| Records |
| 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 |
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 |
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English |
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| ISSN |
0008-5472 |
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| Notes |
PMID:15172993 |
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no |
| Call Number |
refbase @ user @ |
Serial |
74 |
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| Author |
Markman, E.M.; Abelev, M. |
| Title |
Word learning in dogs? |
Type |
Journal Article |
| Year |
2004 |
Publication |
Trends in Cognitive Sciences |
Abbreviated Journal |
Trends. Cognit. Sci. |
| Volume |
8 |
Issue |
11 |
Pages |
479-81; discussion 481 |
| Keywords |
Animals; Association Learning; Dogs; *Learning; *Verbal Learning; *Vocabulary |
| Abstract |
In a recent paper, Kaminski, Call and Fischer report pioneering research on word-learning in a dog. In this commentary we suggest ways of distinguishing referential word use from mere association. We question whether the dog is reasoning by exclusion and, if so, compare three explanations – learned heuristics, default assumptions, and pragmatic reasoning – as they apply to children and might apply to dogs. Kaminski et al.'s work clearly raises important questions about the origins and basis of word learning and social cognition. |
| Address |
Department of Psychology, Stanford University, Bldg 420, Stanford, CA 94305-2130, USA |
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English |
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| ISSN |
1364-6613 |
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| Notes |
PMID:15491899 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
274 |
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| Author |
De Sousa, R. |
| Title |
Rational Animals |
Type |
Journal Article |
| Year |
2004 |
Publication |
Croatian Journal of Philosophy |
Abbreviated Journal |
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| Volume |
4 |
Issue |
12 |
Pages |
365-386 |
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| Abstract |
I begin with a rather unpromising dispute that Nozick once had with Ian Hacking in the pages of the London Review of Books, in which both vied with one another in their enthusiasm to repudiate the thesis that some human people or peoples are closer than others to animality. I shall attempt to show that one can build, on the basis of Nozick’s discussion of rationality, a defense of the view that the capacity for language places human rationality out of reach of a comparison with animals. The difference rests, paradoxi–cally, on the human capacity for irrationality. Irrationality depends on the capacity for language, which allows the detachment of explicit thoughts from their underlying dynamic implementation; these, in turn, condition the essential disputability of principles of rationality. That is what places every human potentially—if not actually—on the other side of an unbridge–able gulf that separates us from other animals. |
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no |
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Equine Behaviour @ team @ |
Serial |
4790 |
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| Author |
Griffiths,S. W.; Brockmark, S.; Höjesjö,J.; Johnsson,J. I. |
| Title |
Coping with divided attention: the advantage of familiarity |
Type |
Journal Article |
| Year |
2004 |
Publication |
Proceedings of the Royal Society B: Biological Sciences |
Abbreviated Journal |
Proc. Roy. Soc. Lond. B Biol. Sci. |
| Volume |
271 |
Issue |
1540 |
Pages |
695-699 |
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| Abstract |
The ability of an animal to perform a task successfully is limited by the amount of attention being simultaneously focused on other activities. One way in which individuals might reduce the cost of divided attention is by preferentially focusing on the most beneficial tasks. In territorial animals where aggression is lower among familiar individuals, the decision to associate preferentially with familiar conspecifics may therefore confer advantages by allowing attention to be switched from aggression to predator vigilance and feeding. Wild juvenile brown trout were used to test the prediction that familiar fishes respond more quickly than unfamiliar fishes to a simulated predator attack. Our results confirm this prediction by demonstrating that familiar trout respond 14% faster than unfamiliar individuals to a predator attack. The results also show that familiar fishes consume a greater number of food items, foraging at more than twice the rate of unfamiliar conspecifics. To the best of our knowledge, these results provide the first evidence that familiarity–biased association confers advantages through the immediate fitness benefits afforded by faster predator–evasion responses and the long–term benefits provided by increased feeding opportunities. |
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| Notes |
10.1098/rspb.2003.2648 |
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no |
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Equine Behaviour @ team @ |
Serial |
5007 |
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| Author |
Ghirlanda, S.; Vallortigara, G. |
| Title |
The evolution of brain lateralization: a game-theoretical analysis of population structure |
