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Author Cheung, C.; Akiyama, T.E.; Ward, J.M.; Nicol, C.J.; Feigenbaum, L.; Vinson, C.; Gonzalez, F.J.
Title Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha Type Journal Article
Year 2004 Publication Cancer research Abbreviated Journal Cancer Res
Volume 64 Issue 11 Pages 3849-3854
Keywords (up) Animals; Anticholesteremic Agents/pharmacology; Carcinogens/pharmacology; Cell Division; DNA Replication/drug effects; Fatty Acids/metabolism; Hepatocytes/cytology/drug effects/metabolism/*physiology; Humans; Mice; Mice, Transgenic; Oxidation-Reduction; Peroxisome Proliferators/pharmacology; Pyrimidines/pharmacology; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Species Specificity; Transcription Factors/genetics/*physiology
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.
Address Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0008-5472 ISBN Medium
Area Expedition Conference
Notes PMID:15172993 Approved no
Call Number refbase @ user @ Serial 74
Permanent link to this record
 
 
Author Harman, F.S.; Nicol, C.J.; Marin, H.E.; Ward, J.M.; Gonzalez, F.J.; Peters, J.M.
Title Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis Type Journal Article
Year 2004 Publication Nature medicine Abbreviated Journal Nat Med
Volume 10 Issue 5 Pages 481-483
Keywords (up) Animals; Azoxymethane/toxicity; Colonic Neoplasms/etiology/genetics/*prevention & control; Colonic Polyps/etiology/genetics/pathology/prevention & control; Disease Models, Animal; Mice; Mice, Knockout; Mice, Mutant Strains; Phenotype; Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*physiology; Transcription Factors/deficiency/genetics/*physiology
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.
Address Department of Veterinary Science and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. jmp21@psu.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1078-8956 ISBN Medium
Area Expedition Conference
Notes PMID:15048110 Approved no
Call Number refbase @ user @ Serial 77
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Author McGreevy, P.D.; Webster, A.J.; Nicol, C.J.
Title Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses Type Journal Article
Year 2001 Publication The Veterinary record Abbreviated Journal Vet. Rec.
Volume 148 Issue 19 Pages 592-596
Keywords (up) Animals; Behavior, Animal/*physiology; Case-Control Studies; *Digestion; *Gastrointestinal Motility/drug effects; Horse Diseases/*physiopathology; Horses/*physiology/psychology; Male; Stereotyped Behavior/*physiology; Sulfapyridine/blood; Sulfasalazine/diagnostic use/pharmacology
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.
Address Department of Clinical Veterinary Science, University of Bristol, Langford
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0042-4900 ISBN Medium
Area Expedition Conference
Notes PMID:11386445 Approved no
Call Number refbase @ user @ Serial 86
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Author Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S.
Title Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide Type Journal Article
Year 2005 Publication The Journal of pharmacology and experimental therapeutics Abbreviated Journal J Pharmacol Exp Ther
Volume 312 Issue 1 Pages 69-76
Keywords (up) Animals; Cell Line; Gene Expression/drug effects; Macrophages/drug effects/metabolism; Mice; Mice, Inbred C57BL; Nitric Oxide/*metabolism; Nitric Oxide Synthase/*metabolism; Nitric Oxide Synthase Type II; PPAR delta/metabolism; PPAR gamma/*agonists/deficiency; Thiazolidinediones/pharmacology
Abstract Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 microM, whereas their binding affinity for PPARgamma is in the nanomolar range. The specificity of synthetic PPARgamma agonists for PPARgamma at the concentrations necessary for anti-inflammatory effects is thus in question. We report that PPARgamma is not necessary for the inhibition of iNOS by synthetic PPARgamma agonists. RAW 264.7 macrophages possess little PPARgamma, yet lipopolysaccharide (LPS)/interferon (IFN)gamma-induced iNOS was inhibited by synthetic PPARgamma agonists at 20 microM. Endogenous PPARgamma was inhibited by the transfection of a dominant-negative PPARgamma construct into murine mesangial cells. In the transfected cells, synthetic PPARgamma agonists inhibited iNOS production at 10 microM, similar to nontransfected cells. Using cells from PPARgamma Cre/lox conditional knockout mice, baseline and LPS/IFNgamma-induced nitric oxide levels were higher in macrophages lacking PPARgamma versus controls. However, synthetic PPARgamma agonists inhibited iNOS at 10 microM in the PPARgamma-deficient cells, similar to macrophages from wild-type mice. These results indicate that PPARgamma is not necessary for inhibition of iNOS expression by synthetic PPARgamma agonists at concentrations over 10 microM. Intrinsic PPARgamma function, in the absence of synthetic agonists, however, may play a role in inflammatory modulation.
