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Horton, D.

Publications and source records attributed to Horton, D..

4 recordsLinked to original sources

Sensitivity analysis of factors influencing the ecology of mosquitoes involved in the transmission Rift Valley fever virus transmission

Vector-borne diseases are a major global health concern, with Rift Valley fever (RVF) serving as a key example due to its impact on both human and animal health. Predicting and controlling such diseases requires understanding how environmental factors shape mosquito ecology. Due to mosquito abundance, distribution, and behavior being influenced by ecological conditions, identifying the drivers of these dynamics is essential for anticipating transmission risk. This study aims to assess the sensitivity of ecological factors governing the ecology of mosquitoes, using a deterministic, compartmental model of RVF transmission in Kenya. We conducted a local and global sensitivity analysis on ten model parameters: four species-specific parameters for each of the two mosquito species of interest (Culex spp. and Aedes spp.) and two parameters shared across species. The focal species-specific parameters were the area scanned before oviposition, the proportion of area suitable for egg laying, the number of eggs laid, and the maximum density of eggs. The two shared parameters represented livestock population size and the influence of livestock on vector fecundity and gonotrophic cycles. Parameter ranges and distributions were defined using a scoping literature review. Sobol sensitivity analysis was performed under two environmental scenarios: (i) constant temperature and water body area, and (ii) periodically varying temperature and water body area, implemented using a time-dependent Sobol framework. Results revealed species-specific differences in parameter influence. For Culex spp., uncertainty in the area scanned for oviposition was highly influential, while for Aedes spp., the pairing of the proportion of area that eggs are laid on and the maximum density of eggs emerged as dominant. These findings highlights the need for improved empirical data on spatial oviposition patterns across water bodies, as current evidence remains limited. By identifying the ecological parameters that most critically shape mosquito population dynamics and/or influence model outputs, and thereby the transmission potential of RVF, this work supports more targeted vector surveillance and strengthens public health decision-making in RVF-endemic regions. Author summaryRift Valley fever is a disease spread by mosquitoes that affects both people and animals. Understanding what drives mosquito populations can help us predict and control the spread of Rift Valley fever. In this study, we used a published mathematical model to conduct a sensitivity analysis to explore how different parameters within the model affect mosquito numbers. In total, we investigated ten parameters, where the analysis emphasizes the role of water bodies used by mosquitoes to lay their eggs. We found that this factor plays a major role in how many mosquitoes are present. However, there is still a lot we do not know about exactly where mosquitoes choose to lay their eggs. More research in this area could improve how we predict and manage Rift Valley fever and other mosquito-borne diseases outbreaks. Our findings highlight which environmental details matter most, and they can help guide better strategies for mosquito control and disease prevention.

ecology↗

PIWI silencing mechanism involving the retrotransposon nimbus orchestrates resistance to infection with Schistosoma mansoni in the snail vector, Biomphalaria glabrata

BackgroundSchistosomiasis remains widespread in many regions despite efforts at its elimination. By examining changes in the transcriptome at the host-pathogen interface in the snail Biomphalaria glabrata and the blood fluke Schistosoma mansoni, we previously demonstrated that an early stress response in juvenile snails, manifested by induction of heat shock protein 70 (Hsp 70) and Hsp 90 and of the reverse transcriptase (RT) domain of the B. glabrata non-LTR-retrotransposon, nimbus, were critical for B. glabrata susceptibility to S. mansoni. Subsequently, juvenile B. glabrata BS90 snails, resistant to S. mansoni at 25{degrees}C become susceptible by the F2 generation when maintained at 32{degrees}C, indicating an epigenetic response. Methodology/Principal FindingsTo better understand this plasticity in susceptibility of the BS90 snail, mRNA sequences were examined from S. mansoni exposed juvenile BS90 snails cultured either at 25{degrees}C (permissive temperature) or 32{degrees}C (non-permissive). Comparative analysis of transcriptomes from snails cultured at the non-permissive and permissive temperatures revealed that whereas stress related transcripts dominated the transcriptome of susceptible BS90 juvenile snails at 32{degrees}C, transcripts encoding proteins with a role in epigenetics, such as PIWI (BgPiwi), chromobox protein homolog 1 (BgCBx1), histone acetyl transferase histone deacetylase (HDAC) and metallotransferase (MT) were highly expressed in those cultured at 25{degrees}C. To further determine a role for BgPiwi in B. glabrata susceptibility to S. mansoni, siRNA corresponding to the BgPiwi encoding transcript was utilized to suppress expression of BgPiwi, rendering the resistant BS90 juvenile snail susceptible to infection at 25{degrees}C. Given transposon silencing activity of PIWI as a facet of its role as guardian of the integrity of the genome, we examined the expression of the nimbus RT encoding transcript at 120 min after infection of resistant BS90 piwi-siRNA treated snails. We observed that nimbus RT was upregulated, indicating that modulation of the transcription of the nimbus RT was associated with susceptibility to S. mansoni in BgPiwi- siRNA treated BS90 snails. Furthermore, treatment of susceptible snails with the RT inhibitor lamivudine, before exposure to S. mansoni, blocked S. mansoni infection concurrent with downregulation of the nimbus RT transcript and upregulation of the BgPiwi encoding transcript in the lamivudine-treated, schistosome-exposed susceptible snails. Conclusions and SignificanceThese findings support a role for the interplay of BgPiwi and nimbus in the epigenetic modulation of plasticity of resistance/susceptibility in the snail-schistosome relationship.

