Muscle pain induced by hypertonic saline in the knee extensors decreases single-limb isometric time to task failure

Purpose: Increased nociceptive activity and the experience of exercise-induced pain (EIP) may contribute to fatigue during endurance exercise. To investigate this, a pain model that produces pain similar to EIP and decouples its’ relationship to exercise intensity is required. This study 1) compared the quality of pain caused by a hypertonic saline injection into the vastus lateralis in resting and exercise conditions, and 2) investigated whether this pain contributes to changes in time to task failure. Methods: On separate days, eighteen participants completed a time to task failure at 20% maximal voluntary torque (MVT), a resting hypertonic saline intramuscular injection, and in a further three visits a time to task failure at 10% MVT following injection of isotonic saline, hypertonic saline or a control (no injection). Results: In a subset of eligible participants (n = 12), the hypertonic saline combined with 10% MVT produced a qualitative experience of pain (assessed by the McGill Pain Questionnaire) that felt similar to EIP. 10% MVT with hypertonic saline significantly elevated pain intensity in the first 20% of the time to task failure and caused a significantly (P < 0.05) shorter time to task failure (448 ± 240 s) compared with the isotonic saline (605 ± 285 s) and control (514 ± 197 s) conditions. Conclusion: These findings demonstrate that hypertonic saline increases the intensity of pain during exercise, which results in a faster occurrence of exercise-induced fatigue. These results provide important evidence supporting pain as a limiting factor in endurance performance

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Loss of 4E-BP1 expression has been linked to cancer progression and resistance to mTOR inhibitors, but the mechanism underlying 4E-BP1 downregulation in tumors remains unclear. Here we identify Snail as a strong transcriptional repressor of 4E-BP1. We find that 4E-BP1 expression inversely correlates with Snail level in cancer cell lines and clinical specimens. Snail binds to three E-boxes present in the human 4E-BP1 promoter to repress transcription of 4E-BP1. Ectopic expression of Snail in cancer cell lines lacking Snail profoundly represses 4E-BP1 expression, promotes cap-dependent translation in polysomes, and reduces the anti-proliferative effect of mTOR kinase inhibitors. Conversely, genetic and pharmacological inhibition of Snail function restores 4E-BP1 expression and sensitizes cancer cells to mTOR kinase inhibitors by enhancing 4E-BP1-mediated translation-repressive effect on cell proliferation and tumor growth. Our study reveals a critical Snail-4E-BP1 signaling axis in tumorigenesis, and provides a rationale for targeting Snail to improve mTOR-targeted therapies

Argonne National Laboratory Reports

Portions of the cesium-uranium-oxygen system have been investigated between 873 and 1273°K and a phase diagram has been constructed using our data and the data of other workers in the field. Thermodynamic and kinetic data have been used to examine the reactions that occur in fast-reactor fuel pins between fission-product cesium and the uranium oxide blanket. It was concluded that at the low oxygen potentials existing at the interface between the uranium-plutonium mixed-oxide and the uranium oxide blanket, Cs₂UO₄ is the only Cs-U-O compound expected to be formed in the uranium oxide blanket