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Author Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. doi  openurl
  Title Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide Type
  Year 2005 Publication The Journal of pharmacology and experimental therapeutics Abbreviated Journal J Pharmacol Exp Ther  
  Volume 312 Issue 1 Pages 69-76  
  Keywords 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 (up) Expedition Conference  
  Notes PMID:15356214 Approved  
  Call Number refbase @ user @ Serial 73  
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Author Cheung, C.; Akiyama, T.E.; Ward, J.M.; Nicol, C.J.; Feigenbaum, L.; Vinson, C.; Gonzalez, F.J. doi  openurl
  Title Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha Type
  Year 2004 Publication Cancer research Abbreviated Journal Cancer Res  
  Volume 64 Issue 11 Pages 3849-3854  
  Keywords 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 (up) Expedition Conference  
  Notes PMID:15172993 Approved  
  Call Number refbase @ user @ Serial 74  
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Author Nicol, C.J. openurl 
  Title Development, direction, and damage limitation: social learning in domestic fowl Type
  Year 2004 Publication Learning & behavior : a Psychonomic Society publication Abbreviated Journal Learn Behav  
  Volume 32 Issue 1 Pages 72-81  
  Keywords Adaptation, Psychological; Age Factors; Animals; Behavior, Animal; *Chickens; *Feeding Behavior; *Food Preferences; *Imitative Behavior; Imprinting (Psychology); *Learning; Maternal Behavior; Reinforcement (Psychology); *Social Environment; *Social Facilitation  
  Abstract This review highlights two areas of particular interest in the study of social learning in fowl. First, the role of social learning in the development of feeding and foraging behavior in young chicks and older birds is described. The role of the hen as a demonstrator and possible teacher is considered, and the subsequent social influence of brood mates and other companions on food avoidance and food preference learning is discussed. Second, the way in which work on domestic fowl has contributed to an understanding of the importance of directed social learning is examined. The well-characterized hierarchical social organization of small chicken flocks has been used to design studies which demonstrate that the probability of social transmission is strongly influenced by social relationships between birds. The practical implications of understanding the role of social learning in the spread of injurious behaviors in this economically important species are briefly considered.  
  Address Department of Clinical Veterinary Science, University of Bristol, Langford, Bristol, England. c.j.nicol@bristol.ac.uk  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1543-4494 ISBN Medium  
  Area (up) Expedition Conference  
  Notes PMID:15161142 Approved  
  Call Number refbase @ user @ Serial 75  
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Author Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. doi  openurl
  Title PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis Type
  Year 2004 Publication Carcinogenesis Abbreviated Journal Carcinogenesis  
  Volume 25 Issue 9 Pages 1747-1755  
  Keywords 9,10-Dimethyl-1,2-benzanthracene/*toxicity; Animals; DNA Primers/chemistry; Disease Susceptibility; Female; Heterozygote; Humans; Mammary Neoplasms, Experimental/chemically induced/*pathology; Mice; Ovarian Neoplasms/chemically induced/*pathology; RNA, Messenger/genetics/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms/chemically induced/*pathology; Survival Rate; Transcription Factors/genetics/*physiology; Zinc Fingers  
  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.  
