During infection of their human definitive host, schistosomes transform rapidly from free-swimming infective cercariae in freshwater to endoparasitic schistosomules. The ‘somules’ next migrate within the skin to access the vasculature and are surrounded by host molecules that might activate intracellular pathways that influence somule survival, development and/or behaviour. However, such ‘transactivation’ by host factors in schistosomes is not well defined. In the present study, we have characterized and functionally localized the dynamics of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) activation during early somule development in vitro and demonstrate activation of these protein kinases by human epidermal growth factor, insulin, and insulin-like growth factor I, particularly at the parasite surface. Further, we provide evidence that support the existence of specialized signalling domains called lipid rafts in schistosomes and propose that correct signalling to ERK requires proper raft organization. Finally, we show that modulation of PKC and ERK activities in somules affects motility and reduces somule survival. Thus, PKC and ERK are important mediators of host-ligand regulated transactivation events in schistosomes, and represent potential targets for anti-schistosome therapy aimed at reducing parasite survival in the human host.

AS (2016) Inversion of correia repeat enclosed elements in 'Neisseria gonorrhoeae', which will be published in final form at http://dx.doi.org/10.1099/mic.0.000394. This article may be used for non-commercial purposes in accordance with the publisher restrictions. Title:Inversion of Correia Repeat Enclosed Elements in Neisseria gonorrhoeae. Authors:Firat Elbeyioglu*, Sabrina B. Roberts*, Russell Spencer-Smith^, Madhuri Pulijala, Marta A. Zelewska, Jean-Christophe Nebel ‡ , and Lori A. S. Snyder † Affiliations:School of Life Sciences, Pharmacy, and Chemistry, Kingston University, Kingston upon Thames, UK. KT1 Short title:Invertible elements in Neisseria gonorrhoeae. Keywords:Gonococcus; phase variation; inversion; Correia Repeat Enclosed Elements; CREE Subject category:Genomics and systems biology. Word count: 2,652 Depositories:The GenBank accession numbers for the re-sequencing data of Neisseria gonorrhoeae strain NCCP11945 are SRR3547950 and (submitted SUB2025235). Abbreviations: CREE: Correia Repeat Enclosed Element Abstract:Neisseria gonorrhoeae is capable of causing gonorrhoea and more complex diseases in the human host. Within the gonococcal genome are over 100 copies of the IS-like Correia Repeat Enclosed Element, which has been predicted to be mobile within the neisserial genomes. Although there is evidence of ancestral movement of these elements, no previous study has provided evidence for current mobilisation.The Correia Repeat Enclosed Element has the ability to alter gene expression and regulation in many ways: by insertional mutagenesis; by introducing promoter elements; by generating mRNA processing sites, and by association with ncRNAs.Previous studies have compared the genomic locations of Correia Repeat Enclosed Elements in the Neisseria spp., demonstrating that otherwise identical regions have either the element or the target TA insertion site. In this study, we report for the first time movement of Correia Repeat Enclosed Elements, through inversion of the element at its chromosomal location. Analysis of Ion Torrent generated genome sequence data from Neisseria gonorrhoeae strain NCCP11945 passaged for 8 weeks in the laboratory under standard conditions and stress conditions revealed a total of 37 inversions: 24 were exclusively seen in the stressed sample; 7 in the control sample; and the remaining 3 were seen in both samples. These inversions have the capability to alter gene expression in N. gonorrhoeae through the previously determined activities of the sequence features of these elements, potentially resulting in reversible phase variable gene expression. Introduction: