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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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Gavrilova, O., Haluzik, M., Matsusue, K., Cutson, J. J., Johnson, L., Dietz, K. R., et al. (2003). Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass. J Biol Chem, 278(36), 34268–34276.
Abstract: Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that mediates the antidiabetic effects of thiazolidinediones. PPAR gamma is present in adipose tissue and becomes elevated in fatty livers, but the roles of specific tissues in thiazolidinedione actions are unclear. We studied the function of liver PPAR gamma in both lipoatrophic A-ZIP/F-1 (AZIP) and wild type mice. In AZIP mice, ablation of liver PPAR gamma reduced the hepatic steatosis but worsened the hyperlipidemia, triglyceride clearance, and muscle insulin resistance. Inactivation of AZIP liver PPAR gamma also abolished the hypoglycemic and hypolipidemic effects of rosiglitazone, demonstrating that, in the absence of adipose tissue, the liver is a primary and major site of thiazolidinedione action. In contrast, rosiglitazone remained effective in non-lipoatrophic mice lacking liver PPAR gamma, suggesting that adipose tissue is the major site of thiazolidinedione action in typical mice with adipose tissue. Interestingly, mice without liver PPAR gamma, but with adipose tissue, developed relative fat intolerance, increased adiposity, hyperlipidemia, and insulin resistance. Thus, liver PPAR gamma regulates triglyceride homeostasis, contributing to hepatic steatosis, but protecting other tissues from triglyceride accumulation and insulin resistance.
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Cheung, C., Akiyama, T. E., Ward, J. M., Nicol, C. J., Feigenbaum, L., Vinson, C., et al. (2004). Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha. Cancer Res, 64(11), 3849–3854.
Abstract: Lipid-lowering fibrate drugs function as agonists for the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Sustained activation of PPARalpha leads to the development of liver tumors in rats and mice. However, humans appear to be resistant to the induction of peroxisome proliferation and the development of liver cancer by fibrate drugs. The molecular basis of this species difference is not known. To examine the mechanism determining species differences in peroxisome proliferator response between mice and humans, a PPARalpha-humanized mouse line was generated in which the human PPARalpha was expressed in liver under control of the tetracycline responsive regulatory system. The PPARalpha-humanized and wild-type mice responded to treatment with the potent PPARalpha ligand Wy-14643 as revealed by induction of genes encoding peroxisomal and mitochondrial fatty acid metabolizing enzymes and resultant decrease of serum triglycerides. However, surprisingly, only the wild-type mice and not the PPARalpha-humanized mice exhibited hepatocellular proliferation as revealed by elevation of cell cycle control genes, increased incorporation of 5-bromo-2'-deoxyuridine into hepatocyte nuclei, and hepatomegaly. These studies establish that following ligand activation, the PPARalpha-mediated pathways controlling lipid metabolism are independent from those controlling the cell proliferation pathways. These findings also suggest that structural differences between human and mouse PPARalpha are responsible for the differential susceptibility to the development of hepatocarcinomas observed after treatment with fibrates. The PPARalpha-humanized mice should serve as models for use in drug development and human risk assessment and to determine the mechanism of hepatocarcinogenesis of peroxisome proliferators.
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Nicol, C. J., Yoon, M., Ward, J. M., Yamashita, M., Fukamachi, K., Peters, J. M., et al. (2004). PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis. Carcinogenesis, 25(9), 1747–1755.
Abstract: Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis.
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Jeong, S., Han, M., Lee, H., Kim, M., Kim, J., Nicol, C. J., et al. (2004). Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice. Metabolism, 53(10), 1284–1289.
Abstract: Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice.
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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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Waters, A. J., Nicol, C. J., & French, N. P. (2002). Factors influencing the development of stereotypic and redirected behaviours in young horses: findings of a four year prospective epidemiological study. Equine Vet J, 34(6), 572–579.
Abstract: Stereotypies are invariant and repetitive behaviour patterns that seemingly have no function, which tend to develop in captive animals faced with insoluble problems and may be indicative of reduced welfare. A 4 year prospective study of the factors influencing the development of stereotypic and redirected behaviours (abnormal behaviour) in a population of 225 young Thoroughbred and part-Thoroughbred horses was conducted between 1995 and 1999. Abnormal behaviour affected 34.7% of the population. Multivariable analysis showed that foals of low- or middle-ranking mares were less likely to develop abnormal behaviour than foals of dominant mares (rate ratio (RR) 0.23, P<0.01; RR 0.48, P<0.01, respectively). Weaning by confinement in a stable or barn was associated with an increased rate of development of abnormal behaviour, compared with paddock-weaning (RR 2.19, P<0.05), and housing in barns, rather than at grass after weaning, was associated with a further increase (RR 2.54, P<0.01). Specific stereotypic and redirected behaviours were then considered as separate outcomes. Crib-biting was initiated by 10.5% of horses at median age 20 weeks, weaving by 4.6% of horses at median age 60 weeks, box-walking by 2.3% of horses at median age 64 weeks and wood-chewing by 30.3% of horses at median age 30 weeks. Wood-chewing developed at a lower rate in horses born to subordinate or mid-ranking mares than in horses born to dominant mares (RR 0.29, P<0.01; RR 0.41, P<0.01, respectively), and at a higher rate in horses kept in barns or stables rather than at grass after weaning (RR 4.49, P<0.001; RR 1A6, P<0.001, respectively). Feeding concentrates after weaning was associated with a 4-fold increase in the rate of development of crib-biting (RR 4.12, P = 0.02). The results of this study support the idea that simple changes in feeding, housing and weaning practices could substantially lower the incidence of abnormal behaviour in young horses.
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Nicol, C. J., Adachi, M., Akiyama, T. E., & Gonzalez, F. J. (2005). PPARgamma in endothelial cells influences high fat diet-induced hypertension. Am J Hypertens, 18(4 Pt 1), 549–556.
Abstract: BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful.
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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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