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Guo, G. L., Moffit, J. S., Nicol, C. J., Ward, J. M., Aleksunes, L. A., Slitt, A. L., et al. (2004). Enhanced acetaminophen toxicity by activation of the pregnane X receptor. Toxicol Sci, 82(2), 374–380.
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.
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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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Dubois, F., Giraldeau, L. - A., Hamilton, I. M., Grant, J. W. A., & Lefebvre, L. (2004). Distraction sneakers decrease the expected level of aggression within groups: a game-theoretic model. Am Nat, 164(2), E32–45.
Abstract: Hawk-dove games have been extensively used to predict the conditions under which group-living animals should defend their resources against potential usurpers. Typically, game-theoretic models on aggression consider that resource defense may entail energetic and injury costs. However, intruders may also take advantage of owners who are busy fighting to sneak access to unguarded resources, imposing thereby an additional cost on the use of the escalated hawk strategy. In this article we modify the two-strategy hawk-dove game into a three-strategy hawk-dove-sneaker game that incorporates a distraction-sneaking tactic, allowing us to explore its consequences on the expected level of aggression within groups. Our model predicts a lower proportion of hawks and hence lower frequencies of aggressive interactions within groups than do previous two-strategy hawk-dove games. The extent to which distraction sneakers decrease the frequency of aggression within groups, however, depends on whether they search only for opportunities to join resources uncovered by other group members or for both unchallenged resources and opportunities to usurp.
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Uzawa, T., Akiyama, S., Kimura, T., Takahashi, S., Ishimori, K., Morishima, I., et al. (2004). Collapse and search dynamics of apomyoglobin folding revealed by submillisecond observations of alpha-helical content and compactness. Proc. Natl. Acad. Sci. U.S.A., 101(5), 1171–1176.
Abstract: The characterization of protein folding dynamics in terms of secondary and tertiary structures is important in elucidating the features of intraprotein interactions that lead to specific folded structures. Apomyoglobin (apoMb), possessing seven helices termed A-E, G, and H in the native state, has a folding intermediate composed of the A, G, and H helices, whose formation in the submillisecond time domain has not been clearly characterized. In this study, we used a rapid-mixing device combined with circular dichroism and small-angle x-ray scattering to observe the submillisecond folding dynamics of apoMb in terms of helical content (f(H)) and radius of gyration (R(g)), respectively. The folding of apoMb from the acid-unfolded state at pH 2.2 was initiated by a pH jump to 6.0. A significant collapse, corresponding to approximately 50% of the overall change in R(g) from the unfolded to native conformation, was observed within 300 micros after the pH jump. The collapsed intermediate has a f(H) of 33% and a globular shape that involves >80% of all its atoms. Subsequently, a stepwise helix formation was detected, which was interpreted to be associated with a conformational search for the correct tertiary contacts. The characterized folding dynamics of apoMb indicates the importance of the initial collapse event, which is suggested to facilitate the subsequent conformational search and the helix formation leading to the native structure.
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Mellor, P. S., & Hamblin, C. (2004). African horse sickness. Vet Res, 35(4), 445–466.
Abstract: African horse sickness virus (AHSV) causes a non-contagious, infectious insect-borne disease of equids and is endemic in many areas of sub-Saharan Africa and possibly Yemen in the Arabian Peninsula. However, periodically the virus makes excursions beyond its endemic areas and has at times extended as far as India and Pakistan in the east and Spain and Portugal in the west. The vectors are certain species of Culicoides biting midge the most important of which is the Afro-Asiatic species C. imicola. This paper describes the effects that AHSV has on its equid hosts, aspects of its epidemiology, and present and future prospects for control. The distribution of AHSV seems to be governed by a number of factors including the efficiency of control measures, the presence or absence of a long term vertebrate reservoir and, most importantly, the prevalence and seasonal incidence of the major vector which is controlled by climate. However, with the advent of climate-change the major vector, C. imicola, has now significantly extended its range northwards to include much of Portugal, Spain, Italy and Greece and has even been recorded from southern Switzerland. Furthermore, in many of these new locations the insect is present and active throughout the entire year. With the related bluetongue virus, which utilises the same vector species of Culicoides this has, since 1998, precipitated the worst outbreaks of bluetongue disease ever recorded with the virus extending further north in Europe than ever before and apparently becoming endemic in that continent. The prospects for similar changes in the epidemiology and distribution of AHSV are discussed.