Type |
Journal Article |
| Year |
2004 |
Publication |
Proceedings of the Royal Society of London. Series B: Biological Sciences |
Abbreviated Journal |
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| Volume |
271 |
Issue |
1541 |
Pages |
853-857 |
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| Abstract |
In recent years, it has become apparent that behavioural and brain lateralization at the population level is the rule rather than the exception among vertebrates. The study of these phenomena has so far been the province of neurology and neuropsychology. Here, we show how such research can be integrated with evolutionary biology to understand lateralization more fully. In particular, we address the fact that, within a species, left– and right–type individuals often occur in proportions different from one–half (e.g. hand use in humans). The traditional explanations offered for lateralization of brain function (that it may avoid unnecessary duplication of neural circuitry and reduce interference between functions) cannot account for this fact, because increased individual efficiency is unrelated to the alignment of lateralization at the population level. A further puzzle is that such an alignment may even be disadvantageous, as it makes individual behaviour more predictable to other organisms. Here, we show that alignment of the direction of behavioural asymmetries in a population can arise as an evolutionarily stable strategy when individual asymmetrical organisms must coordinate their behaviour with that of other asymmetrical organisms. Brain and behavioural lateralization, as we know it in humans and other vertebrates, may have evolved under basically ‘social’ selection pressures. |
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no |
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Equine Behaviour @ team @ |
Serial |
5345 |
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| Author |
Bugnyar, T.; Stöwe, M.; Heinrich, B. |
| Title |
Ravens, Corvus corax, follow gaze direction of humans around obstacles |
Type |
Journal Article |
| Year |
2004 |
Publication |
Proceedings of the Royal Society B: Biological Sciences |
Abbreviated Journal |
Proc. Roy. Soc. Lond. B Biol. Sci. |
| Volume |
271 |
Issue |
1546 |
Pages |
1331-1336 |
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| Abstract |
The ability to follow gaze (i.e. head and eye direction) has recently been shown for social mammals, particularly primates. In most studies, individuals could use gaze direction as a behavioural cue without understanding that the view of others may be different from their own. Here, we show that hand–raised ravens not only visually co–orient with the look–ups of a human experimenter but also reposition themselves to follow the experimenter's gaze around a visual barrier. Birds were capable of visual co–orientation already as fledglings but consistently tracked gaze direction behind obstacles not before six months of age. These results raise the possibility that sub–adult and adult ravens can project a line of sight for the other person into the distance. To what extent ravens may attribute mental significance to the visual behaviour of others is discussed. |
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| Notes |
10.1098/rspb.2004.2738 |
Approved |
no |
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Equine Behaviour @ team @ |
Serial |
5009 |
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| Author |
Cameron, E.Z. |
| Title |
Facultative adjustment of mammalian sex ratios in support of the Trivers-Willard hypothesis: evidence for a mechanism |
Type |
Journal Article |
| Year |
2004 |
Publication |
Proceedings. Biological sciences / The Royal Society |
Abbreviated Journal |
Proc Biol Sci |
| Volume |
271 |
Issue |
1549 |
Pages |
1723-1728 |
| Keywords |
Age Factors; Animals; Body Constitution; *Evolution; Female; Glucose/metabolism/physiology; Litter Size; Male; Mammals/*physiology; *Models, Biological; Reproduction/physiology; Seasons; Sex Factors; *Sex Ratio; Time Factors |
| Abstract |
Evolutionary theory predicts that mothers of different condition should adjust the birth sex ratio of their offspring in relation to future reproductive benefits. Published studies addressing variation in mammalian sex ratios have produced surprisingly contradictory results. Explaining the source of such variation has been a challenge for sex-ratio theory, not least because no mechanism for sex-ratio adjustment is known. I conducted a meta-analysis of previous mammalian sex-ratio studies to determine if there are any overall patterns in sex-ratio variation. The contradictory nature of previous results was confirmed. However, studies that investigated indices of condition around conception show almost unanimous support for the prediction that mothers in good condition bias their litters towards sons. Recent research on the role of glucose in reproductive functioning have shown that excess glucose favours the development of male blastocysts, providing a potential mechanism for sex-ratio variation in relation to maternal condition around conception. Furthermore, many of the conflicting results from studies on sex-ratio adjustment would be explained if glucose levels in utero during early cell division contributed to the determination of offspring sex ratios. |
