Urotensin II (UII) is a potent vasoconstrictor in mammals, but the source of circulating UII remains unclear. Investigations of the caudal neurosecretory system (CNSS), considered the major source of UII in fish, alongside target tissue expression of UII receptor (UT), can provide valuable insights into this highly conserved regulatory system. We report UII gene characterization, expression of the first fish UT, and responses to salinity challenge in flounder. The 12-aa UII peptide shares 73% sequence identity with pig and human UII. Flounder UT receptor shares 56.7% identity with rat. Although the CNSS is the major site of UII expression, RT-PCR revealed expression of UII and UT in all tissues tested. Around 30-40% of large CNSS Dahlgren cells expressed UII, alone or in combination with urotensin I and/or corticotrophin releasing hormone. Immunolocalization of UT in osmoregulatory tissues (gill, kidney) was associated with vascular elements. There were no consistent differences in CNSS UII expression or plasma UII between seawater (SW)- and freshwater (FW)-adapted fish, although gill and kidney UT expression was lower in FW animals. After acute transfer from SW to FW, plasma UII and kidney and gill UT expression were reduced, whereas UT expression in kidney was increased after reverse transfer. UII appears to be more important to combat dehydration and salt-loading in SW than the hemodilution faced in FW. Potentially, altered target tissue sensitivity through changes in UT expression, is an important physiological controlling mechanism, not only relevant for migratory fish but also likely conserved in mammals.
CRH and urotensin I (UI) are neuroendocrine peptides that belong to the superfamily of corticotropin-releasing factors. In mammals, these peptides regulate the stress response and other central nervous system functions, whereas in fish an involvement for UI in osmoregulation has also been suggested. We have identified, characterized, and localized the genes encoding these peptides in a unique fish neuroendocrine organ, the caudal neurosecretory system (CNSS). The CRH and UI precursors, isolated from a European flounder CNSS library, consist of 168 and 147 amino acid residues, respectively, with an overall homology of approximately 50%. Both precursors contain a signal peptide, a divergent cryptic region and a 41-amino acid mature peptide with cleavage and amidation sites. Genomic organization showed that whole CRH and UI coding sequences are contained in a single exon. Northern blot analysis and quantitative PCR of a range of tissues confirmed the CNSS as a major site of expression of both CRH and UI and thus serves as a likely source of circulating peptides. In situ hybridization demonstrated that CRH and UI colocalize to the same cells of the CNSS. Our findings suggest that, in euryhaline fish, the CNSS is a major site of production of CRH and probably contributes to the high circulating levels observed in response to specific environmental challenges. Furthermore, the localization of CRH and UI within the same cell population suggests an early, possibly shared role for these peptides in controlling stress-mediated adaptive plasticity.
In 2010, SRA Direct Instructioni was introduced across the curriculum in two remote Cape York schools, as a key aspect of social and welfare reform. There is national political interest in these reforms, which link welfare policy to State primary school education conceived as basic skills training. Reflecting the political interest, national newspapers ran the story that Direct Instruction had provided almost miraculous results after 17 weeks (Devine 2010a). Alternative approaches to literacy development in Indigenous education did not get the same sort of media attention. Noel Pearson provides the intellectual basis for Cape York social reforms, through his writing, political advocacy and leadership of organisations involved in the reforms. His ultimate goal is successful mainstream education leading to economic integration, where young people are „completely fluent in their own culture and the wider culture‟ (Pearson 2009:57). The question posed by this vision is „What kind of education can produce these flexible, bicultural, working people who keep their traditions alive?‟
Background Recruiting participants to a clinical study is a resource-intensive process with a high failure rate. The Scottish Health Research Register (SHARE) provides recruitment support service which helps researchers recruit participants by searching patients’ Electronic Health Records (EHRs). The current study aims to evaluate the performance of SHARE in participant recruitment. Methods Recruitment projects eligible for evaluation were those that were conducted for clinical trials or observational studies and finished before 2020. For analysis of recruitment data, projects with incomplete data were excluded. For each project we calculated, from SHARE records, 1) the fraction of the participants recruited through SHARE as a percentage of the number requested by researchers (percentage fulfilled), 2) the percentage of the potential candidates provided by SHARE to researchers that were actually recruited (percentage provided and recruited), 3) the percentage of the participants recruited through SHARE of all the potentially eligible candidates identified by searching registrants’ EHRs (percentage identified and recruited). Research teams of the eligible projects were invited to participate in an anonymised online survey. Two metrics were derived from research teams’ responses, including a) the fraction of the recruited over the study target number of participants (percentage fulfilled), and b) the percentage of the participants recruited through SHARE among the candidates received from SHARE (percentage provided and recruited). Results Forty-four projects were eligible for inclusion. Recruitment data for 24 projects were available (20 excluded because of missingness or incompleteness). Survey invites were sent to all the eligible research teams and received 12 responses. Analysis of recruitment data shows the overall percentage fulfilled was 34.2% (interquartile 13.3–45.1%), the percentage provided and recruited 29.3% (interquartile 20.6–52.4%) and percentage identified and recruited 4.9% (interquartile 2.6–10.2%). Based on the data reported by researchers, percentage fulfilled was 31.7% (interquartile 5.8–59.6%) and percentage provided and recruited was 20.2% (interquartile 8.2–31.0%). Conclusions SHARE may be a valuable resource for recruiting participants for some clinical studies. Potential improvements are to expand the registrant base and to incorporate more data generated during patients’ different health care encounters into the candidate-searching step.
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