Detection of Galba truncatula, Fasciola hepatica and Calicophoron daubneyi environmental DNA within water sources on pasture land, a future tool for fluke control?

Abstract Background: Increasing trematode prevalence and disease occurrence in livestock is a major concern. With the global spread of anthelmintic resistant trematodes, future control strategies must incorporate approaches focusing on avoidance of infection. The reliance of trematodes on intermediate snail hosts to successfully complete their life-cycle means livestock infections are linked to the availability of respective snail populations. By identifying intermediate snail host habitats, infection risk models may be strengthened whilst farmers may confidently apply pasture management strategies to disrupt the trematode life-cycle. However, accurately identifying and mapping these risk areas is challenging. Methods: In this study, environmental DNA (eDNA) assays were designed to reveal Galba truncatula, Fasciola hepatica and Calicophoron daubneyi presence within water sources on pasture land. eDNA was captured using a filter-based protocol, with DNA extracted using the DNeasy? PowerSoil? kit and amplified via PCR. In total, 19 potential G. truncatula habitats were analysed on four farms grazed by livestock infected with both F. hepatica and C. daubneyi. Results: Galba truncatula eDNA was identified in 10/10 habitats where the snail was detected by eye. Galba truncatula eDNA was also identified in four further habitats where the snail was not physically detected. Fasciola hepatica and C. daubneyi eDNA was also identified in 5/19 and 8/19 habitats, respectively. Conclusions: This study demonstrated that eDNA assays have the capabilities of detecting G. truncatula, F. hepatica and C. daubneyi DNA in the environment. Further assay development will be required for a field test capable of identifying and quantifying F. hepatica and C. daubneyi infection risk areas, to support future control strategies. An eDNA test would also be a powerful new tool for epidemiological investigations of parasite infections on farms.publishersversionPeer reviewe

Phage-assisted continuous evolution of proteases with altered substrate specificity

Here we perform phage-assisted continuous evolution (PACE) of TEV protease, which canonically cleaves ENLYFQS, to cleave a very different target sequence, HPLVGHM, that is present in human IL-23. A protease emerging from ∼2500 generations of PACE contains 20 non-silent mutations, cleaves human IL-23 at the target peptide bond, and when pre-mixed with IL-23 in primary cultures of murine splenocytes inhibits IL-23-mediated immune signaling. We characterize the substrate specificity of this evolved enzyme, revealing shifted and broadened specificity changes at the six positions in which the target amino acid sequence differed. Mutational dissection and additional protease specificity profiling reveal the molecular basis of some of these changes. This work establishes the capability of changing the substrate specificity of a protease at many positions in a practical time scale and provides a foundation for the development of custom proteases that catalytically alter or destroy target proteins for biotechnological and therapeutic applications

The Importance of Incorporating Technological Advancements into the Prosthetic Eye Development: A Perspective Commentary

Application of technology into healthcare has typically been targeted to high demand illnesses and treatments. However, with an increasing need to meet patient’s expectations combined with increased accessibility and reduced costs, smaller healthcare fields are starting to investigate its function and usability. Services have historically been led by skills and expertise, and recent developments are being seen by ocularists in the field of prosthetic eyes who acknowledge the potential benefit from technological advancement. Utilising the technologies recently investigated in maxillofacial prosthesis can start the evolutionary process where products are continually re-designed and re-developed to achieve excellent patient outcome and satisfaction levels

Connecting ecosystem services research and human rights to revamp the application of the precautionary principle

With ecosystem services (ES) vital for human wellbeing1, the protection of nature is a human rights matter. We outline how recent advances in international human rights law should inform a revamp of how precaution is applied within environmental decision-making. Critically, precautionary decision-making must evolve to make use of best-available evidence, including novel ES research approaches, to assess ‘foreseeable’ harms to all aspects of human wellbeing that are protected as human rights

Questionnaire study to gain an insight into the manufacturing and fitting process of artificial eyes in children: an ocularist perspective