molecular biology↗

Survival and development of potato psyllid (Hemiptera: Triozidae) on Convolvulaceae: effects of a plant-fungus symbiosis (Periglandula)

Plant species in the family Solanaceae are the usual hosts of potato psyllid, Bactericera cockerelli ([S]ulc) (Hemiptera: Psylloidea: Triozidae). However, the psyllid has also been shown to develop on some species of Convolvulaceae (bindweeds and morning glories). Developmental success on Convolvulaceae is surprising given the rarity of psyllid species worldwide associated with this plant family. We assayed 14 species of Convolvulaceae across four genera (Convolvulus, Calystegia, Ipomoea, Turbina) to identify species that allow development of potato psyllid. Two populations of psyllids were assayed (Texas, Washington). The Texas population overlaps extensively with native Convolvulaceae, whereas Washington State is noticeably lacking in Convolvulaceae. Results of assays were overlain on a phylogenetic analysis of plant species to examine whether Convolvulaceae distantly related to the typical host (potato) were less likely to allow development than species of Convolvulaceae more closely related. Survival was independent of psyllid population and location of the plant species on our phylogenetic tree. We then examined whether presence of a fungal symbiont of Convolvulaceae (Periglandula spp.) affected psyllid survival. These fungi associate with Convolvulaceae and produce a class of mycotoxins (ergot alkaloids) that may confer protection against plant-feeding arthropods. Periglandula was found in 11 of our 14 species, including in two genera (Convolvulus, Calystegia) not previously known to host the symbiont. Of these 11 species, leaf tissues from five contained large quantities of two classes of ergot alkaloids (clavines, amides of lysergic acid) when evaluated by LC-MS/MS. All five species also harbored Periglandula. No ergot alkaloids were detected in species free of the fungal symbiont. Potato psyllid rapidly died on species found to harbor Periglandula and fungus-produced alkaloids, but survived on species in which the mutualism was absent. These results support the hypothesis that a plant-fungus symbiotic relationship affects the suitability of certain Convolvulaceae to potato psyllid.

ecology↗

Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies.

Rabies viruses have the highest case fatality rate of any known virus and are responsible for an estimated 60,000 deaths each year. This is despite the fact that there are highly efficacious vaccines and postexposure prophylaxis available. However, while it is assumed these biologics provide protection against all rabies virus isolates, there are certain subdivisions of RABV lineages, such as within the Arctic-like RABV (AL rabies virus lineage, where data is limited and thus the potency of existing biologics has not been thoroughly assessed. By fusing the Arctic-like rabies virus envelope glycoprotein ecto- and transmembrane domains with the vesicular stomatitis virus cytoplasmic domain, a high titre (7.7 x 105 - 6.1 x 106 RLU/ml) pseudotyped virus was generated that was subsequently used in a pseudotyped virus neutralisation assay. These results showed that Arctic-like rabies viruses are neutralised to human, canine and feline vaccines and human post-exposure prophylaxis and this was not influenced by the swapping of the cytoplasmic domains (CVS-11 vs CVS-11etmVSVc; r = 0.99, p < 0.0001). This study supports the concept that rabies virus vaccines and newly identified mAbs are able to neutralise rabies virus variants that cluster in a monophyletic clade, referred to as phylogroup I lyssaviruses.

microbiology↗