Address Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0022-3565 ISBN Medium
Area Expedition Conference
Notes PMID:15356214 Approved no
Call Number refbase @ user @ Serial 73
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Author McGreevy, P.D.; Richardson, J.D.; Nicol, C.J.; Lane, J.G.
Title Radiographic and endoscopic study of horses performing an oral based stereotypy Type Journal Article
Year 1995 Publication Equine veterinary journal Abbreviated Journal Equine Vet J
Volume 27 Issue 2 Pages 92-95
Keywords (up) Animals; Endoscopy/*veterinary; Esophagus/physiopathology/radiography; Female; Fluoroscopy/veterinary; Horse Diseases/physiopathology/*psychology/radiography; Horses; Male; Pharynx/physiopathology/radiography; *Stereotyped Behavior; Video Recording
Abstract There is confusion in the veterinary literature concerning the definition of oral based stereotypies in the horse. This study reports the use of fluoroscopy and endoscopy during cribbiting/wind-sucking in afflicted horses. This permitted observations of movements of the pharyngeal and oesophageal tissues and of the air column within during the stereotypic behaviour. The findings reported show that the sequence of events during crib-biting/wind-sucking is not related to deglutition and that air is not swallowed to the stomach. Transient dilation of the upper oesophagus was recorded and the characteristic noise of wind-sucking coincided with the in-rush of air through the cricopharynx. The oesophageal distension was relieved when the air returned to the pharynx although small quantities passed caudally. It is proposed that the role of contraction of the strap muscles of the neck is to create a pressure gradient in the soft tissues surrounding the oesophagus which provokes movement of air from the pharynx into the oesophagus. The findings suggest that the definitions currently used in the sale of horses are in need of revision.
Address Department of Clinical Veterinary Science, University of Bristol, Langford, UK
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0425-1644 ISBN Medium
Area Expedition Conference
Notes PMID:7607156 Approved no
Call Number refbase @ user @ Serial 90
Permanent link to this record
 
 
Author Hothersall, B.; Nicol, C.
Title Role of Diet and Feeding in Normal and Stereotypic Behaviors in Horses Type Journal Article
Year 2009 Publication Veterinary Clinics of North America: Equine Practice Abbreviated Journal Clinical Nutrition
Volume 25 Issue 1 Pages 167-181
Keywords (up) Equine behavior; Diet; Crib-biting; Stereotypy; Weaning; Tryptophan; Insulin
Abstract This article reviews the effects of diet on equine feeding behavior and feeding patterns, before considering the evidence that diet affects reactivity in horses. A growing body of work suggests that fat- and fiber-based diets may result in calmer patterns of behavior, and possible mechanisms that may underpin these effects are discussed. In contrast, there is little evidence that herbal- or tryptophan-containing supplements influence equine behavior in any measurable way. The role of diet in the development of abnormal oral behaviors, particularly the oral stereotypy crib-biting, is also reviewed, and suggestions for future work are presented.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0749-0739 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number Equine Behaviour @ team @ Serial 4945
Permanent link to this record
 
 
Author Giles, S.L.; Nicol, C.J.; Harris, P.A.; Rands, S.A.
