Oxytocin-Gly-Lys-Arg: A Novel Cardiomyogenic Peptide

Background: Oxytocin (OT), synthesized in the heart, has the ability to heal injured hearts and to promote cardiomyogenesis from stem cells. Recently, we reported that the OT-GKR molecule, a processing intermediate of OT, potently increased the spontaneous formation of cardiomyocytes (CM) in embryonic stem D3 cells and augmented glucose uptake in newborn rat CM above the level stimulated by OT. In the present experiments, we investigated whether OT-GKR exists in fetal and newborn rodent hearts, interacts with the OT receptors (OTR) and primes the generation of contracting cells expressing CM markers in P19 cells, a model for the study of early heart differentiation. Methodology/Principal Findings: High performance liquid chromatography of newborn rat heart extracts indicated that OT-GKR was a dominant form of OT. Immunocytochemistry of mouse embryos (embryonic day 15) showed cardiac OT-GKR accumulation and OTR expression. Computerized molecular modeling revealed OT-GKR docking to active OTR sites and to V1a receptor of vasopressin. In embryonic P19 cells, OT-GKR induced contracting cell colonies and ventricular CM markers more potently than OT, an effect being suppressed by OT antagonists and OTR-specific small interfering (si) RNA. The V1a receptor antagonist and specific si-RNA also significantly reduced OT-GKR-stimulated P19 contracting cells. In comparison to OT, OT-GKR induced in P19 cells less a-actinin, myogenin and MyoD mRNA, skeletal muscle markers. Conclusions/Significance: These results raise the possibility that C-terminally extended OT molecules stimulate C

Neuroendocrine regulation of salt and water metabolism

Abstract Neurons which release atrial natriuretic peptide (ANPergic neurons) have their cell bodies in the paraventricular nucleus and in a region extending rostrally and ventrally to the anteroventral third ventricular (AV3V) region with axons which project to the median eminence and neural lobe of the pituitary gland. These neurons act to inhibit water and salt intake by blocking the action of angiotensin II. They also act, after their release into hypophyseal portal vessels, to inhibit stressinduced ACTH release, to augment prolactin release, and to inhibit the release of LHRH and growth hormone-releasing hormone. Stimulation of neurons in the AV3V region causes natriuresis and an increase in circulating ANP, whereas lesions in the AV3V region and caudally in the median eminence or neural lobe decrease resting ANP release and the response to blood volume expansion. The ANP neurons play a crucial role in blood volume expansion-induced release of ANP and natriuresis since this response can be blocked by intraventricular (3V) injection of antisera directed against the peptide. Blood volume expansion activates baroreceptor input via the carotid, aortic and renal baroreceptors, which provides stimulation of noradrenergic neurons in the locus coeruleus and possibly also serotonergic neurons in the raphe nuclei. These project to the hypothalamus to activate cholinergic neurons which then stimulate the ANPergic neurons. The ANP neurons stimulate the oxytocinergic neurons in the paraventricular and supraoptic nuclei to release oxytocin from the neural lobe which circulates to the atria to stimulate the release of ANP. ANP causes a rapid reduction in effective circulating blood volume by releasing cyclic GMP which dilates peripheral vessels and also acts within the heart to slow its rate and atrial force of contraction. The released ANP circulates to the kidney where it acts through cyclic GMP to produce natriuresis and a return to normal blood volume

Rab-dependent vesicular traffic affects female gametophyte development in Arabidopsis

Eukaryotic cells rely on the accuracy and efficiency of vesicular traffic. In plants, disturbances in vesicular trafficking are well studied in quickly dividing root meristem cells or polar growing root hairs and pollen tubes. The development of the female gametophyte, a unique haploid reproductive structure located in the ovule, has received far less attention in studies of vesicular transport. Key molecules providing the specificity of vesicle formation and its subsequent recognition and fusion with the acceptor membrane are Rab proteins. Rabs are anchored to membranes by covalently linked geranylgeranyl group(s) that are added by the Rab geranylgeranyl transferase (RGT) enzyme. Here we show that Arabidopsis plants carrying mutations in the gene encoding the beta subunit of RGT (rgtb1) exhibit severely disrupted female gametogenesis and this effect is of sporophytic origin. Mutations in rgtb1 lead to internalization of the PIN1 and PIN3 proteins from the basal membranes to vesicles in pro-vascular cells of the funiculus. Decreased transport of auxin out of the ovule is accompanied by auxin accumulation in a tissue surrounding the growing gametophyte. In addition, female gametophyte development arrests at the uni- or binuclear stage in a significant portion of the rgtb1 ovules. These observations suggest that communication between the sporophyte and the developing female gametophyte relies on Rab dependent vesicular traffic of the PIN1 and PIN3 transporters and auxin efflux out of the ovule.Joanna Rojek, Matthew R Tucker, Sara C Pinto, Michał Rychłowski, Małgorzata Lichocka, Hana Soukupova ... et al

Prevalence of hypoparathyroidism after thyroid surgery depending on diagnosis, the extent of the procedure, and the presence of parathyroid glands in the postoperative examination.

Introduction Postoperative hypoparathyroidism can be one of the complications associated with total thyroid removal due to cancer or benign goitre. Purpose The paper aimed to evaluate the prevalence of hypoparathyroidism in patients operated on due to thyroid cancer and nodular goitre, including procedures performed between January 2015 and March 2019 at the Department of Oncological Surgery of the Medical University of Silesia in Katowice. Material and methods The studied group consisted of 595 patients operated on due to cancer and benign nodular goitres. Calcium and phosphate metabolism was assessed using PTH and ionised calcium tests four hours after the surgery. Ionised calcium was checked 30 days after the procedure. Patients who had borderline or below-normal PTH levels in the postoperative period were also subjected to PTH testing after 30 days. In patients with low PTH levels, supplementation with calcium and vitamin D3 was introduced after the surgery. Results Compared to patients operated on for benign goitres, persons diagnosed with cancer were significantly more likely to have PTH levels below 15 pg/ml and serum ionised calcium levels below 4 mg/dl after 30 days following the surgery. The recovery rate was 65.05% vs 82.6% (p < 0.003) and 64.2% vs 84.25% (p < 0.001). The results were similar among patients who underwent lateral and central lymphadenectomy – 33.3% vs 67.3% (p < 0.021) and 25.6% vs 67.6% (p < 0.018). In patients with mild goitres, no significant differences in the recovery rate were observed – 82.6% vs 92.8% (p < 0.327) and 84.25% vs 92.3% (p < 0.437). Patients in whom parathyroid glands were found in the postoperative material were significantly more likely to have decreased PTH and calcium levels after 30 days following the procedure. The recovery rate was 64.1% vs 78.9% (p < 0.027) and 58.06% vs 80.8% (p < 0.004). Conclusions Hypoparathyroidism is not an uncommon occurrence after thyroidectomy, even in facilities with extensive experience in this matter. Compared to total thyroid removal due to benign goitre, surgery for cancer with associated central and lateral lymphadenectomy significantly increases the risk of postoperative hypoparathyroidism. In surgical practice, it is reasonable to conduct routine Ca and PTH level checks after the procedure and 30 days following thyroidectomy