The Influence of Recovery and Training Phases on Body Composition, Peripheral Vascular Function and Immune System of Professional Soccer Players

Professional soccer players have a lengthy playing season, throughout which high levels of physical stress are maintained. The following recuperation period, before starting the next pre-season training phase, is generally considered short but sufficient to allow a decrease in these stress levels and therefore a reduction in the propensity for injury or musculoskeletal tissue damage. We hypothesised that these physical extremes influence the body composition, blood flow, and endothelial/immune function, but that the recuperation may be insufficient to allow a reduction of tissue stress damage. Ten professional football players were examined at the end of the playing season, at the end of the season intermission, and after the next pre-season endurance training. Peripheral blood flow and body composition were assessed using venous occlusion plethysmography and DEXA scanning respectively. In addition, selected inflammatory and immune parameters were analysed from blood samples. Following the recuperation period a significant decrease of lean body mass from 74.4±4.2 kg to 72.2±3.9 kg was observed, but an increase of fat mass from 10.3±5.6 kg to 11.1±5.4 kg, almost completely reversed the changes seen in the pre-season training phase. Remarkably, both resting and post-ischemic blood flow (7.3±3.4 and 26.0±6.3 ml/100 ml/min) respectively, were strongly reduced during the playing and training stress phases, but both parameters increased to normal levels (9.0±2.7 and 33.9±7.6 ml/100 ml/min) during the season intermission. Recovery was also characterized by rising levels of serum creatinine, granulocytes count, total IL-8, serum nitrate, ferritin, and bilirubin. These data suggest a compensated hypo-perfusion of muscle during the playing season, followed by an intramuscular ischemia/reperfusion syndrome during the recovery phase that is associated with muscle protein turnover and inflammatory endothelial reaction, as demonstrated by iNOS and HO-1 activation, as well as IL-8 release. The data provided from this study suggest that the immune system is not able to function fully during periods of high physical stress. The implications of this study are that recuperation should be carefully monitored in athletes who undergo intensive training over extended periods, but that these parameters may also prove useful for determining an individual's risk of tissue stress and possibly their susceptibility to progressive tissue damage or injury

Progesterone Receptor Activates Msx2 Expression by Downregulating TNAP/Akp2 and Activating the Bmp Pathway in EpH4 Mouse Mammary Epithelial Cells

Previously we demonstrated that EpH4 mouse mammary epithelial cells induced the homeobox transcription factor Msx2 either when transfected with the progesterone receptor (PR) or when treated with Bmp2/4. Msx2 upregulation was unaffected by Wnt inhibitors s-FRP or Dkk1, but was inhibited by the Bmp antagonist Noggin. We therefore hypothesized that PR signaling to Msx2 acts through the Bmp receptor pathway. Herein, we confirm that transcripts for Alk2/ActR1A, a non-canonical BmpR Type I, are upregulated in mammary epithelial cells overexpressing PR (EpH4-PR). Increased phosphorylation of Smads 1,5, 8, known substrates for Alk2 and other BmpR Type I proteins, was observed as was their translocation to the nucleus in EpH4-PR cells. Analysis also showed that Tissue Non-Specific Alkaline Phosphatase (TNAP/Akp2) was also found to be downregulated in EpH4-PR cells. When an Akp2 promoter-reporter construct containing a ½PRE site was transfected into EpH4-PR cells, its expression was downregulated. Moreover, siRNA mediated knockdown of Akp2 increased both Alk2 and Msx2 expression. Collectively these data suggest that PR inhibition of Akp2 results in increased Alk2 activity, increased phosphorylation of Smads 1,5,8, and ultimately upregulation of Msx2. These studies imply that re-activation of the Akp2 gene could be helpful in downregulating aberrant Msx2 expression in PR+ breast cancers

Temporal-Difference Reinforcement Learning with Distributed Representations

Temporal-difference (TD) algorithms have been proposed as models of reinforcement learning (RL). We examine two issues of distributed representation in these TD algorithms: distributed representations of belief and distributed discounting factors. Distributed representation of belief allows the believed state of the world to distribute across sets of equivalent states. Distributed exponential discounting factors produce hyperbolic discounting in the behavior of the agent itself. We examine these issues in the context of a TD RL model in which state-belief is distributed over a set of exponentially-discounting “micro-Agents”, each of which has a separate discounting factor (γ). Each µAgent maintains an independent hypothesis about the state of the world, and a separate value-estimate of taking actions within that hypothesized state. The overall agent thus instantiates a flexible representation of an evolving world-state. As with other TD models, the value-error (δ) signal within the model matches dopamine signals recorded from animals in standard conditioning reward-paradigms. The distributed representation of belief provides an explanation for the decrease in dopamine at the conditioned stimulus seen in overtrained animals, for the differences between trace and delay conditioning, and for transient bursts of dopamine seen at movement initiation. Because each µAgent also includes its own exponential discounting factor, the overall agent shows hyperbolic discounting, consistent with behavioral experiments