Hyperactive HRAS dysregulates energetic metabolism in fibroblasts from patients with Costello syndrome via enhanced production of reactive oxidizing species

Germline-activating mutations in HRAS cause Costello syndrome (CS), a cancer prone multisystem disorder characterized by reduced postnatal growth. In CS, poor weight gain and growth are not caused by low caloric intake. Here, we show that constitutive plasma membrane translocation and activation of the GLUT4 glucose transporter, via reactive oxygen species-dependent AMP-activated protein kinase α and p38 hyperactivation, occurs in primary fibroblasts of CS patients, resulting in accelerated glycolysis and increased fatty acid synthesis and storage as lipid droplets. An accelerated autophagic flux was also identified as contributing to the increased energetic expenditure in CS. Concomitant inhibition of p38 and PI3K signaling by wortmannin was able to rescue both the dysregulated glucose intake and accelerated autophagic flux. Our findings provide a mechanistic link between upregulated HRAS function, defective growth and increased resting energetic expenditure in CS, and document that targeting p38 and PI3K signaling is able to revert this metabolic dysfunction.n

Vibration Qualification Campaign on Main Landing Gear System for High-Speed Compound Helicopter

Vibrations in helicopters have strong implications for their performance and safety, leading to the increased fatigue of components and reduced operational efficiency. As helicopters are designed to land on several types of surfaces, the landing gear system dissipates the impact on the ground and maintains stability during landing and take-off. These vibrations can arise from a variety of sources, such as aerodynamic loads, mechanical imbalances, and engine instabilities. In the present work, the authors describe the vibration qualification process of the main landing gear tailored to fast helicopters within the Clean Sky 2 Racer program. The method entails devising preliminary load sets that deform the structure in its key excited mode shapes to assess stresses and address the experimental campaign. A full-scale prototype model is then tested for sine sweep and random vibrations as per the Airbus Helicopter requirements in order to reach the final qualification and acceptance stage. Although the discussion centers on a landing gear structure, the described process could be extended to other critical equipment as well

Rassegna storica salernitana. N.s. A.32, n.1(2015)

La Società Salernitana di Storia Patria aderisce al progetto EleA e autorizza la pubblicazione del fascicoloN.s. A.32, n.1(2015): Riassunti/abstracts, P. 7 ; Vitolo, G., Riccardo Senescalco e gli inizi della penetrazione cavense in Terra d'Otranto. Contributo alla diplomatica signorile, P. 11 ; Kiesewetter, A., L'acquisto e l'occupazione del litorale meridionale dell'Albania da parte di re Carlo I d'Angiò (1279-1283), P. 27 ; D'Atri, S., Medici salernitani a Ragusa (Dubrovnik) nel XIV secolo, P. 63 ; Mello, M., Paestum. Vescovi e territorio tra XVI e XVIII secolo. Nuovi documenti, P. 85 ; Belardo, G., Un affresco di papa Urbano V nella chiesa dei santi Pietro e Benedetto in Polla (SA), P. 109 ; Volpe, F., Gli Altomare nella storia feudale del Cilento, P. 127 ; D'Angelo, M., Alcune novità sul Bottigliero ritrattista, P. 169 ; Carlone, C., Note biografiche di Melchiorre Guerriero, P. 197 ; Rassegne, P. 211 ; Recensioni, P. 231-240Sul recto del frontespizio: fasc. 63 della Nuova serie (annata LXXIV dalla fondazione

Induction of mitogen-activated protein kinases is proportional to the amount of pressure overload.

Pressure overload has been shown to induce mitogen activated protein kinases (MAPKs) and reactivate the atrial natriuretic factor in the heart. To test the sensitivity of these signals to pressure overload, we assayed the activity of MAPKs extracellular signal-regulated kinase, c-Jun N-terminal kinase 1, and p38 in protein lysates from the left ventricle (LV) or white blood cells (WBC) isolated from aortic banded mice with varying levels of pressure overload. In separated mice we measured atrial natriuretic factor mRNA levels by Northern blotting. As expected, a significant induction of atrial natriuretic factor mRNA levels was observed after aortic banding, and it significantly correlated with the trans-stenotic systolic pressure gradient but not with the LV weight:body weight ratio. In contrast, a significant correlation with systolic pressure gradient or LV weight:body weight ratio was observed for all of the MAPK activity detected in LV samples or WBCs. Importantly, LV activation of MAPKs significantly correlated with their activation in WBCs from the same animal. To test whether MAPK activation in WBCs might reflect uncontrolled blood pressure levels in humans, we assayed extracellular signal-regulated kinase, c-Jun N-terminal kinase 1, and p38 activation in WBCs isolated from normotensive volunteers, hypertensive patients with controlled blood pressure values, or hypertensive patients with uncontrolled blood pressure values. Interestingly, in hypertensive patients with controlled blood pressure values, LV mass and extracellular signal-regulated kinase phosphorylation were significantly reduced compared with those in hypertensiv