Cardiovascular, endocrine and behavioural responses to suckling and permanent separation in goats

<p>Abstract</p> <p>Background</p> <p>Suckling can be a peaceful or vulnerable event for goats and kids, whereas, separation is suggested as stressful. The aim of this study was to investigate physiology and behaviour in these two different situations in dairy goats.</p> <p>Methods</p> <p>Four studies were performed with seven goats kept with their first-born kid in individual boxes. The goats were videotaped and heart rate and arterial blood pressure were recorded every minute by telemetry from parturition until 24 hours after separation. One to two days after parturition, Study 1 was performed with analyses of heart rate and blood pressure around a suckling. In Study 2, performed 3-5 days after parturition, blood sampling was done before, during and after suckling. Study 3 was performed 4-6 days post partum, with blood sampling before and after a permanent goat and kid separation. In addition, vocalisations were recorded after separation. Blood samples were obtained from a jugular vein catheter and analysed for plasma cortisol, β-endorphin, oxytocin, and vasopressin concentrations. Study 4 was performed during the first (N1) and second nights (N2) after parturition and the nights after Study 2 (N3) and 3 (N4). Heart rate, blood pressure and time spent lying down were recorded.</p> <p>Results</p> <p>The kids suckled 2 ± 0.2 times per hour and each suckling bout lasted 43 ± 15 s. In Study 1, heart rate and blood pressure did not change significantly during undisturbed suckling. In Study 2, plasma cortisol (P ≤ 0.05 during suckling and P ≤ 0.01 five minutes after suckling) and β-endorphin (P ≤ 0.05) concentrations increased during suckling, but oxytocin and vasopressin concentrations did not change. In Study 3, the goats and kids vocalised intensively during the first 20 minutes after separation, but the physiological variables were not affected. In Study 4, heart rate and arterial blood pressure declined gradually after parturition and were lowest during N4 (P ≤ 0.05) when the goats spent longer time lying down than during earlier nights (P ≤ 0.01 during N1 and N3 and P ≤ 0.05 during N2).</p> <p>Conclusions</p> <p>Suckling elevated plasma cortisol and β-endorphin concentrations in the goats. The intensive vocalisation in the goats after separation, earlier suggested to indicate stress, was not accompanied by cardiovascular or endocrine responses.</p

Circulating β-endorphin, adrenocorticotrophic hormone and cortisol levels of stallions before and after short road transport: stress effect of different distances

<p>Abstract</p> <p>Background</p> <p>Since transport evokes physiological adjustments that include endocrine responses, the objective of this study was to examine the responses of circulating β-endorphin, adrenocorticotrophic hormone (ACTH) and cortisol levels to transport stress in stallions.</p> <p>Methods</p> <p>Forty-two healthy Thoroughbred and crossbred stallions were studied before and after road transport over distances of 100, 200 and 300 km. Blood samples were collected from the jugular vein: first in a single box immediately before loading (pre-samples), then immediately after transport and unloading on arrival at the breeding stations (post-samples).</p> <p>Results</p> <p>An increase in circulating β-endorphin levels after transport of 100 km (<it>P </it>< 0.01), compared to basal values was observed. Circulating ACTH levels showed significant increases after transport of 100 km (<it>P </it>< 0.001) and 200 km (<it>P </it>< 0.001). Circulating cortisol levels showed significant increases after road transport over distances of 100, 200 and 300 km (<it>P </it>< 0.001). An effect of transport on β-endorphin, ACTH and cortisol variations was therefore evident for the different distances studied. No significant differences (<it>P </it>> 0.05) between horses of different ages and different breeds were observed for β-endorphin, ACTH and cortisol levels.</p> <p>Conclusion</p> <p>The results obtained for short term transportation of stallions showed a very strong reaction of the adrenocortical system. The lack of response of β-endorphin after transport of 200–300 km and of ACTH after transport of 300 km seems to suggest a soothing effect of negative feedback of ACTH and cortisol levels.</p

miR-27b inhibits fibroblast activation via targeting TGFB signaling pathway

Background: MicroRNAs are a group of small RNAs that regulate gene expression at the posttranscriptional level. They regulate almost every aspect of cellular processes. In this study, we investigated whether miR-27b regulates pulmonary fibroblast activation.Results: We found that miR-27b was down-regulated in fibrotic lungs and fibroblasts from an experimental mouse model of pulmonary fibrosis. The overexpression of miR-27b with a lentiviral vector inhibited TGFB1-stimulated mRNA expression of collagens (COL1A1, COL3A1, and COL4A1) and alpha-smooth muscle actin, and protein expression of Col3A1 and alpha-smooth muscle actin in LL29 human pulmonary fibroblasts. miR-27b also reduced contractile activity of LL29. TGFB receptor 1 and SMAD2 were identified as the targets of miR-27b by 3'-untranslated region luciferase reporter and western blotting assays.Conclusions: Our results suggest that miR-27b is an anti-fibrotic microRNA that inhibits fibroblast activation by targeting TGFB receptor 1 and SMAD2. This discovery may provide new targets for therapeutic interventions of idiopathic pulmonary fibrosis.Peer reviewedPhysiological SciencesOklahoma Center for Respiratory and Infectious Disease

Myc Stimulates Cell Cycle Progression Through the Activation of Cdk1 and Phosphorylation of p27

Cell cycle stimulation is a major transforming mechanism of Myc oncoprotein. This is achieved through at least three concomitant mechanisms: upregulation of cyclins and Cdks, downregulation of the Cdk inhibitors p15 and p21 and the degradation of p27. The Myc-p27 antagonism has been shown to be relevant in human cancer. To be degraded, p27 must be phosphorylated at Thr-187 to be recognized by Skp2, a component of the ubiquitination complex. We previously described that Myc induces Skp2 expression. Here we show that not only Cdk2 but Cdk1 phosphorylates p27 at the Thr-187. Moreover, Myc induced p27 degradation in murine fibroblasts through Cdk1 activation, which was achieved by Myc-dependent cyclin A and B induction. In the absence of Cdk2, p27 phosphorylation at Thr-187 was mainly carried out by cyclin A2-Cdk1 and cyclin B1-Cdk1. We also show that Cdk1 inhibition was enough for the synthetic lethal interaction with Myc. This result is relevant because Cdk1 is the only Cdk strictly required for cell cycle and the reported synthetic lethal interaction between Cdk1 and Myc.The work was supported by grant SAF2017-88026-R from MINECO, Spanish Government, to JL and MDD (partially funded by FEDER program from European Union). L.G.G. was recipient of FPI fellowship from Spanish Government. We are grateful Sandra Zunzunegui for technical assistance and John Sedivy and M. Dolores Delgado for helpful discussion