Purpose To gain an insight into the manufacturing and fitting of artificial eyes in children and potential improvements to the process. Method An online qualitative survey was distributed to 39 ocularists/prosthetists in Europe and Canada. Participants were recruited through purposive sampling, specifically maximum variation sampling from the researcher’s contacts and an online search. Results The findings highlighted the current impression technique as being the most difficult yet most important part of the current process for both the ocularist and child patient. Negatively affecting obtaining a good impression, the child patients distress can be reduced by their parents by providing encouragement, reassurance, practicing the insertion and removal of the artificial eye and being matter of fact. Whilst improvements to the current process provided mixed views, the incorporation of current technology was perceived as not being able to meet the requirements to produce aesthetically pleasing artificial eyes. Conclusion The current artificial eye process can be seen as an interaction with its success being dependent on the child patient’s acceptance and adjustment which is dependent on the factors associated to the process. Investigation into the needs of the patient and whether technology can improve the process are the next steps in its advancement

Improving the DNA specificity and applicability of base editing through protein engineering and protein delivery

We recently developed base editing, a genome-editing approach that enables the programmable conversion of one base pair into another without double-stranded DNA cleavage, excess stochastic insertions and deletions, or dependence on homology-directed repair. The application of base editing is limited by off-target activity and reliance on intracellular DNA delivery. Here we describe two advances that address these limitations. First, we greatly reduce off-target base editing by installing mutations into our third-generation base editor (BE3) to generate a high-fidelity base editor (HF-BE3). Next, we purify and deliver BE3 and HF-BE3 as ribonucleoprotein (RNP) complexes into mammalian cells, establishing DNA-free base editing. RNP delivery of BE3 confers higher specificity even than plasmid transfection of HF-BE3, while maintaining comparable on-target editing levels. Finally, we apply these advances to deliver BE3 RNPs into both zebrafish embryos and the inner ear of live mice to achieve specific, DNA-free base editing in vivo

Addressing the ocean-climate nexus in the BBNJ agreement : strategic environmental assessments, human rights and equity in ocean science

The Agreement on Marine Biodiversity of Areas beyond National Jurisdiction (BBNJ Agreement) opens a new path in international law towards addressing issues at the ocean-climate nexus, as well as considering implications for the protection of human rights and achieving equity among States in the context of ocean knowledge production and environmental management. Based on an interdisciplinary reflection, the new international obligations on strategic environmental assessments (SEAs), and new institutional arrangements, are identified as crucial avenues to addressing climate change mitigation and ensuring fair research partnerships, mutual capacity-building and technology co-development between the Global North and South. SEAs can also support integrated implementation of other parts of the BBNJ Agreement and contribute to the broader effectiveness of the general provisions of the United Nations Convention on the Law of the Sea on the protection of the marine environment, within and beyond national jurisdiction

Trait impulsivity in Juvenile Myoclonic Epilepsy

Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta‐analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) moderated by specific seizure characteristics; and (iii) associated with psychiatric adverse effects of antiepileptic drugs (AEDs)

Punishment in the Frame: Rethinking the History and Sociology of Art

Images of punishment have featured prominently in Western art and this article explores what might be learnt from studying such pictures of suffering. It seeks to develop an approach to the visual that avoids both the essentialism of art history and the reductionism of sociology by offering a rethinking of the relationships between the two. It begins by setting out the current state of the sociology of art, before discussing ‘new’ art histories that are inspired by social analysis. It then concentrates on how images of punishment have featured in Western art. This substantive material provides a rich resource to understand the force of representation and offers an opportunity to develop an aesthetic sociology that avoids some of the problems identified in the article. The approach developed in the second part is one that seeks to elaborate an aesthetic sociology that combines a historical sensitivity to images with the analytical concerns of social science. It strives to extend the art historian Michael Baxandall’s writings toward more sociological interpretations of visual analysis