Ovine psoroptic mange (sheep scab) is an infectious condition caused by an allergen-induced hypersensitivity response to the mite Psoroptes ovis. Infestation results in clinical disease, economic ...loss and welfare issues in many sheep-producing countries. The aim of this study was to compare the prevalence and spatial pattern of sheep scab on contiguous farms, using both self-reported clinical outbreak history (2012-2020) and serological testing with an enzyme-linked immunosorbent assay (2021/2022). Farms included in the study were located in three regions of known high scab prevalence in North, Central and Southwest England. In total, 254 farms completed both a questionnaire, which provided the clinical scab history of the farm, and submitted results of serological testing with the ELISA. A scab outbreak was reported by 17.4% (+ or - confidence interval CI: 4.6%; n = 48) of farms in 2020 based on clinical diagnosis; scab was diagnosed by the ELISA on 25.6% (+ or - 5.5%; n = 65) of farms in 2021/2022. Comparison of self-reported clinical scab cases with the ELISA test results identified a group of farms (n = 52) that did not report scab in 2020, or in some cases did not report having scab over the previous 8 years (n = 20), but whose flocks were nevertheless seropositive in 2021/2022. A small number of flocks, particularly those using common grazings in North England, where handling is infrequent, often comprising less susceptible sheep breeds, may have persistent scab infestations that are generally undetected by clinical inspection. The data highlight the advantages of serological testing to identify exposure to scab in flocks where clinical signs are less easily detected.
An emerging approach with potential in improving the treatment of neurodegenerative diseases and brain tumors is the use of focused ultrasound (FUS) to bypass the blood-brain barrier (BBB) in a ...non-invasive and localized manner. A large body of pre-clinical work has paved the way for the gradual clinical implementation of FUS-induced BBB opening. Even though the safety profile of FUS treatments in rodents has been extensively studied, the histological and behavioral effects of clinically relevant BBB opening in large animals are relatively understudied. Here, we examine the histological and behavioral safety profile following localized BBB opening in non-human primates (NHPs), using a neuronavigation-guided clinical system prototype. We show that FUS treatment triggers a short-lived immune response within the targeted region without exacerbating the touch accuracy or reaction time in visual-motor cognitive tasks. Our experiments were designed using a multiple-case-study approach, in order to maximize the acquired data and support translation of the FUS system into human studies. Four NHPs underwent a single session of FUS-mediated BBB opening in the prefrontal cortex. Two NHPs were treated bilaterally at different pressures, sacrificed on day 2 and 18 post-FUS, respectively, and their brains were histologically processed. In separate experiments, two NHPs that were earlier trained in a behavioral task were exposed to FUS unilaterally, and their performance was tracked for at least 3 weeks after BBB opening. An increased microglia density around blood vessels was detected on day 2, but was resolved by day 18. We also detected signs of enhanced immature neuron presence within areas that underwent BBB opening, compared to regions with an intact BBB, confirming previous rodent studies. Logistic regression analysis showed that the NHP cognitive performance did not deteriorate following BBB opening. These preliminary results demonstrate that neuronavigation-guided FUS with a single-element transducer is a non-invasive method capable of reversibly opening the BBB, without substantial histological or behavioral impact in an animal model closely resembling humans. Future work should confirm the observations of this multiple-case-study work across animals, species and tasks.
Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of ...monoclonal antibodies (mAb) in preventing symptomatic SARS-CoV-2 infection. We use data on the in vivo concentration of mAb and the associated protection from COVID-19 over time to model the dose-response relationship of mAb for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a mAb concentration of 96-fold of the in vitro IC50 (95% CI: 32-285). This relationship provides a tool for predicting the prophylactic efficacy of new mAb and against SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either mAb treatment or vaccination. We find no significant difference between the 50% protective titer for mAb and vaccination, although sample sizes limited the power to detect a difference.
