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Author |
Cheung, C.; Akiyama, T.E.; Ward, J.M.; Nicol, C.J.; Feigenbaum, L.; Vinson, C.; Gonzalez, F.J. |
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Title |
Diminished hepatocellular proliferation in mice humanized for the nuclear receptor peroxisome proliferator-activated receptor alpha |
Type |
Journal Article |
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Year |
2004 |
Publication |
Cancer research |
Abbreviated Journal |
Cancer Res |
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Volume |
64 |
Issue |
11 |
Pages |
3849-3854 |
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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 |
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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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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA |
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0008-5472 |
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PMID:15172993 |
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no |
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Call Number |
refbase @ user @ |
Serial |
74 |
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Author |
Subiaul, F.; Cantlon, J.F.; Holloway, R.L.; Terrace, H.S. |
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Title |
Cognitive imitation in rhesus macaques |
Type |
Journal Article |
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Year |
2004 |
Publication |
Science (New York, N.Y.) |
Abbreviated Journal |
Science |
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Volume |
305 |
Issue |
5682 |
Pages |
407-410 |
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Keywords |
Animals; *Cognition; *Imitative Behavior; *Learning; Macaca mulatta/*physiology/psychology; Male |
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Abstract |
Experiments on imitation typically evaluate a student's ability to copy some feature of an expert's motor behavior. Here, we describe a type of observational learning in which a student copies a cognitive rule rather than a specific motor action. Two rhesus macaques were trained to respond, in a prescribed order, to different sets of photographs that were displayed on a touch-sensitive monitor. Because the position of the photographs varied randomly from trial to trial, sequences could not be learned by motor imitation. Both monkeys learned new sequences more rapidly after observing an expert execute those sequences than when they had to learn new sequences entirely by trial and error. |
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Department of Anthropology, Columbia University, New York, NY 10027, USA. subiaul@aol.com |
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1095-9203 |
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PMID:15256673 |
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no |
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Call Number |
Equine Behaviour @ team @ |
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2839 |
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Author |
Danchin, E.; Giraldeau, L.-A.; Valone, T.J.; Wagner, R.H. |
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Title |
Public information: from nosy neighbors to cultural evolution |
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Journal Article |
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Year |
2004 |
Publication |
Science (New York, N.Y.) |
Abbreviated Journal |
Science |
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Volume |
305 |
Issue |
5683 |
Pages |
487-491 |
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Keywords |
Animals; *Behavior, Animal; Cues; *Cultural Evolution; *Decision Making; Environment; Evolution; Feeding Behavior; Female; Genes; Humans; Male; Reproduction; Sexual Behavior, Animal |
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Abstract |
Psychologists, economists, and advertising moguls have long known that human decision-making is strongly influenced by the behavior of others. A rapidly accumulating body of evidence suggests that the same is true in animals. Individuals can use information arising from cues inadvertently produced by the behavior of other individuals with similar requirements. Many of these cues provide public information about the quality of alternatives. The use of public information is taxonomically widespread and can enhance fitness. Public information can lead to cultural evolution, which we suggest may then affect biological evolution. |
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Address |
U.P.M.C. CNRS-UMR7625, Bat A-7e etage-Case 237, 7 quai Saint Bernard, 75252 Paris Cedex 05, France. edanchin@snv.jussieu.fr |
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1095-9203 |
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Notes |
PMID:15273386 |
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no |
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Call Number |
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Serial |
2131 |
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Author |
Corr, J.A. |
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Title |
Nuns and monkeys: investigating the behavior of our oldest old |
Type |
Journal Article |
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Year |
2004 |
Publication |
Science of Aging Knowledge Environment : SAGE KE |
Abbreviated Journal |
Sci Aging Knowledge Environ |
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Volume |
2004 |
Issue |
41 |
Pages |
pe38 |
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Keywords |
Aged; Aged, 80 and over/*physiology; Aging/*physiology; Animals; Behavior/*physiology; Humans; Macaca mulatta |