  Address Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 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 0143-3334 ISBN Medium  
  Area (up) Expedition Conference  
  Notes PMID:15073042 Approved  
  Call Number refbase @ user @ Serial 76  
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Author Harman, F.S.; Nicol, C.J.; Marin, H.E.; Ward, J.M.; Gonzalez, F.J.; Peters, J.M. doi  openurl
  Title Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis Type
  Year 2004 Publication Nature medicine Abbreviated Journal Nat Med  
  Volume 10 Issue 5 Pages 481-483  
  Keywords 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 (up) Expedition Conference  
  Notes PMID:15048110 Approved  
  Call Number refbase @ user @ Serial 77  
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Author Nicol, C.J.; Potzsch, C.; Lewis, K.; Green, L.E. openurl 
  Title Matched concurrent case-control study of risk factors for feather pecking in hens on free-range commercial farms in the UK Type
  Year 2003 Publication British poultry science Abbreviated Journal Br Poult Sci  
  Volume 44 Issue 4 Pages 515-523  
  Keywords *Aggression; Analysis of Variance; Animal Husbandry/methods; Animals; Case-Control Studies; Chickens/*physiology; Feathers; Female; Multivariate Analysis; Odds Ratio; Regression Analysis; Species Specificity  
  Abstract 1. The aim of the study was to compare the management and husbandry of free-range flocks in the UK where feather pecking was either present (case) or absent (control). 2. One hundred flocks were enrolled into a concurrent case-control study: 50 where birds had recently started feather pecking, and 50 matched control flocks where birds of the same age had not started feather pecking. 3. Information was obtained from a detailed interview with the flock manager, and by direct inspection of the flock, house and range. 4. Initial univariate analyses revealed that case flocks were more likely to comprise ISA Brown than Lohmann, were more likely to be restricted from litter areas to prevent floor eggs, and were less likely to use the outside range. 5. Cluster analysis indicated that feather pecking was not associated with any particular husbandry system. 6. The only influential risk factor significant in the multivariable conditional logistic regression analysis was use of the outdoor range. The risk of feather pecking was reduced 9-fold in flocks where more than 20% of birds used the range on sunny days (odds ratio = 0.12). Use of the range was positively associated with the presence of trees and/or hedges on the range.  
  Address Department of Clinical Veterinary Science, University of Bristol, England. c.j.nicol@bris.ac.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 0007-1668 ISBN Medium  
  Area (up) Expedition Conference  
  Notes PMID:14584840 Approved  
  Call Number refbase @ user @ Serial 79  
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Author Albentosa, M.J.; Kjaer, J.B.; Nicol, C.J. openurl 
  Title Strain and age differences in behaviour, fear response and pecking tendency in laying hens Type
  Year 2003 Publication British poultry science Abbreviated Journal Br Poult Sci  
  Volume 44 Issue 3 Pages 333-344  
  Keywords Age Factors; Aggression/*physiology; Animal Husbandry; Animals; *Behavior, Animal; Breeding; Chickens/genetics/*physiology; Fear/*physiology; Feathers/*injuries; Female; Housing, Animal; Population Density; Social Behavior  
  Abstract 1. Behaviours associated with a high or low tendency to feather peck could be used as predictors of feather pecking behaviour in selective breeding programmes. This study investigated how strain and age at testing influenced responses in behavioural tests. 2. Four layer-type strains (ISA Brown, Columbian Blacktail, Ixworth and a high feather pecking (HP) and a low feather pecking (LP) line of White Leghorn) were reared in 6 same-strain/line pens of 8 birds from one day old. Birds in half the pens were given an open field test, a novel object test and a test with loose feather bundles between 4 and 12 weeks of age and a tonic immobility (TI) test at 13 weeks of age. All pens were tested with fixed feather bundles at 26 weeks, and undisturbed behaviour in the home pens was videoed at 1 and 27 weeks of age. Daily records of plumage damage were used as an indicator of feather pecking activity in the home pens. 3. Strain did not influence novel object test, open field test or loose feather test behaviour, although age effects in all three tests indicated a reduction in fearfulness and/or an increase in exploratory behaviour with increasing age. 4. White Leghorns showed longer TI durations than the other strains but less pecking at fixed feather bundles than ISA Browns and Columbian Blacktails. 5. There were few associations between behaviour in the 5 different tests, indicating that birds did not have overall behavioural traits that were consistent across different contexts. This suggests hens cannot easily be categorised into different behavioural 'types', based on their test responses and casts doubt on the usefulness of tests as predictors of feather pecking.  
