective management of animal and human rabies should be emphasized. Author summaryRabies is a zoonotic disease caused by a virus of the genus Lyssavirus. It affects all warm-blooded animals including humans. Canine and Human rabies are well documented as endemic in Cameroon, but little is known about this disease in wildlife, in particular among bats, despite their multiple interactions with the inhabitants of Northern Cameroon. Indeed, bats were hunted, sold and eaten as bush meat by local populations. We investigated the presence of Lyssavirus in bat and assessed the risk factors of human exposure to bats in the Northern region of Cameroon. The study highlights that Lyssavirus is present in bats in this area. The population was aware of human and canine rabies, however, the presence of the disease in bats was less known. Based on these findings, investigating bat populations on a large scale, to characterise the Lyssavirus strains circulating in the region, as well as educate the local population on the risks of rabies transmission from bats to humans and other animals.

microbiology↗