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Abstract |
The use of nonhuman primates, particularly rhesus macaques (Macaca mulatta), as the best model for human physiological and cognitive aging is broadly accepted. Studies employing nonhuman primates to investigate behavioral changes that may occur with increasing age, however, are not common mostly because of the unavailability of appropriate subjects. Recent longitudinal human studies suggest that individual personality might play a large role in aging “successfully” and in the retention of high levels of cognition into old age. As a result of the demographic trend of increasing numbers of aged monkeys and apes in captivity, an opportunity exists to further investigate behavioral aging using the monkey model. |
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Department of Anthropology, Grand Valley State University, Allendale, MI 49401, USA. corrj@gvsu.edu |
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ISSN |
1539-6150 |
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Notes |
PMID:15483334 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2828 |
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Author |
Rietmann, T.R.; Stauffacher, M.; Bernasconi, P.; Auer, J.A.; Weishaupt, M.A. |
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Title |
The association between heart rate, heart rate variability, endocrine and behavioural pain measures in horses suffering from laminitis |
Type |
Journal Article |
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Year |
2004 |
Publication |
Journal of Veterinary Medicine. A, Physiology, Pathology, Clinical Medicine |
Abbreviated Journal |
J Vet Med A Physiol Pathol Clin Med |
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Volume |
51 |
Issue |
5 |
Pages |
218-225 |
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Keywords |
Animals; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage; Autonomic Nervous System; Behavior, Animal; Electrophysiology/*methods; Endocrine System; Female; Heart Rate; Horse Diseases/blood/drug therapy/*physiopathology; Horses; Joint Diseases/physiopathology/*veterinary; Male; Pain/physiopathology/*veterinary; Pain Measurement/*veterinary; Predictive Value of Tests |
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Abstract |
The objective of this study was to compare the stress response of horses suffering from laminitis after short- and long-term treatment with the intent to evaluate power spectral analysis of heart rate variability (HRV) for pain monitoring. Data were collected from 19 horses with acute or chronic exacerbating laminitis without known primary disease before and after treatment with non-steroidal anti-inflammatory drugs (NSAID). Recordings were carried out the day after admission to the equine hospital. Measurements were repeated on day 7 of the treatment. The recorded parameters included a clinical orthopaedic index (OLPI: Obel-grade plus hoof tester score), frequency of weight-shifting between contralateral limbs, mean beat-to-beat interval (R-R) duration, standard deviation of continuous R-R intervals, low- (LF) and high-frequency (HF) components of HRV, sympatho-vagal balance (LF/HF), and plasma concentration of cortisol, adrenalin and noradrenalin. The LF represents mainly sympathetic influences on the heart whereas HF is mediated by the parasympathetic tone. Weight-shifting and OLPI decreased significantly with treatment. The LF normalized units (n.u.) decreased after NSAID from 60.41 +/- 21.42 to 51.12 +/- 19.81 and was 49.33 +/- 22.64 on day 7, whereas HF n.u. increased from 35.07 +/- 20.02 to 43.14 +/- 18.30 and was 45.98 +/- 23.00 on day 7. Hormone levels showed no tendency to change with treatment. The OLPI was only correlated with LF/HF, LF and HF (R = 0.57, 0.55 and -0.54 respectively). Significant negative correlations existed between HFn.u. and weight-shifting frequency (R = -0.37), HFn.u. and adrenalin (R = -0.47), and HFn.u. and noradrenalin (R = 0.33). The LFn.u. only correlated positively with adrenalin. Cortisol levels were poorly associated with the other parameters. Determination of the sympatho-vagal influences on cardiac function may offer complementary information for reliable assessment of pain and may represent a valuable alternative method to catecholamine measurements. |
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Address |
Equine Hospital, Faculty of Veterinary Medicine, University of Zurich, Winterthurerstrasse 260, CH-8057 Zurich, Switzerland |
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ISSN |
0931-184X |
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Notes |
PMID:15315700 |
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no |
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Call Number |
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Serial |
1899 |
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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. |
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Title |
Enhanced acetaminophen toxicity by activation of the pregnane X receptor |
Type |
Journal Article |
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Year |
2004 |
Publication |
Toxicological sciences : an official journal of the Society of Toxicology |
Abbreviated Journal |
Toxicol Sci |
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Volume |
82 |
Issue |
2 |
Pages |
374-380 |
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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 |
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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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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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ISSN |
1096-6080 |