Aim: Cryptic species in the Neofusicoccum parvum—N. ribis species complex have only recently been described, invalidating previous interpretations on host and geographical distribution. This study ...aimed to characterize the diversity and distribution of these species and to understand the patterns of host association, likely origins and their patterns of spread. Location: Australia, Brazil, Cameroon, Chile, China, Colombia, Ethiopia, France, Greece, India, Indonesia, Iran, Italy, Japan, Kenya, Mexico, New Zealand, Panama, Portugal, Puerto Rico, South Africa, South Korea, Spain, Swaziland, Taiwan, Thailand, Uganda, United States of America, Uruguay, Zambia and Zimbabwe. Methods: Using the unique polymorphisms that separate species within the complex, we evaluated sequence search results available in public and in our own databases. In addition, the global distribution of diversity of N. parvum was analysed using seven microsatellite markers. Results: Neofusicoccum parvum is found in 90 hosts across six continents and 29 countries. Neofusicoccum kwambonambiense is found on four continents, six countries and on 14 hosts; N. occulatum is found on four continents, four countries and on 11 hosts; N. umdonicola is found on two continents, countries and hosts; N. cordaticola is found on three continents, countries and hosts; N. batangarum is found on two continents, three countries and three hosts; and N. ribis is found on one host in one country. Population genetic analysis of the global N. parvum population reflects admixture and repeat introductions. Main conclusions: This study illustrates the unfettered and frequent movement of latent pathogens across international borders. Amongst the species in the N. parvum—N. ribis complex, N. parvum is the most widespread and has been reported on the majority of the hosts studied. The current dispersal of N. parvum and its sister species is probably due to repeated introductions of plant material into new growing areas, with Eucalyptus and Vitis vinifera being two prominent candidates for material transfer.
Many members of the Oomycota genus Phytophthora cause economic and environmental impact diseases in nurseries, horticulture, forest, and natural ecosystems and many are of regulatory concern around ...the world. At present, there are 223 described species, including eight unculturable and three lost species. Twenty-eight species need to be redescribed or validated. A lectotype, epitype or neotype was selected for 20 species, and a redescription based on the morphological/molecular characters and phylogenetic placement is provided. In addition, the names of five species are validated: P. cajani , P. honggalleglyana (Synonym: P. hydropathica ), P. megakarya , P. pisi and P. pseudopolonica for which morphology and phylogeny are given. Two species, P. ×multiformis and P. uniformis are presented as new combinations. Phytophthora palmivora is treated with a representative strain as both lecto- and epitypification are pending. This manuscript provides the updated multigene phylogeny and molecular toolbox with seven genes (ITS rDNA, β-tub , COI , EF1α , HSP90 , L10 , and YPT1 ) generated from the type specimens of 212 validly published, and culturable species (including nine hybrid taxa). The genome information of 23 types published to date is also included. Several aspects of the taxonomic revision and phylogenetic re-evaluation of the genus including species concepts, concept and position of the phylogenetic clades recognized within Phytophthora are discussed. Some of the contents of this manuscript, including factsheets for the 212 species, are associated with the “ IDphy : molecular and morphological identification of Phytophthora based on the types” online resource (https://idtools.org/tools/1056/index.cfm). The first version of the IDphy online resource released to the public in September 2019 contained 161 species. In conjunction with this publication, we are updating the IDphy online resource to version 2 to include the 51 species recently described. The current status of the 223 described species is provided along with information on type specimens with details of the host (substrate), location, year of collection and publications. Additional information is provided regarding the ex-type culture(s) for the 212 valid culturable species and the diagnostic molecular toolbox with seven genes that includes the two metabarcoding genes (ITS and COI ) that are important for Sanger sequencing and also very valuable Molecular Operational Taxonomic Units (MOTU) for second and third generation metabarcoding High-throughput sequencing (HTS) technologies. The IDphy online resource will continue to be updated annually to include new descriptions. This manuscript in conjunction with IDphy represents a monographic study and the most updated revision of the taxonomy and phylogeny of Phytophthora , widely considered one of the most important genera of plant pathogens.