Title Dominance rank is associated with body condition in outdoor-living domestic horses (Equus caballus) Type Journal Article
Year 2015 Publication Applied Animal Behaviour Science Abbreviated Journal
Volume Issue Pages
Keywords (up) Equine; fatness; obesity; social behaviour; displacement
Abstract Abstract The aim of our study was to explore the association between dominance rank and body condition in outdoor group-living domestic horses, Equus caballus. Social interactions were recorded using a video camera during a feeding test, applied to 203 horses in 42 herds. Dominance rank was assigned to 194 individuals. The outcome variable body condition score (BCS) was recorded using a 9-point scale. The variables age and height were recorded and considered as potential confounders or effect modifiers. Results were analysed using multivariable linear and logistic regression techniques, controlling for herd group as a random effect. More dominant (p = 0.001) individuals generally had a higher body condition score (p = 0.001) and this association was entirely independent of age and height. In addition, a greater proportion of dominant individuals fell into the obese category (BCS >= 7/9, p = 0.005). There were more displacement encounters and a greater level of interactivity in herds that had less variation in age and height, lending strength to the hypothesis that phenotypic variation may aid cohesion in group-living species. In addition there was a strong quadratic relationship between age and dominance rank (p < 0.001), where middle-aged individuals were most likely to be dominant. These results are the first to link behavioural predictors to body condition and obesity status in horses and should prompt the future consideration of behavioural and social factors when evaluating clinical disease risk in group-living animals.
Address
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Language Summary Language Original Title
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Series Volume Series Issue Edition
ISSN 0168-1591 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number Equine Behaviour @ team @ Giles2015 Serial 5864
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Author Nicol, C.J.; Badnell-Waters, A.J.; Bice, R.; Kelland, A.; Wilson, A.D.; Harris, P.A.
Title The effects of diet and weaning method on the behaviour of young horses Type Journal Article
Year 2005 Publication Applied Animal Behaviour Science Abbreviated Journal Appl. Anim. Behav. Sci.
Volume 95 Issue 3-4 Pages 205-221
Keywords (up) Horse; Diet; Weaning; Temperament test
Abstract The effects of diet on horse behaviour have not previously been quantified in detail. In this study, we examined the behaviour of 17 foals from the age of 2 to 40 weeks. Each foal received either a starch and sugar (SS) diet or a fat and fibre (FF) diet. The two diets contained similar digestible energy, crude protein and micronutrients, but differed in the fat and non-structural carbohydrate balance. The baseline behaviour of the foals was observed every 2 weeks by focal animal sampling. Additional behavioural observations were conducted when the foals were weaned by one of two methods. Approximately 2 months after weaning, the temperament and tractability of the young horses was assessed using standardised tests. Responses to a novel object, to a novel person, and during a handling test were observed and quantified. Horses grew well on both diets with no apparent effects of diet on growth rate or baseline behaviour. Immediately after weaning, horses receiving the FF diet cantered less frequently (F = 5.10; p < 0.05), for a shorter duration (F = 7.23; p < 0.05) and appeared to be more settled. Foals that were barn-weaned appeared more stressed than foals that were paddock-weaned. In the temperament tests, horses receiving the FF diet spent significantly more time investigating (F = 6.78; p < 0.05), and less time looking at (F = 7.93; p < 0.05), the novel object than horses receiving the SS diet. They also spent less time walking away from the novel person (F = 5.16; p < 0.05) and their time taken to complete the handling test was significantly lower (F = 8.72; p = 0.01). Overall, the horses that received the FF diet appeared less distressed immediately after weaning and seemed calmer and more inquisitive during a range of temperament tests.
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Notes Approved no
Call Number Equine Behaviour @ team @ Serial 3642
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Author Søndergaard, E.; Jensen, M.B.; Nicol, C.J.
Title Motivation for social contact in horses measured by operant conditioning Type Journal Article
Year Publication Applied Animal Behaviour Science Abbreviated Journal Appl. Anim. Behav. Sci.
