Search

Introduction During post-natal development, the organism is subjected to 2 metabolic transitions. The weaning transition is particularly interesting as it is associated with a change in glucose metabolism. O-GlcNAcylation is an ubiquitous post-translational modification, described as a nutrient sensor. The GlcNAc moiety is added and removed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. Interestingly, cardiac O-GlcNAc levels decrease throughout post-natal development but its regulatory mechanism and impact on proteins have never been studied under this condition. Objective Study the regulatory mechanism involved in O-GlcNAc regulation and its potential impact on proteins implied in cardiac metabolism. Method Hearts from 28 day-olds (D28) Wistar rats fed with a standard or low-carbohydrate (low-CHO) diet (D28F: 50% fat, 30% protein, 3% carbohydrates) during the weaning period (D12 to D28) were studied. O-GlcNAc levels and regulatory enzymes expression were evaluated by western blot. The OGA activity was evaluated with a spectrophotometric assay. The impact of selected protein expression in response to O-GlcNAc levels variations (Thiamet-G, OGA inhibitor) was evaluated on cell culture (HEK and COS). Results No change was reported on O-GlcNAc levels between the diets (D28: 1.00 ± 0.06; D28F: 0.99 ± 0.08). Cardiac OGA expression was 5 times lower in D28F however OGA activity remained stable (D28: 1.00 ± 0.03; D28F: 0.83 ± 0.16 AU). Protein expression, acetyl-CoA transferase 1 (ACAT1) and acetyl-CoA synthetase 1 (ACSS1), was reduced both in HEK and COS cells in responses to O-GlcNAc stimulation with Thiamet-G. Conclusion While OGA expression is lower with the low-CHO diet, OGA activity and O-GlcNAc levels remain stable. This indicates a strong regulatory mechanism to control O-GlcNAc levels throughout post-natal development. This regulatory mechanism could help to modulate the expression of key metabolic enzymes such as ACAT1 or ACSS1.

Introduction The young population, particularly at risk of septic shock, is rarely studied. The O-GlcNAcylation is a post-translational modification involved in cell survival, metabolism and stress response. We have shown that O-GlcNAc stimulation at the early phase of septic shock is beneficial in adult rats. Considering that O-GlcNAc levels are higher in the young, the impact of O-GlcNAc stimulation on sepsis in the young should be tested. Objective Evaluate if O-GlcNAc stimulation could improve sepsis outcomes in young. Method Endotoxemic shock was induced in 28 days old rats by injection of LPS (O111 :B4, 20 mg.kg−1–LPS) and compared to control rats (injection of saline–CTRL). One hour after LPS injection rats were randomly assigned to no therapy (LPS), fluidotherapy (saline, 10 mL.kg−1–LPS + R) ± NButGT (10 mg.kg−1–NButGT) to increase O-GlcNAc levels (n = 11 per group). Physiological functions and plasmatic markers were evaluated 2 hours later. Impact of treatment was evaluated with an adapted Pediatric RISk of Mortality score (PRISM score) and mortality was evaluated over 36 hours (n = 16 per group). Untargeted mass spectrometry was performed to identify cardiac O-GlcNAcylated proteins. Results LPS induced a shock (mean arterial pressure (MAP): CTRL: 67.2 ± 1.9; LPS: 50.7 ± 2.1 mmHg; P Conclusion O-GlcNAc stimulation acutely improves outcome in young septic shock rat. The impact of O-GlcNAcylation on ACLY is a potential issue to decipher the role of this protein during sepsis.

LPPL models have been widely used to describe the behaviour of stock prices during an endogenous bubble and to predict the most probable time of the regime switching. Although their utility has been proved in many papers, there is still a lack of consensus on the statistical robustness, as the estimators are obtained through a nonlinear optimization algorithm and they are sensitive to the initial values. In this paper we propose an extension of the approach from Liberatore (2011), using a time series peak detection algorithm.