The DNA repair capacity of human cells declines with age, in a process that is not clearly understood. Mutation of the nuclear envelope protein barrier-to-autointegration factor 1 (Banf1) has ...previously been shown to cause a human progeroid disorder, Néstor-Guillermo progeria syndrome (NGPS). The underlying links between Banf1, DNA repair and the ageing process are unknown. Here, we report that Banf1 controls the DNA damage response to oxidative stress via regulation of poly ADP-ribose polymerase 1 (PARP1). Specifically, oxidative lesions promote direct binding of Banf1 to PARP1, a critical NAD
-dependent DNA repair protein, leading to inhibition of PARP1 auto-ADP-ribosylation and defective repair of oxidative lesions, in cells with increased Banf1. Consistent with this, cells from patients with NGPS have defective PARP1 activity and impaired repair of oxidative lesions. These data support a model whereby Banf1 is crucial to reset oxidative-stress-induced PARP1 activity. Together, these data offer insight into Banf1-regulated, PARP1-directed repair of oxidative lesions.
The blood feeding poultry red mite (PRM), Dermanyssus gallinae, causes substantial economic damage to the egg laying industry worldwide, and is a serious welfare concern for laying hens and poultry ...house workers. In this study we have investigated the temporal gene expression across the 6 stages/sexes (egg, larvae, protonymph and deutonymph, adult male and adult female) of this neglected parasite in order to understand the temporal expression associated with development, parasitic lifestyle, reproduction and allergen expression.
RNA-seq transcript data for the 6 stages were mapped to the PRM genome creating a publicly available gene expression atlas (on the OrcAE platform in conjunction with the PRM genome). Network analysis and clustering of stage-enriched gene expression in PRM resulted in 17 superclusters with stage-specific or multi-stage expression profiles. The 6 stage specific superclusters were clearly demarked from each other and the adult female supercluster contained the most stage specific transcripts (2725), whilst the protonymph supercluster the fewest (165). Fifteen pairwise comparisons performed between the different stages resulted in a total of 6025 Differentially Expressed Genes (DEGs) (P > 0.99). These data were evaluated alongside a Venn/Euler analysis of the top 100 most abundant genes in each stage. An expanded set of cuticle proteins and enzymes (chitinase and metallocarboxypeptidases) were identified in larvae and underpin cuticle formation and ecdysis to the protonymph stage. Two mucin/peritrophic-A salivary proteins (DEGAL6771g00070, DEGAL6824g00220) were highly expressed in the blood-feeding stages, indicating peritrophic membrane formation during feeding. Reproduction-associated vitellogenins were the most abundant transcripts in adult females whilst, in adult males, an expanded set of serine and cysteine proteinases and an epididymal protein (DEGAL6668g00010) were highly abundant. Assessment of the expression patterns of putative homologues of 32 allergen groups from house dust mites indicated a bias in their expression towards the non-feeding larval stage of PRM.
This study is the first evaluation of temporal gene expression across all stages of PRM and has provided insight into developmental, feeding, reproduction and survival strategies employed by this mite. The publicly available PRM resource on OrcAE offers a valuable tool for researchers investigating the biology and novel interventions of this parasite.
Sheep scab, caused by infestation with the ectoparasitic mite
, is an endemic disease in the Northern Ireland (NI) sheep flock and constitutes significant economic and welfare burdens for the NI ...farming industry. Despite its endemic nature, historically, little research has been undertaken to support the control of the disease in NI. This study offers the first attempt to analyse the psychological and behavioural factors influencing farmers' intentions to implement effective sheep scab control measures in NI. To achieve our objective, quantitative data from a sample of 126 sheep farmers were statistically analysed using an extended theory of planned behaviour approach in an ordered logistic regression modelling framework. Our analyses showed that sheep scab remains an issue of concern in Northern Ireland. The attitudes of the farmers, as well as perceived behavioural control, emotional effect, membership of Business Development Groups (BDGs), and higher education qualifications, were found to be statistically significant factors influencing farmers' intentions to adopt sheep scab control measures. This study provides a solid foundation for how to promote behavioural changes among sheep farmers to improve their ability to implement effective disease control measures, helping to tackle this challenging disease in a more sustainable way in the future.
