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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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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Herrmann, E., Melis, A. P., & Tomasello, M. (2006). Apes' use of iconic cues in the object-choice task. Anim. Cogn., 9(2), 118–130.
Abstract: In previous studies great apes have shown little ability to locate hidden food using a physical marker placed by a human directly on the target location. In this study, we hypothesized that the perceptual similarity between an iconic cue and the hidden reward (baited container) would help apes to infer the location of the food. In the first two experiments, we found that if an iconic cue is given in addition to a spatial/indexical cue – e.g., picture or replica of a banana placed on the target location – apes (chimpanzees, bonobos, orangutans, gorillas) as a group performed above chance. However, we also found in two further experiments that when iconic cues were given on their own without spatial/indexical information (iconic cue held up by human with no diagnostic spatial/indexical information), the apes were back to chance performance. Our overall conclusion is that although iconic information helps apes in the process of searching hidden food, the poor performance found in the last two experiments is due to apes' lack of understanding of the informative (cooperative) communicative intention of the experimenter.
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