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Notes |
PMID:15456926 |
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no |
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Call Number |
refbase @ user @ |
Serial |
71 |
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Author |
Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. |
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Title |
PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis |
Type |
Journal Article |
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Year |
2004 |
Publication |
Carcinogenesis |
Abbreviated Journal |
Carcinogenesis |
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Volume |
25 |
Issue |
9 |
Pages |
1747-1755 |
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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 |
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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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Address |
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA |
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English |
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ISSN |
0143-3334 |
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Notes |
PMID:15073042 |
Approved |
no |
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Call Number |
refbase @ user @ |
Serial |
76 |
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Author |
Dubois, F.; Giraldeau, L.-A.; Hamilton, I.M.; Grant, J.W.A.; Lefebvre, L. |
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Title |
Distraction sneakers decrease the expected level of aggression within groups: a game-theoretic model |
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Journal Article |
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Year |
2004 |
Publication |
The American Naturalist |
Abbreviated Journal |
Am Nat |
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Volume |
164 |
Issue |
2 |
Pages |
E32-45 |
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Keywords |
*Aggression; Animals; Behavior, Animal/*physiology; Columbidae/*physiology; Competitive Behavior; Cooperative Behavior; *Game Theory; Hawks/*physiology; Models, Biological |
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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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Address |
Departement des Sciences Biologiques, Universite du Quebec a Montreal, Case postale 8888 Succursale Centre-Ville, Montreal, Quebec H3C 3P8, Canada. frede_dubois@yahoo.fr |
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English |
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ISSN |
1537-5323 |
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Notes |
PMID:15278850 |
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no |
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Call Number |
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Serial |
2130 |
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Author |
Uzawa, T.; Akiyama, S.; Kimura, T.; Takahashi, S.; Ishimori, K.; Morishima, I.; Fujisawa, T. |
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Title |
Collapse and search dynamics of apomyoglobin folding revealed by submillisecond observations of alpha-helical content and compactness |
Type |
Journal Article |
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Year |
2004 |
Publication |
Proceedings of the National Academy of Sciences of the United States of America |
Abbreviated Journal |
Proc. Natl. Acad. Sci. U.S.A. |
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Volume |
101 |
Issue |
5 |
Pages |
1171-1176 |
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Keywords |
Animals; Apoproteins/*chemistry; Circular Dichroism; Cytochromes c/chemistry; Horses; Myoglobin/*chemistry; *Protein Folding; *Protein Structure, Secondary; Scattering, Radiation |
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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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Address |
Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Nishikyo, Kyoto 615-8510, Japan |
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English |
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ISSN |
0027-8424 |
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Notes |
PMID:14711991 |
Approved |
no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
3779 |
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Author |
Mellor, P.S.; Hamblin, C. |
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Title |
African horse sickness |
Type |
Journal Article |
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Year |
2004 |
Publication |
Veterinary Research |
Abbreviated Journal |
Vet Res |
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Volume |
35 |
Issue |
4 |
Pages |
445-466 |
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Keywords |
African Horse Sickness/epidemiology/*prevention & control/*transmission/virology; African horse sickness virus/pathogenicity; Animals; Culicidae; Europe/epidemiology; Horses; Insect Vectors |
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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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Institute for Animal Health, Department of Arbovirology, Pirbright Laboratory, Ash Rd., Pirbright, Woking, Surrey, GU24 0NF, United Kingdom. philip.mellor@bbsrc.ac.uk |
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English |
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0928-4249 |
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PMID:15236676 |
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Equine Behaviour @ team @ |
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2358 |
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