High-intensity muscle contraction (HiMC) is known to induce muscle protein synthesis, a process in which mechanistic target of rapamycin (mTOR) was reported to play a critical role. However, the mechanistic details have not been completely elucidated. Here, we investigated whether Akt plays a role in regulating HiMC-induced mTORC1 activation and muscle protein synthesis using a rodent model of resistance exercise and MK2206 (an Akt kinase inhibitor). The right gastrocnemius muscle of male C57BL/6J mice aged 10 weeks was isometrically contracted via percutaneous electrical stimulation (100 Hz, 5 sets of ten 3 s contractions, 7 s rest between contractions, 3 min rest between sets), while the left gastrocnemius muscle served as a control. Vehicle or MK2206 was injected intraperitoneally 6 h before contraction. MK2206 inhibited both resting and HiMC-induced phosphorylation of Akt1 and Akt2. MK2206 also inhibited the resting phosphorylation of p70S6K and 4E-BP1, which are downstream targets of mTORC1; however, it did not inhibit the HiMC-induced increase in phosphorylation of these targets. Similarly, MK2206 inhibited the resting, but not the resistance exercise-induced muscle protein synthesis.  https://www.selleckchem.com/products/dmog.html  Based on these observations, we conclude that although Akt2 regulates resting mTORC1 activity and muscle protein synthesis, HiMC-induced increases in mTORC1 activity and muscle protein synthesis are Akt-independent processes.After the airways have been formed by branching morphogenesis the gas-exchange area of the developing lung is enlarged by the formation of new alveolar septa (alveolarization). The septa themselves mature by a reduction of their double layered capillary networks to single layered ones (microvascular maturation). Alveolarization in mice is subdivided into a first phase (postnatal days 4-21, classical alveolarization), where new septa are lifted off from immature pre-existing septa, and a second phase (days 14-adulthood, continued alveolarization), where new septa are formed from mature septa. Tenascin-C (TNC) is a multi-domain extracellular matrix protein contributing to organogenesis and tumorigenesis. It is highly expressed during classical alveolarization, but afterwards it is markedly reduced. To study the effect of TNC deficiency on postnatal lung development, the formation and maturation of the alveolar septa was followed stereologically. Furthermore, the number of proliferating (Ki-67-positive) and TUNEL-positive cells was estimated. In TNC deficient mice for both phases of alveolarization a delay and catch-up was observed. Cell proliferation was increased at days 4 and 6, at day 7 thick septa with an accumulation of capillaries and cells were observed, and the number of TUNEL-positive cells (dying cells or DNA-repair) was increased at day 10. While at days 15 and 21 premature microvascular maturation was detected, the microvasculature was less mature at day 60 as compared to wildtype. No differences were observed in adulthood. We conclude that TNC contributes to the formation of new septa, to microvascular maturation, and to cell proliferation and migration during postnatal lung development.RATIONALE In newborns, it is unclear how NHF generates positive airway pressure. In addition, the reported benefits of NHF such as reduction in work of breathing may be independent of airway pressure. The authors hypothesized that during NHF the area of leak and the flow determines airway pressure and that NHF can reduce the required minute ventilation to maintain gas exchange. METHODS In response to NHF, pressure was measured in the upper airways of 9 newborns and ventilation was measured in another group of 17 newborns. In a bench model, airway pressures were measured during NHF with different prong size, nare size and flow. RESULTS The airway pressures during NHF 8 L/min was greater when a larger cannula versus smaller cannula was used (P less then 0.05). NHF reduced minute ventilation in 16 out of 17 neonates with a mean decrease of 24% from a baseline of 0.66 L/min (SD 0.21), P less then 0.001, and was unrelated to changes in airway pressure; SpO2 and tissue CO2 were unchanged. In the bench model, the airway pressure remained less then 2 cmH2O when less then 50% of the "nare" was occluded by the prongs. As the leak area decreased, due to smaller nare or larger cannula, the airway pressure increased exponentially and was dependent on flow. CONCLUSIONS In newborns, NHF using room air substantially reduced minute ventilation without affecting gas exchange irrespective of a decrease or an increase of respiratory rate. NHF generates low positive airway pressure that exponentially increases with flow and occlusion of the nares.Female sex hormones fluctuate in a predictable manner throughout the menstrual cycle in eumenorrheic women. In studies conducted in both animal and humans, estrogen and progesterone have been found to exert individual metabolic effects during both rest and exercise, suggesting that estrogen may cause an increase in fat oxidation during exercise. However, not all studies find these metabolic changes with the natural physiological variation in the sex hormones. To date, no studies have investigated whether whole body peak fat oxidation rate (PFO) and maximal fat oxidation intensity (FATmax) are affected at different time points [mid-follicular (MF), late-follicular (LF), and mid-luteal (ML)] in the menstrual cycle, where plasma estrogen and progesterone are either at their minimum or maximum. We hypothesized that an increased plasma estrogen concentration together with low progesterone concentration in LF would result in a modest but significant increase in PFO. We found no differences in body weight, body composition, or peak oxygen uptake (V̇o2peak) between any of the menstrual phases in the 19 healthy, young eumenorrheic women included in this study. PFO [MF 0.379 (0.324-0.433) g/min; LF 0.375 (0.329-0.421) g/min; ML 0.382 (0.337-0.442) g/min; mean ± (95% CI)] and resting plasma free fatty acid concentrations [MF 392 (293-492) µmol/l; LF 477 (324-631) µmol/l; ML 396 (285-508) µmol/L] were also similar across the menstrual cycle phases. Contrary to our hypothesis, we conclude that the naturally occurring fluctuations in the sex hormones estrogen and progesterone do not affect the whole body PFO and FATmax in young eumenorrheic women measured during a graded exercise test.NEW & NOTEWORTHY Menstrual cycle phase does not affect the peak fat oxidation rate during a graded exercise test. Natural physiological fluctuations in estrogen do not increase peak fat oxidation rate. FATmax is not influenced by menstrual cycle phase in healthy, young eumenorrheic women.