Conserved role of the urotensin II receptor 4 signalling pathway to control body straightness in a tetrapod.

Urp1 and Urp2 are two neuropeptides of the urotensin II family identified in teleost fish and mainly expressed in cerebrospinal fluid (CSF)-contacting neurons. It has been recently proposed that Urp1 and Urp2 are required for correct axis formation and maintenance. Their action is thought to be mediated by the receptor Uts2r3, which is specifically expressed in dorsal somites. In support of this view, it has been demonstrated that the loss of uts2r3 results in severe scoliosis in adult zebrafish. In the present study, we report for the first time the occurrence of urp2, but not of urp1, in two tetrapod species of the Xenopus genus. In X. laevis, we show that urp2 mRNA-containing cells are CSF-contacting neurons. Furthermore, we identified utr4, the X. laevis counterparts of zebrafish uts2r3, and we demonstrate that, as in zebrafish, it is expressed in the dorsal somatic musculature. Finally, we reveal that, in X. laevis, the disruption of utr4 results in an abnormal curvature of the antero-posterior axis of the tadpoles. Taken together, our results suggest that the role of the Utr4 signalling pathway in the control of body straightness is an ancestral feature of bony vertebrates and not just a peculiarity of ray-finned fishes.

O-positive blood type is associated with prolonged recurrence-free survival following curative resection of pancreatic neuroendocrine tumors.

BACKGROUND: The ABO blood group may influence the development and progression of cancer. In particular, the prognosis of patients with blood type O is better for pancreatic adenocarcinoma, although this has not been extensively explored in pancreatic neuroendocrine tumors (PanNET). OBJECTIVE: To assess the influence of the ABO and Rhesus blood types on the risk of recurrence in patients who underwent curative intent PanNET surgical resection. METHODS: All consecutive patients operated on for well-differentiated panNET in an expert center from 2003 to 2018 were retrospectively included. Blood group, Rhesus system, demographic and clinical data were collected. The primary endpoint was recurrence free survival (RFS). Factors associated with RFS were explored using Cox proportional hazard models. RESULTS: Overall, 300 patients (male 43%) were included, median age 54 years old (IQR 45-64). The ABO blood group distribution was similar to that of the French population. There was no association between blood group and tumor features. The median postoperative follow-up was 43.9 months (17.0-77.8). The 5- and 10-year RFS rates were 85 ± 4% and 71 ± 13% in O RhD + patients, versus 72 ± 4% and 63 ± 6% otherwise, respectively (p = 0.035). The O RhD + blood group was associated with a decreased risk of recurrence (HR 0.34, 95% CI [0.15-0.75]), p = 0.007 in multivariable analysis adjusted for age, ki67, functioning syndrome, resection margins, tumor size, lymph node status, oncogenetic syndrome. CONCLUSIONS: After curative-intent surgical resection for PanNET, patients with a non-O RhD + blood group may have an increased risk of recurrence and could benefit from closer follow-up.

Characterization of Gonadotropin-Releasing Hormone (GnRH) Genes From Cartilaginous Fish: Evolutionary Perspectives.

The neuropeptide gonadotropin-releasing hormone (GnRH) plays an important role in the control of reproductive functions. Vertebrates possess multiple GnRH forms that are classified into three main groups, namely GnRH1, GnRH2, and GnRH3. In order to gain more insights into the GnRH gene family in vertebrates, we sought to identify which paralogs of this family are present in cartilaginous fish. For this purpose, we searched the genomes and/or transcriptomes of three representative species of this group, the small-spotted catshark, Scyliorhinus canicula, the whale shark, Rhincodon typus and the elephant shark Callorhinchus milii. In each species, we report the identification of three GnRH genes. In catshark and whale shark, phylogenetic and synteny analysis showed that these three genes correspond to GnRH1, GnRH2, and GnRH3. In both species, GnRH1 was found to encode a novel form of GnRH whose primary structure was determined as follows: QHWSFDLRPG. In elephant shark, the three genes correspond to GnRH1a and GnRH1b, two copies of the GnRH1 gene, plus GnRH2. 3D structure prediction of the chondrichthyan GnRH-associated peptides (GAPs) revealed that catshark GAP1, GAP2, and elephant shark GAP2 peptides exhibit a helix-loop-helix (HLH) structure. This structure observed for many osteichthyan GAP1 and GAP2, may convey GAP biological activity. This HLH structure could not be observed for elephant shark GAP1a and GAP1b. As for all other GAP3 described so far, no typical 3D HLH structure was observed for catshark nor whale shark GAP3. RT-PCR analysis revealed that GnRH1, GnRH2, and GnRH3 genes are differentially expressed in the catshark brain. GnRH1 mRNA appeared predominant in the diencephalon while GnRH2 and GnRH3 mRNAs seemed to be most abundant in the mesencephalon and telencephalon, respectively. Taken together, our results show that the GnRH gene repertoire of the vertebrate ancestor was entirely conserved in the chondrichthyan lineage but that the GnRH3 gene was probably lost in holocephali. They also suggest that the three GnRH neuronal systems previously described in the brain of bony vertebrates are also present in cartilaginous fish.