Harman, F. S., Nicol, C. J., Marin, H. E., Ward, J. M., Gonzalez, F. J., & Peters, J. M. (2004). Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Nat Med, 10(5), 481–483.
Abstract: Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemically induced mouse models, colon polyp formation was significantly greater in mice nullizygous for PPAR-delta. In contrast to previous reports suggesting that activation of PPAR-delta potentiates colon polyp formation, here we show that PPAR-delta attenuates colon carcinogenesis.
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Viry, S., Sleimen-Malkoun, R., Temprado, J. - J., Frances, J. - P., Berton, E., Laurent, M., et al. (2013). Patterns of Horse-Rider Coordination during Endurance Race: A Dynamical System Approach. PLoS ONE, 8(8), e71804 EP -.
Abstract: <p>In riding, most biomechanical studies have focused on the description of the horse locomotion in unridden condition. In this study, we draw the prospect of how the basic principles established in inter-personal coordination by the theory of <italic>Coordination Dynamics</italic> may provide a conceptual and methodological framework for understanding the horse-rider coupling. The recent development of mobile technologies allows combined horse and rider recordings during long lasting natural events such as endurance races. Six international horse-rider dyads were thus recorded during a 120 km race by using two tri-axial accelerometers placed on the horses and riders, respectively. The analysis concentrated on their combined vertical displacements. The obtained shapes and angles of Lissajous plots together with values of relative phase between horse and rider displacements at lower reversal point allowed us to characterize four coordination patterns, reflecting the use of two riding techniques per horse's gait (trot and canter). The present study shows that the concepts, methods and tools of self-organizing dynamic system approach offer new directions for understanding horse-rider coordination. The identification of the horse-rider coupling patterns constitutes a firm basis to further study the coalition of multiple constraints that determine their emergence and their dynamics in endurance race.</p>
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Wells, P. G., Bhuller, Y., Chen, C. S., Jeng, W., Kasapinovic, S., Kennedy, J. C., et al. (2005). Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species. Toxicol Appl Pharmacol, 207(2 Suppl), 354–366.
Abstract: Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk.
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Guo, G. L., Moffit, J. S., Nicol, C. J., Ward, J. M., Aleksunes, L. A., Slitt, A. L., et al. (2004). Enhanced acetaminophen toxicity by activation of the pregnane X receptor. Toxicol Sci, 82(2), 374–380.
Abstract: The pregnane X receptor (PXR) is a ligand-activated transcription factor and member of the nuclear receptor superfamily. Activation of PXR represents an important mechanism for the induction of cytochrome P450 3A (CYP3A) enzymes that can convert acetaminophen (APAP) to its toxic intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Therefore, it was hypothesized that activation of PXR plays a major role in APAP-induced hepatotoxicity. Pretreatment with the PXR activator, pregnenolone 16alpha-carbonitrile (PCN), markedly enhanced APAP-induced hepatic injury, as revealed by increased serum ALT levels and hepatic centrilobular necrosis, in wild-type but not in PXR-null mice. Further analysis showed that following PCN treatment, PXR-null mice had lower CYP3A11 expression, decreased NAPQI formation, and increased maintenance of hepatic glutathione content compared to wild-type mice. Thus, these results suggest that PXR plays a critical role in APAP-induced hepatic toxicity, probably by inducing CYP3A11 expression and hence increasing bioactivation.
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Wilkins, L. J., Brown, S. N., Zimmerman, P. H., Leeb, C., & Nicol, C. J. (2004). Investigation of palpation as a method for determining the prevalence of keel and furculum damage in laying hens. Vet. Rec., 155(18), 547–549.
Abstract: Old breaks of the keel and furculum were identified by palpation in 500 end-of-lay hens from 10 flocks housed in free-range and barn systems, and the results were compared with the results obtained by a full dissection and inspection. The method was considered to be sufficiently precise to be used as a diagnostic tool although people using it would need to be trained. The results obtained by dissection indicated that 50 to 78 per cent of the birds in the flocks had breaks of the furculum and keel, but no other breaks of bones were detected.
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Nicol, C. J., Davidson, H. P. D., Harris, P. A., Waters, A. J., & Wilson, A. D. (2002). Study of crib-biting and gastric inflammation and ulceration in young horses. Vet. Rec., 151(22), 658–662.
Abstract: Nineteen young horses that had recently started to perform the stereotypy of crib-biting were compared with 16 non-stereotypic horses for 14 weeks. After initial observations of their behaviour and an endoscopic examination of the condition of their stomachs, the horses were randomly allocated to a control or an antacid diet At the start of the trial, the stomachs of the crib-biting foals were significantly more ulcerated and inflamed than the stomachs of the normal foals. In addition, the faecal pH of the crib-biting foals (6.05) was significantly lower than that of the normal foals (6.58). The antacid diet resulted in a significant improvement in the condition of the horses' stomachs. The crib-biting behaviour declined in most of the foals, regardless of their diet, but tended to decline to a greater extent in the foals on the antacid diet.
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McGreevy, P. D., Webster, A. J., & Nicol, C. J. (2001). Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses. Vet. Rec., 148(19), 592–596.
Abstract: The spontaneous behaviour and the apparent digestibility of dry matter and fibre and transit times of digesta were compared in four normal horses and four crib-biters. A technique was developed for measuring total gut transit times (TGTT) by using single-stool analysis of the passage of radio-opaque polyethylene markers. Longer TGTT were recorded in the crib-biters than in the normal horses but the orocaecal transit times did not differ. The crib-biters rested less than the normal horses.
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McGreevy, P. D., French, N. P., & Nicol, C. J. (1995). The prevalence of abnormal behaviours in dressage, eventing and endurance horses in relation to stabling. Vet. Rec., 137(2), 36–37.
Abstract: The behaviour of horses competing in different disciplines was studied and the relationship between the time they spent out of the stable and the prevalence of abnormal behaviour was examined. The owners of dressage, eventing and endurance horses were sent a questionnaire and a total of 1101 responses were received, giving data on 1750 horses. The behaviours studied were wood-chewing, weaving, crib-biting/wind-sucking and box-walking. The reported percentage prevalences of abnormal behaviour for the dressage, eventing and endurance horses were 32.5, 30.8 and 19.5, respectively. The relationship between the time spent in the stable and the prevalence of abnormal behaviour was examined by chi 2 tests which showed that there were significant linear trends for the eventing group (P < 0.001) and the dressage group (P < 0.05). It is concluded that the time a horse spends out of the stable is related to the discipline for which it is being trained and in dressage and eventing horses the time spent in a stable is correlated with an increased risk of abnormal behaviour.
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