Epigenetic control of exercise adaptations in the equine athlete: Current evidence and future directions.

Horses (Equus ferus caballus) have evolved over the past 300 years in response to man-made selection for particular athletic traits. Some of the selected traits were selected based on the size and horses' muscular power (eg Clydesdales), whereas other breeds were bred for peak running performance (eg Thoroughbred and Arabian). Although the physiological changes and some of the cellular adaptations responsible for athletic potential of horses have been identified, the molecular mechanisms are only just beginning to be comprehensively investigated. The purpose of this review was to outline and discuss the current understanding of the molecular mechanisms underpinning the athletic performance and cardiorespiratory fitness in athletic breeds of horses. A brief review of the biology of epigenetics is provided, including discussion on DNA methylation, histone modifications and small RNAs, followed by a summary and critical review of the current work on the exercise-induced epigenetic and transcriptional changes in horses. Important unanswered questions and currently unexplored areas that deserve attention are highlighted. Finally, a rationale for the analysis of epigenetic modifications in the context with exercise-related traits and ailments associated with athletic breeds of horses is outlined in order to help guide future research.

Oxygen recovery kinetics in the forearm flexors of multiple ability groups of rock climbers.

The purpose of this study was to determine muscle tissue oxidative capacity and recovery in intermediate, advanced, and elite rock climbers. Forty-four male participants performed (a) sustained and (b) intermittent contractions at 40% of maximal volitional contraction (MVC) on a sport-specific fingerboard until volitional fatigue. Near-infrared spectroscopy was used to assess muscle tissue oxygenation during both the exercise and the 5-minutes passive recovery period, in the flexor digitorum profundus (FDP) and flexor carpi radialis (FCR). During the sustained contraction only, muscle tissue deoxygenation (O2 debt) in the FDP and FCR was significantly greater in elite climbers compared with the control, intermediate, and advanced groups (FDP: 32 vs. 15, 19, 22%; FCR: 19 vs. 11, 8, 15%, respectively). However, elite climbers had a significantly quicker time to half recovery (T1/2) than the control and intermediate groups in the FDP (8 vs. 95 and 47 seconds, respectively) and the FCR (7 vs. 30 and 97 seconds, respectively) because the O2% recovered per second being significantly greater (FDP: 4.2 vs. 0.7 and 0.3; FCR: 4.8 vs. 0.1 and 0.2, respectively). Furthermore, during the intermittent contraction, T1/2 in elite climbers was significantly quicker compared with the control and intermediate groups in the FDP (8 vs. 93 and 83 seconds, respectively) and FCR (16 vs. 76 and 50 seconds, respectively). Consequently, lower-level climbers should focus training on specific intermittent fatigue protocols. Competition or elite climbers should make use of appropriate rests on route to aid recovery and increase the chances of reaching the next hold.

New mouse models for recessive retinitis pigmentosa caused by mutations in the Pde6a gene.

The heterotetrameric phosphodiesterase (PDE) 6 complex, made up of alpha, beta and two gamma subunits, regulates intracellular cGMP levels by hydrolyzing cGMP in response to light activation of G protein coupled receptors in cones and rods, making it an essential component of the visual phototransduction cascade [Zhang, X. and Cote, R.H. (2005) cGMP signaling in vertebrate retinal photoreceptor cells. Front. Biosci., 10, 1191-1204.]. Using a genetic positional candidate cloning strategy, we have identified missense mutations within the catalytic domain of the Pde6a gene in two mouse models from an ethyl nitrosourea chemical mutagenesis screen. In these first small rodent models of PDE6A, significantly different biochemical outcomes and rates of degeneration of murine photoreceptor cells were observed, indicating allelic variation and previously unrecognized structure-function relationships. In addition, these new models reveal that the mutations not only affect the function of the PDE6A protein itself, but also the level of PDE6B within the retina. Finally, we show that the variation of the disease phenotype by background modifier genes may be dependent upon the particular disease allele present.

Identification, characterization and functional expression of a tyrosine ammonia-lyase and its mutants from the photosynthetic bacterium Rhodobacter sphaeroides.

A tyrosine ammonia-lyase (TAL) enzyme from the photosynthetic bacterium Rhodobacter sphaeroides (RsTAL) was identified, cloned and functionally expressed in Escherichia coli, where conversion of tyrosine to p-hydroxycinnamic acid (pHCA) was demonstrated. The RsTAL enzyme is implicated in production of pHCA, which serves as the cofactor for synthesis of the photoactive yellow protein (PYP) in photosynthetic bacteria. The wild type RsTAL enzyme, while accepting both tyrosine and phenylalanine as substrate, prefers tyrosine, but a serendipitous RsTAL mutant identified during PCR amplification of the RsTAL gene, demonstrates much higher preference for phenylalanine as substrate and deaminates it to produces cinnamic acid. Sequence analysis showed the presence of three mutations: Met4 --> Ile, Ile325 --> Val and Val409 --> Met in this mutant. Sequence comparison with Rhodobacter capsulatus TAL (RcTAL) shows that Val409 is conserved between RcTAL and RsTAL. Two single mutants of RsTAL, Val409 --> Met and Val 409 --> Ile, generated by site-directed mutagenesis, demonstrate greater preference for phenylalanine compared to the wild type enzyme. Our studies illustrate that relatively minor changes in the primary structure of an ammonia-lyase enzyme can significantly affect its substrate specificity.

Global gene expression profiles of the cyanobacterium Synechocystis sp. strain PCC 6803 in response to irradiation with UV-B and white light.

We developed a transcript profiling methodology to elucidate expression patterns of the cyanobacterium Synechocystis sp. strain PCC 6803 and used the technology to investigate changes in gene expression caused by irradiation with either intermediate-wavelength UV light (UV-B) or high-intensity white light. Several families of transcripts were altered by UV-B treatment, including mRNAs specifying proteins involved in light harvesting, photosynthesis, photoprotection, and the heat shock response. In addition, UV-B light induced the stringent response in Synechocystis, as indicated by the repression of ribosomal protein transcripts and other mRNAs involved in translation. High-intensity white light- and UV-B-mediated expression profiles overlapped in the down-regulation of photosynthesis genes and induction of heat shock response but differed in several other transcriptional processes including those specifying carbon dioxide uptake and fixation, the stringent response, and the induction profile of the high-light-inducible proteins. These two profile comparisons not only corroborated known physiological changes but also suggested coordinated regulation of many pathways, including synchronized induction of D1 protein recycling and a coupling between decreased phycobilisome biosynthesis and increased phycobilisome degradation. Overall, the gene expression profile analysis generated new insights into the integrated network of genes that adapts rapidly to different wavelengths and intensities of light.