| Address |
Mammal Research Institute, Department of Zoology and Entomology, University of Pretoria, Pretoria 0002, South Africa. ezcameron@zoology.up.ac.za |
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English |
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0962-8452 |
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| Notes |
PMID:15306293 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
413 |
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| Author |
da Costa, A.P.; Leigh, A.E.; Man, M.-S.; Kendrick, K.M. |
| Title |
Face pictures reduce behavioural, autonomic, endocrine and neural indices of stress and fear in sheep |
Type |
Journal Article |
| Year |
2004 |
Publication |
Proceedings of the Royal Society of London. Series B: Biological Sciences |
Abbreviated Journal |
Proc. R. Soc. Lond. B. |
| Volume |
271 |
Issue |
1552 |
Pages |
2077-2084 |
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| Abstract |
Faces are highly emotive stimuli and we find smiling or familiar faces both attractive and comforting, even as young babies. Do other species with sophisticated face recognition skills, such as sheep, also respond to the emotional significance of familiar faces? We report that when sheep experience social isolation, the sight of familiar sheep face pictures compared with those of goats or inverted triangles significantly reduces behavioural (activity and protest vocalizations), autonomic (heart rate) and endocrine (cortisol and adrenaline) indices of stress. They also increase mRNA expression of activity–dependent genes (c–fos and zif/268) in brain regions specialized for processing faces (temporal and medial frontal cortices and basolateral amygdala) and for emotional control (orbitofrontal and cingulate cortex), and reduce their expression in regions associated with stress responses (hypothalamic paraventricular nucleus) and fear (central and lateral amygdala). Effects on face recognition, emotional control and fear centres are restricted to the right brain hemisphere. Results provide evidence that face pictures may be useful for relieving stress caused by unavoidable social isolation in sheep, and possibly other animal species, including humans. The finding that sheep, like humans, appear to have a right brain hemisphere involvement in the control of negative emotional experiences also suggests that functional lateralization of brain emotion systems may be a general feature in mammals. |
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no |
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Equine Behaviour @ team @ |
Serial |
5354 |
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Wilkins, L.J.; Brown, S.N.; Zimmerman, P.H.; Leeb, C.; Nicol, C.J. |
| Title |
Investigation of palpation as a method for determining the prevalence of keel and furculum damage in laying hens |
Type |
Journal Article |
| Year |
2004 |
Publication |
The Veterinary record |
Abbreviated Journal |
Vet. Rec. |
| Volume |
155 |
Issue |
18 |
Pages |
547-549 |
| Keywords |
Animal Husbandry/methods; Animal Welfare; Animals; Bone and Bones/*injuries; Chickens/*injuries; Female; Fractures, Bone/diagnosis/epidemiology/*veterinary; Great Britain/epidemiology; Housing, Animal/standards; Oviposition; Palpation/methods/*veterinary; Poultry Diseases/*diagnosis/epidemiology; Prevalence; Sensitivity and Specificity |
| 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. |
| Address |
Department of Clinical Veterinary Science, University of Bristol, Bristol BS40 5DU |
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English |
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Edition |
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| ISSN |
0042-4900 |
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| Notes |
PMID:15559420 |
Approved |
no |
| Call Number |
refbase @ user @ |
Serial |
70 |
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| Author |
Guo, G.L.; Moffit, J.S.; Nicol, C.J.; Ward, J.M.; Aleksunes, L.A.; Slitt, A.L.; Kliewer, S.A.; Manautou, J.E.; Gonzalez, F.J. |
| Title |
Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
Type |
Journal Article |
| Year |
2004 |
Publication |
Toxicological sciences : an official journal of the Society of Toxicology |
Abbreviated Journal |
Toxicol Sci |
| Volume |
82 |
Issue |
2 |
Pages |
374-380 |
| Keywords |
Acetaminophen/pharmacokinetics/*toxicity; Analgesics, Non-Narcotic/pharmacokinetics/*toxicity; Animals; Aryl Hydrocarbon Hydroxylases/biosynthesis; Biotransformation; Blotting, Northern; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP3A; Membrane Proteins; Mice; Mice, Knockout; Oxidoreductases, N-Demethylating/biosynthesis; Pregnenolone Carbonitrile/pharmacology; Receptors, Cytoplasmic and Nuclear/*drug effects; Receptors, Steroid/*drug effects; Sulfhydryl Compounds/metabolism |
| 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. |
| Address |
Laboratory of Metabolism, CCR, NCI, NIH, Bethesda, Maryland 20892, USA |
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English |
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Edition |
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1096-6080 |
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| Notes |
PMID:15456926 |
Approved |
no |
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refbase @ user @ |
Serial |
71 |
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