Revisiting the evolution of the somatostatin family: already five genes in the gnathostome ancestor

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Somatostatin 4 regulates growth and modulates gametogenesis in zebrafish

Somatostatin (SST) plays important roles in growth and development. In teleost fishes six SST encoding genes (sst1 to sst6) have been identified although few studies have addressed their function. Here we aim to determine the function of the teleost specific sst4 in the zebrafish. A CRISPR/Cas9 sst4 zebrafish mutant with loss of function (sst4−/−) was produced which grew significantly faster and was heavier at the onset of gonadal maturation than the wild type (WT). Consistent with their faster growth, liver igf1, igf2a and igf2b expression was significantly upregulated in the sst4−/− fish compared to the WT. Histological examination of the ovaries and testis indicated that sst4−/− fish had slightly delayed testicular gametogenesis compared to the WT. Significantly lower expression of igf3, amh, insl3, hsd17b3, hsd11b2, hsd20b, cyp11b and cyp17 was consistently observed in the sst4−/− testis. In contrast, the ovaries had lower expression of igf1, igf2a and cyp19a1a but increased expression of igf2b and hsd20b. The gonadotrophin beta subunits (fshb and lhb) in the brain were downregulated indicating the brain-pituitary-gonadal axis was downregulated in the sst4−/− fish and suggesting that the steroid production is compromised in the maturing gonads. In addition, analysis of sst1 and sst3 mRNA levels in sst4−/− fish suggests a dosage compensation effect of sst1 in the brain and liver. Altogether, the results from the zebrafish sst4−/− line support the idea that sst4 is involved in the regulation of igf signalling, somatic growth and reproduction since steroidogenesis and gametogenesis at pubertal onset were compromised.This research was supported by institutional funds from Shanghai Ocean University and Portuguese national funds from FCT - Foundation for Science and Technology through project UID/Multi/04326/2019.info:eu-repo/semantics/publishedVersio

Subclinical toxicity of calcineurin inhibitors in repeated protocol biopsies: an independent risk factor for chronic kidney allograft damage

The purpose of the prospective study was to determine the prevalence of subclinical toxicity of calcineurin inhibitors (CI) in repeated protocol renal allograft biopsies and to assess its impact on the development of chronic graft changes. A total of 424 biopsies were conducted in a cohort of 158 patients; of these biopsies, 158 were in the third week, 142 were in the third month and 124 were in the first year after transplantation. Histological signs of toxicity occurred in the third week in 33 (20.1%) patients, with persistence after CI dose reduction in the third month in 27 (19.0%) and in the first year in 23 (18.5%) patients. Of the toxic changes, 52% were clinically silent. At the end of the one-year follow-up, both subclinical and clinically manifest toxicity resulted in a similar progression of chronic changes quantified by Banff chronicity score and they significantly differed from the control group (P< 0.05). Subclinical toxicity affects a significant percentage of grafts; it occurs independently of dosage, blood level and type of applied CI. It is associated with the progression of chronic changes as early as in the first year after transplantation and represents an independent risk factor for chronic allograft damage. We report here our clinical approach to toxicity

Turning Milestones into Quantified Objectives: Food waste

This document sets out to define food waste, investigate how best it can be measured and provides a first assessment of the impacts of setting a food waste reduction target in the EU

Urotensin receptor in GtoPdb v.2023.1

The urotensin-II (U-II) receptor (UT, nomenclature as agreed by the NC-IUPHAR Subcommittee on the Urotensin receptor [26, 36, 94]) is activated by the endogenous dodecapeptide urotensin-II, originally isolated from the urophysis, the endocrine organ of the caudal neurosecretory system of teleost fish [7, 93]. Several structural forms of U-II exist in fish and amphibians [94]. The goby orthologue was used to identify U-II as the cognate ligand for the predicted receptor encoded by the rat gene gpr14 [2, 20, 63, 69, 72]. Human urotensin-II, an 11-amino-acid peptide [20], retains the cyclohexapeptide sequence of goby U-II that is thought to be important in ligand binding [61, 53, 10]. This sequence is also conserved in the deduced amino-acid sequence of rat urotensin-II (14 amino-acids) and mouse urotensin-II (14 amino-acids), although the N-terminal is more divergent from the human sequence [19]. A second endogenous ligand for the UT has been discovered in rat [86]. This is the urotensin II-related peptide, an octapeptide that is derived from a different gene, but shares the C-terminal sequence (CFWKYCV) common to U-II from other species. Identical sequences to rat urotensin II-related peptide are predicted for the mature mouse and human peptides [32]. UT exhibits relatively high sequence identity with somatostatin, opioid and galanin receptors [94]. The urotensinergic system displays an unprecedented repertoire of four or five ancient UT in some vertebrate lineages and five U-II family peptides in teleost fish [91]

Urotensin receptor in GtoPdb v.2021.3

The urotensin-II (U-II) receptor (UT, nomenclature as agreed by the NC-IUPHAR Subcommittee on the Urotensin receptor [26, 36, 93]) is activated by the endogenous dodecapeptide urotensin-II, originally isolated from the urophysis, the endocrine organ of the caudal neurosecretory system of teleost fish [7, 92]. Several structural forms of U-II exist in fish and amphibians [93]. The goby orthologue was used to identify U-II as the cognate ligand for the predicted receptor encoded by the rat gene gpr14 [2, 20, 63, 69, 72]. Human urotensin-II, an 11-amino-acid peptide [20], retains the cyclohexapeptide sequence of goby U-II that is thought to be important in ligand binding [61, 53, 10]. This sequence is also conserved in the deduced amino-acid sequence of rat urotensin-II (14 amino-acids) and mouse urotensin-II (14 amino-acids), although the N-terminal is more divergent from the human sequence [19]. A second endogenous ligand for the UT has been discovered in rat [86]. This is the urotensin II-related peptide, an octapeptide that is derived from a different gene, but shares the C-terminal sequence (CFWKYCV) common to U-II from other species. Identical sequences to rat urotensin II-related peptide are predicted for the mature mouse and human peptides [32]. UT exhibits relatively high sequence identity with somatostatin, opioid and galanin receptors [93]

Urotensin receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

The urotensin-II (U-II) receptor (UT, nomenclature as agreed by the NC-IUPHAR Subcommittee on the Urotensin receptor [26, 36, 89]) is activated by the endogenous dodecapeptide urotensin-II, originally isolated from the urophysis, the endocrine organ of the caudal neurosecretory system of teleost fish [7, 88]. Several structural forms of U-II exist in fish and amphibians. The goby orthologue was used to identify U-II as the cognate ligand for the predicted receptor encoded by the rat gene gpr14 [20, 62, 68, 70]. Human urotensin-II, an 11-amino-acid peptide [20], retains the cyclohexapeptide sequence of goby U-II that is thought to be important in ligand binding [53, 11]. This sequence is also conserved in the deduced amino-acid sequence of rat urotensin-II (14 amino-acids) and mouse urotensin-II (14 amino-acids), although the N-terminal is more divergent from the human sequence [19]. A second endogenous ligand for the UT has been discovered in rat [83]. This is the urotensin II-related peptide, an octapeptide that is derived from a different gene, but shares the C-terminal sequence (CFWKYCV) common to U-II from other species. Identical sequences to rat urotensin II-related peptide are predicted for the mature mouse and human peptides [32]. UT exhibits relatively high sequence identity with somatostatin, opioid and galanin receptors [89]