  Address Centre for Behavioural Biology, Division of Farm Animal Science, University of Bristol, Langford, Bristol, England. MAlbentosa@lincoln.ac.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 0007-1668 ISBN Medium  
  Area (up) Expedition Conference  
  Notes PMID:13677322 Approved  
  Call Number refbase @ user @ Serial 80  
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Author Gavrilova, O.; Haluzik, M.; Matsusue, K.; Cutson, J.J.; Johnson, L.; Dietz, K.R.; Nicol, C.J.; Vinson, C.; Gonzalez, F.J.; Reitman, M.L. doi  openurl
  Title Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass Type
  Year 2003 Publication The Journal of biological chemistry Abbreviated Journal J Biol Chem  
  Volume 278 Issue 36 Pages 34268-34276  
  Keywords Adipose Tissue/*metabolism; Animals; Blotting, Southern; Blotting, Western; Female; Hypoglycemia/genetics; Insulin Resistance/genetics; Lipid Metabolism; Liver/*metabolism; Liver Diseases/genetics/*metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; RNA/metabolism; Receptors, Cytoplasmic and Nuclear/*genetics/*physiology; Recombination, Genetic; Thiazoles/pharmacology; *Thiazolidinediones; Time Factors; Transcription Factors/*genetics/*physiology; Triglycerides/*metabolism  
  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.  
  Address Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. oksanag@bdg10.niddk.nih.gov  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0021-9258 ISBN Medium  
  Area (up) Expedition Conference  
  Notes PMID:12805374 Approved  
  Call Number refbase @ user @ Serial 81  
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Author Freire, R.; Wilkins, L.J.; Short, F.; Nicol, C.J. openurl 
  Title Behaviour and welfare of individual laying hens in a non-cage system Type
  Year 2003 Publication British poultry science Abbreviated Journal Br Poult Sci  
  Volume 44 Issue 1 Pages 22-29  
  Keywords *Animal Welfare; Animals; *Behavior, Animal; *Chickens; Female; Housing, Animal/*standards; Oviposition  
  Abstract 1. A leg band containing a transponder was fitted to 80 birds in a perchery containing 1,000 birds. 2. The transponder emitted a unique identification number when a bird walked on one of 8 flat antennae on the floor. The recording apparatus was used to measure the amount of time that each of the tagged birds spent on the slatted and littered areas in a 6-week period. 3. Some birds spent long periods of time on the slats, possibly as a means of avoiding repeated attacks. Duration on the slats was greatest in birds with the worst (as opposed to better) feather scores of the head, back and tail regions. 4. Birds that spent long periods on the slats were lighter than other birds at both 39 weeks of age and 72 weeks of age and had greater back, head and tail feather damage, consistent with these birds being victims of pecking. 5. Tagged birds received a social avoidance test outside the perchery at 39 weeks of age, which suggested that birds retreated to the slats in response to pecks rather than just to close proximity to other birds. 6. The failure to find that duration on the slats was related to anatomical indicators of stress (liver, spleen and bursa of Fabricius) suggests that retreating to the slats following pecking attenuates physiological stress responses. 7. We conclude that the provision of areas where birds in a large group can avoid pecking may improve the welfare of a minority of victimised birds.  
  Address Department of Clinical Veterinary Science, University of Bristol, Langford, Bristol, England. rkfreire@hotmail.com  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0007-1668 ISBN Medium  
  Area (up) Expedition Conference  
  Notes PMID:12737221 Approved  
  Call Number refbase @ user @ Serial 82  
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Author McGreevy, P.D.; Webster, A.J.; Nicol, C.J. openurl 
  Title Study of the behaviour, digestive efficiency and gut transit times of crib-biting horses Type
  Year 2001 Publication The Veterinary record Abbreviated Journal Vet. Rec.  
  Volume 148 Issue 19 Pages 592-596  
  Keywords 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 (up) Expedition Conference  
  Notes PMID:11386445 Approved  
  Call Number refbase @ user @ Serial 86  
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