Neural circuit synaptic connectivities (the connectome) provide the anatomical foundation for our understanding of nematode nervous system function. However, other nonsynaptic routes of communication are known in invertebrates including extrasynaptic volume transmission (EVT), which enables short- and/or long-range communication in the absence of synaptic connections. Although EVT has been highlighted as a facet of Caenorhabditis elegans neurosignaling, no experimental evidence identifies body cavity fluid (pseudocoelomic fluid; PCF) as a vehicle for either neuropeptide or biogenic amine transmission. In the parasitic nematode Ascaris suum, FMRFamide-like peptides encoded on flp-18 potently stimulate female reproductive organs but are expressed in cells that are anatomically distant from the reproductive organ, with no known synaptic connections to this tissue. Here we investigate nonsynaptic neuropeptide signaling in nematodes mediated by the body cavity fluid. Our data show that (i) A. suum PCF (As-PCF) contains a catalog of neuropeptides including FMRFamide-like peptides and neuropeptide-like proteins, (ii) the A. suum FMRFamide-like peptide As-FLP-18A dominates the As-PCF peptidome, (iii) As-PCF potently modulates nematode reproductive muscle function ex vivo, mirroring the effects of synthetic FLP-18 peptides, (iv) As-PCF activates the C. elegans FLP-18 receptors NPR-4 and -5, (v) As-PCF alters C. elegans behavior, and (vi) FLP-18 and FLP-18 receptors display pan-phylum distribution in nematodes. This study provides the first direct experimental evidence to support an extrasynaptic volume route for neuropeptide transmission in nematodes. These data indicate nonsynaptic signaling within the nematode functional connectome and are particularly pertinent to receptor deorphanization approaches underpinning drug discovery programs for nematode pathogens.
Grassroot-led global social movements have become increasingly prominent on mainstream media and political agendas. In Scotland, several of these have resulted in significant policy change, including the period poverty movement, which addresses inequalities relating to menstruation. The chapter looks to this movement as a case study, showing how several interventions have led the country to be hailed a world leader in policies providing free access to menstrual products. It will analyse the conditions under which this movement first took hold in Scotland in 2016, moving chronologically from the first mention of the term "period poverty" in legacy media. It will show how the increasing visibility and discursive realisation, or crystallization, of the term itself fuelled further activism to influence the political agenda. In doing so, it will show the increasingly hybrid and circuitous dynamic of contemporary political communication and how taking a holistic approach to viewing this may give added insight to appraisals of media and political agenda setting.
Much recent research has focussed on the manner in which women political leaders are portrayed in media (Childs, 2008;Campus, 2013;O'Neill and Savigny, 2014). This article examines the press discourses around Scottish Deputy First Minister Nicola Sturgeon, beginning before her participation in the 2004 Scottish National Party (SNP) leadership contest, and continuing through to her appointment as Scottish First Minister in 2014. Starting prior to her deputy leadership, a variety of definitional strategies positioned Sturgeon as aggressive and shrewish. Subsequently, in keeping with the obligations of a more 'intimate' politics, we find a softening and domestication of Sturgeon's media image, alongside discourses of political competence and professionalism. Yet, the article shows how these shifts took place in a manner that continued to call upon established gendered discourses, often with newspapers using tactics of distancing. We suggest this illustrates the competing pulls of media logic, where the mediatisation of Sturgeon's image produces a marketable political persona, but accompanied by those residual gendered discourses long associated with the political press.
Nematode parasites undermine human health and global food security. The frontline anthelmintic portfolio used to treat parasitic nematodes is threatened by the escalation of anthelmintic resistance, resulting in a demand for new drug targets for parasite control. Nematode neuropeptide signalling pathways represent an attractive source of novel drug targets which currently remain unexploited. The complexity of the nematode neuropeptidergic system challenges the discovery of new targets for parasite control, however recent advances in parasite ‘omics’ offers an opportunity for the in silico identification and prioritization of targets to seed anthelmintic discovery pipelines. In this study we employed Hidden Markov Model-based searches to identify ~1059 Caenorhabditis elegans neuropeptide G-protein coupled receptor (Ce-NP-GPCR) encoding gene homologs in the predicted protein datasets of 10 key parasitic nematodes that span several phylogenetic clades and lifestyles. We show that, whilst parasitic nematodes possess a reduced complement of Ce-NP-GPCRs, several receptors are broadly conserved across nematode species. To prioritize the most appealing parasitic nematode NP-GPCR anthelmintic targets, we developed a novel in silico nematode parasite drug target prioritization pipeline that incorporates pan-phylum NP-GPCR conservation, C. elegans-derived reverse genetics phenotype, and parasite life-stage specific expression datasets. Several NP-GPCRs emerge as the most attractive anthelmintic targets for broad spectrum nematode parasite control. Our analyses have also identified the most appropriate targets for species- and life stage- directed chemotherapies; in this context we have identified several NP-GPCRs with macrofilaricidal potential. These data focus functional validation efforts towards the most appealing NP-GPCR targets and, in addition, the prioritization strategy employed here provides a blueprint for parasitic nematode target selection beyond NP-GPCRs.
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