•Teratosphaeria leaf blight (TLB), caused by six related species, is the most serious leaf disease of plantation Eucalyptus.•Recently, T. destructans has spread from south-east Asia to South Africa ...and T. pseudoeucalypti from Australia to South America.•Management of TLB will involve breeding and selection of tolerant/resistant clones, matching species to site and conditionsoptimal growth in order to reduce stress related disease impacts.•Of paramount concern is the need for more sophisticated and stringent biosecurity measures to reduce the introduction of new pathogens and pathotypes.
In Australia, during the course of the last two decades, plantation area of Eucalyptus has expanded dramatically. One of the most important threats to these trees, and to the forest industries they sustain, is a complex of fungal diseases broadly treated as Teratosphaeria Leaf Blight. The aim of this review is to summarise some of the most important findings relating to Teratosphaeria spp. (previously Kirramyces) associated with leaf and shoot blight of Eucalyptus. The review spans a period of 23 years since the description of the aptly named Teratosphaeria destructans. Six species of Teratosphaeria are associated with leaf and shoot blights of Eucalyptus and these are T. destructans, T. eucalypti, T. novaehollandiae, T. pseudoeucalypti, T. viscida and T. tiwiana. With the exception of T. destructans, all of these species have been found in Australia. Based on the damage they cause, the most significant of these fungi are T. destructans, T. pseudoeucalypti and T. viscida. Teratosphaeria viscida has been found only in the tropics of eastern Australia, while T. destructans and T. pseudoeucalypti have spread globally; T. destructans throughout Asia and South Africa and T. pseudoeucalypti into South America. Factors driving the development of these diseases have included the establishment of plantations adjacent to native eucalypt forests in Australia and planting on sites not favourable to the growth of the host trees. These factors, in conjunction with a lack of selection for resistance to emerging pathogens, lack of resilience to disease in monocultures, and the movement of pathogens with planting stock and seeds around the globe have led to substantial losses. Based on the Teratosphaeria leaf blight example, it is clear that more effective forest management and more stringent biosecurity measurements will be a required to sustain eucalypt plantations globally.
Psoroptic mange, caused by infestation with the ectoparasitic mite, Psoroptes ovis, is highly contagious, resulting in intense pruritus and represents a major welfare and economic concern for the ...livestock industry Worldwide. Control relies on injectable endectocides and organophosphate dips, but concerns over residues, environmental contamination, and the development of resistance threaten the sustainability of this approach, highlighting interest in alternative control methods. However, development of vaccines and identification of chemotherapeutic targets is hampered by the lack of P. ovis transcriptomic and genomic resources.
Building on the recent publication of the P. ovis draft genome, here we present a genomic analysis and transcriptomic atlas of gene expression in P. ovis revealing feeding- and stage-specific patterns of gene expression, including novel multigene families and allergens. Network-based clustering revealed 14 gene clusters demonstrating either single- or multi-stage specific gene expression patterns, with 3075 female-specific, 890 male-specific and 112, 217 and 526 transcripts showing larval, protonymph and tritonymph specific-expression, respectively. Detailed analysis of P. ovis allergens revealed stage-specific patterns of allergen gene expression, many of which were also enriched in "fed" mites and tritonymphs, highlighting an important feeding-related allergenicity in this developmental stage. Pair-wise analysis of differential expression between life-cycle stages identified patterns of sex-biased gene expression and also identified novel P. ovis multigene families including known allergens and novel genes with high levels of stage-specific expression.
The genomic and transcriptomic atlas described here represents a unique resource for the acarid-research community, whilst the OrcAE platform makes this freely available, facilitating further community-led curation of the draft P. ovis genome.