Return to competitive gymnastics training in the UK following the first COVID-19 national lockdown.

Following the outbreak of COVID-19 (coronavirus), the UK entered a national lockdown, and all sport was suspended. The study aimed to explore the process of returning to gymnastics training after several months away from the gym, with a particular interest towards training load and injury. Twenty-six, national programmed gymnasts from Men's artistic, Women's artistic and Trampoline gymnastics recorded training load and injury whilst returning to training. At the end of data collection, three coaches were interviewed to further explore the experiences and practices of returning to training. Home-based training during lockdown was seen as beneficial in maintaining a level of fitness. Coaches described a gradual increase in training to reduce the risk of injury, and this partly explains a non-significant association between training load and a substantial injury (p = 0.441). However, week-to-week changes in training load following periods of additional restrictions (additional lockdown, periods of isolation, or substantial restrictions) were not always gradual. There was a significant association between an injury in the preceding week (niggle or substantial injury to a different body part) and a substantial injury in the subsequent week (RR: 5.29, p = 0.011). Monitoring training was described to be a useful practice during the process of returning to training. Coaches believed that although the short-term development of their gymnasts was affected, the long-term development would not be impacted from COVID-19. It is anticipated that learnings from this study can be applied to future practices and situations, particularly when gymnasts are away from the gym for an extended period.

The influence of growth and training loads on injury risk in competitive trampoline gymnasts.

There is currently limited research exploring the relationship between growth, training load and injury in gymnasts. Twenty-one national level, trampoline gymnasts recorded training load and injury for 8-weeks. Percentage of predicted adult height (%PAH) was calculated using the Khamis-Roche method and used to define growth spurt status. Training load was calculated using the session rate of perceived exertion and analysed as differential loads and as a 7-day exponentially weighted moving average (EWMA7day). There was a significant non-linear association between %PAH and the probability of injury when adjusting for either training load metric (differential load, P = 0.015; EWMA7day; P = 0.008), with the highest injury risk estimated at ~90% PAH (circa growth spurt). The probability of injury significantly increased with increases in EWMA7day training load (RR: 1.88 95% CI: 1.21- 2.91, P = 0.005) but not with differential load. No significant interaction between %PAH, training load and the probability of injury were observed. Data suggest that competitive trampoline gymnasts are at an increased risk of injury during the adolescent growth spurt or with higher weekly training loads. Coaches should be educated and encouraged to identify periods of rapid growth and monitor training load, to reduce the risk of injury.

Mutant ras-induced proliferation of human thyroid epithelial cells requires three effector pathways.

Ras mutations occur as an early event in many human tumours of epithelial origin, including thyroid. Using primary human thyroid epithelial cells to model tumour initiation by Ras, we have shown previously that activation of both the MAP kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) effector pathways are necessary, but even when activated together are not sufficient, for Ras-induced proliferation. Here, we show that a third effector, RalGEF, is also activated by Ras in these cells, that this activation is necessary for Ras-induced proliferation, and furthermore that in combination with the MAPK and PI3K effectors, it is able to reproduce the proliferative effect of activated Ras. The requirement for three effector pathways indicates a more robust control of cell proliferation in this normal human epithelial cell type than has been displayed in previous similar studies using rodent and human cell lines. Our findings highlight the importance of the appropriate cellular context in models of Ras-induced tumour development.

Regulation of phosphatidylinositol 3-kinase activity and phosphatidylinositol 3,4,5-trisphosphate accumulation by neutrophil priming agents.

Neutrophil priming by agents such as TNF-alpha and GM-CSF causes a dramatic increase in the response of these cells to secretagogue agonists and affects the capacity of neutrophils to induce tissue injury. In view of the central role of phosphatidylinositol 3-kinase (PI3-kinase) in regulating NADPH oxidase activity we examined the influence of priming agents on agonist-stimulated phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) accumulation in human neutrophils. Pretreatment of neutrophils with TNF-alpha or GM-CSF, while not influencing fMLP-stimulated PtdIns(3,4,5)P3 accumulation at 5 s, caused a major increase in PtdIns(3,4,5)P3 at later times (10-60 s), which paralleled the augmented superoxide anion (O2-) response. The intimate relationship between PtdIns(3,4,5)P3 accumulation and O2- release was confirmed using platelet-activating factor, which caused full but transient priming of both responses. Likewise, LY294002, a PI3-kinase inhibitor, and genistein, a tyrosine kinase inhibitor, caused parallel inhibition of O2- generation and PtdIns(3,4,5)P3 accumulation; in contrast, radicicol, which inhibits receptor-mediated activation of p85 PI3-kinase, had no effect on either response. Despite major increases in PI3-kinase activity observed in p85 and anti-phosphotyrosine immunoprecipitates in growth factor-stimulated smooth muscle cells, no such increase was observed in primed/stimulated neutrophils. In contrast, both fMLP and TNF-alpha alone caused a 3-fold increase in PI3-kinase activity in p110gamma PI3-kinase immunoprecipitates. p21(ras) activation (an upstream regulator of PI3-kinase) was unaffected by priming. These data demonstrate that timing and magnitude of PtdIns(3,4,5)P3 accumulation in neutrophils correlate closely with O2- generation, that PI3-kinase-gamma is responsible for the enhanced PtdIns(3,4,5)P3 production seen in primed cells, and that factors other than activation of p21(ras) underlie this response.

The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation.

Recent studies have shown that phox homology (PX) domains act as phosphoinositide-binding motifs. The majority of PX domains studied show binding to phosphatidylinositol 3-monophosphate (PtdIns(3)P), an association that allows the host protein to localize to membranes of the endocytic pathway. One issue, however, is whether PX domains may have alternative phosphoinositide binding specificities that could target their host protein to distinct subcellular compartments or allow their allosteric regulation by phosphoinositides other than PtdIns(3)P. It has been reported that the PX domain of sorting nexin 1 (SNX1) specifically binds phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) (Zhong, Q., Lazar, C. S., Tronchere, H., Sato, T., Meerloo, T., Yeo, M., Songyang, Z., Emr, S. D., and Gill, G. N. (2002) Proc. Natl. Acad. Sci. U. S. A. 99, 6767-6772). In the present study, we have shown that whereas SNX1 binds PtdIns(3,4,5)P(3) in protein:lipid overlay assays, in liposomes-based assays, binding is observed to PtdIns(3)P and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P(2)) but not to PtdIns(3,4,5)P(3). To address the significance of PtdIns(3,4,5)P(3) binding, we examined the subcellular localization of SNX1 under conditions in which plasma membrane PtdIns(3,4,5)P(3) levels were significantly elevated. Under these conditions, we failed to observe association of SNX1 with this membrane. However, consistent with the binding to PtdIns(3)P and PtdIns(3,5)P(2) being of more physiological significance was the observation that the association of SNX1 with an early endosomal compartment was dependent on a 3-phosphoinositide-binding PX domain and the presence of PtdIns(3)P on this compartment. Finally, we have shown that the PX domain-dependent/early endosomal association of SNX1 is important for its ability to regulate the targeting of internalized epidermal growth factor receptor for lysosomal degradation.