Volume In Press, Corrected Proof Issue Pages
Keywords (up) Horse; Housing; Social behaviour; Operant conditioning; Motivation
Abstract Although horses are social animals they are often housed individually with limited social contact to other horses and this may compromise their welfare. The present study included eight young female horses and investigated the strength of motivation for access to full social contact, head contact and muzzle contact, respectively, to a familiar companion horse. Horses were housed individually next to their companion horse and separations between pens prevented physical contact. During daily test sessions horses were brought to a test area where they could access an arena allowing social contact. Arena access during 3 min was given after completion of a predetermined number of responses on a panel. Fixed ratios (FR) of 8, 16, 24, 32 and 40 responses per arena access were applied in a random order, one per daily test session, within each test week (Monday to Friday), and the number of rewards per daily test session was recorded. All horses could access all three types of social contact in a cross-over design, and an empty arena was used as control. Motivational strength was assessed using elasticity of demand functions, which were estimated based on the number of rewards earned and FR. Elasticities of demand for the three types of social contact were low (-0.20), and not significantly different, although increasing FR still resulted in a decrease in rewards obtained for all three types of social contact (P < 0.001). Across FR-levels horses earned more rewards for social contact than for an empty arena, as shown by much higher intercept values (2.51 vs. 0.99; P < 0.001). However, the elasticity of demand for infrequent access to an empty arena (-0.08) was lower than for social contact (P < 0.01) and not significantly different from zero (P = 0.07). Horses performed more social behaviour the lesser the restriction on social contact (full > head > muzzle). However, the finding that horses showed a similar and high motivation for all three types of social contact suggests that they are valued equally highly in a situation where the alternative is no social contact.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0168-1591 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number Equine Behaviour @ team @ Serial 5388
Permanent link to this record
 
 
Author Søndergaard, E.; Jensen, M.B.; Nicol, C.J.
Title Motivation for social contact in horses measured by operant conditioning Type Journal Article
Year 2011 Publication Applied Animal Behaviour Science Abbreviated Journal Appl. Anim. Behav. Sci.
Volume 132 Issue 3-4 Pages 131-137
Keywords (up) Horse; Housing; Social behaviour; Operant conditioning; Motivation
Abstract Although horses are social animals they are often housed individually with limited social contact to other horses and this may compromise their welfare. The present study included eight young female horses and investigated the strength of motivation for access to full social contact, head contact and muzzle contact, respectively, to a familiar companion horse. Horses were housed individually next to their companion horse and separations between pens prevented physical contact. During daily test sessions horses were brought to a test area where they could access an arena allowing social contact. Arena access during 3 min was given after completion of a predetermined number of responses on a panel. Fixed ratios (FR) of 8, 16, 24, 32 and 40 responses per arena access were applied in a random order, one per daily test session, within each test week (Monday to Friday), and the number of rewards per daily test session was recorded. All horses could access all three types of social contact in a cross-over design, and an empty arena was used as control. Motivational strength was assessed using elasticity of demand functions, which were estimated based on the number of rewards earned and FR. Elasticities of demand for the three types of social contact were low (-0.20), and not significantly different, although increasing FR still resulted in a decrease in rewards obtained for all three types of social contact (P < 0.001). Across FR-levels horses earned more rewards for social contact than for an empty arena, as shown by much higher intercept values (2.51 vs. 0.99; P < 0.001). However, the elasticity of demand for infrequent access to an empty arena (-0.08) was lower than for social contact (P < 0.01) and not significantly different from zero (P = 0.07). Horses performed more social behaviour the lesser the restriction on social contact (full > head > muzzle). However, the finding that horses showed a similar and high motivation for all three types of social contact suggests that they are valued equally highly in a situation where the alternative is no social contact.
Address
Corporate Author Thesis
Publisher Place of Publication Editor
Language Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0168-1591 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number Equine Behaviour @ team @ Serial 5410
Permanent link to this record