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Harman, F. S., Nicol, C. J., Marin, H. E., Ward, J. M., Gonzalez, F. J., & Peters, J. M. (2004). Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis. Nat Med, 10(5), 481–483.
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.
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Vokey, J. R., Rendall, D., Tangen, J. M., Parr, L. A., & de Waal, F. B. M. (2004). Visual kin recognition and family resemblance in chimpanzees (Pan troglodytes). J Comp Psychol, 118(2), 194–199.
Abstract: The male-offspring biased visual kin recognition in chimpanzees (Pan troglodytes) reported by L. A. Parr and F. B. M. de Waal (1999) was replicated with human (Homo sapiens) participants and a principal components analysis (PCA) of pixel maps of the chimpanzee face photos. With the same original materials and methods, both humans and the PCA produced the same asymmetry in kin recognition as found with the chimpanzees. The PCA suggested that the asymmetry was a function of differences in the distribution of global characteristics associated with the framing of the faces in the son and daughter test sets. Eliminating potential framing biases, either by cropping the photos tightly to the faces or by rebalancing the recognition foils, eliminated the asymmetry but not human participants' ability to recognize chimpanzee kin.
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Flack, J. C., Jeannotte, L. A., & de Waal, F. B. M. (2004). Play signaling and the perception of social rules by juvenile chimpanzees (Pan troglodytes). J Comp Psychol, 118(2), 149–159.
Abstract: Prescriptive social rules are enforced statistical regularities. The authors investigated whether juvenile chimpanzees (Pan troglodytes) recognize and use enforced statistical regularities to guide dyadic play behavior. They hypothesized (a) that proximity of adults, especially mothers of younger play partners, to play bouts will increase the play signaling of older partners and (b) that when juvenile-juvenile play bouts occur in proximity to adults, older partners will play at a lower intensity than when no adults are present. They found that older and younger partners increase their play signaling in the presence of the mothers of younger partners, particularly as the intensity of play bouts increases. In contrast to their hypothesis, older partners played more roughly when the mothers of younger partners were in proximity. These results suggest that juvenile chimpanzees increase play signaling to prevent termination of the play bouts by mothers of younger partners.
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Brosnan, S. F., & de Waal, F. B. M. (2004). Socially learned preferences for differentially rewarded tokens in the brown capuchin monkey (Cebus apella). J Comp Psychol, 118(2), 133–139.
Abstract: Social learning is assumed to underlie traditions, yet evidence indicating social learning in capuchin monkeys (Cebus apella), which exhibit traditions, is sparse. The authors tested capuchins for their ability to learn the value of novel tokens using a previously familiar token-exchange economy. Capuchins change their preferences in favor of a token worth a high-value food reward after watching a conspecific model exchange 2 differentially rewarded tokens, yet they fail to develop a similar preference after watching tokens paired with foods in the absence of a conspecific model. They also fail to learn that the value of familiar tokens has changed. Information about token value is available in all situations, but capuchins seem to pay more attention in a social situation involving novel tokens.
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Beran, M. J., Pate, J. L., Washburn, D. A., & Rumbaugh, D. M. (2004). Sequential responding and planning in chimpanzees (Pan troglodytes) and rhesus macaques (Macaca mulatta). J Exp Psychol Anim Behav Process, 30(3), 203–212.
Abstract: Chimpanzees (Pan troglodytes) and rhesus macaques (Macaca mulatta) selected either Arabic numerals or colored squares on a computer monitor in a learned sequence. On shift trials, the locations of 2 stimuli were interchanged at some point. More errors were made when this interchange occurred for the next 2 stimuli to be selected than when the interchange was for stimuli later in the sequence. On mask trials, all remaining stimuli were occluded after the 1st selection. Performance exceeded chance levels for only 1 selection after these masks were applied. There was no difference in performance for either stimulus type (numerals or colors). The data indicated that the animals planned only the next selection during these computerized tasks as opposed to planning the entire response sequence.
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