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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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English |
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0008-5472 |
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PMID:15172993 |
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Call Number |
refbase @ user @ |
Serial |
74 |
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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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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA |
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0143-3334 |
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Notes |
PMID:15073042 |
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no |
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Call Number |
refbase @ user @ |
Serial |
76 |
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Author |
Ruggieri, V. |
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Title |
The running horse stops: the hypothetical role of the eyes in imagery of movement |
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Journal Article |
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Year |
1999 |
Publication |
Perceptual and motor skills |
Abbreviated Journal |
Percept Mot Skills |
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Volume |
89 |
Issue |
3 Pt 2 |
Pages |
1088-1092 |
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Keywords |
Adult; Cerebral Cortex/physiology; Eye Movements/*physiology; Female; Functional Laterality/physiology; Head/physiology; Humans; *Imagination; Models, Neurological; *Motion Perception; Movement/physiology; *Ocular Physiology; *Optical Illusions; Posture/physiology |
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Abstract |
To examine the hypothetical role of the eyes in visual mental imagery of movement 72 undergraduate women students in psychology were asked to imagine a running horse and then to produce the same mental image without moving the eyes and the head. In 59% of the subjects interesting modifications of the imagined movement appeared: 37% observed an inhibition of the movement and 19% an evident slowing up of the moving figure. The interpretation of this result was made by hypothesizing that the eyes are concretely involved in visual imagery processes. |
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University of Rome La Sapienza |
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0031-5125 |
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Notes |
PMID:10710755 |
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no |
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Call Number |
refbase @ user @ |
Serial |
94 |
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Author |
Hendricks, J.C.; Morrison, A.R. |
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Title |
Normal and abnormal sleep in mammals |
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Journal Article |
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Year |
1981 |
Publication |
Journal of the American Veterinary Medical Association |
Abbreviated Journal |
J Am Vet Med Assoc |
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Volume |
178 |
Issue |
2 |
Pages |
121-126 |
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Keywords |
Animals; Cat Diseases/physiopathology; Cats; Cattle; Dog Diseases/physiopathology; Dogs; Dreams; Horses/physiology; Humans; Narcolepsy/physiopathology/veterinary; Sleep/*physiology; Sleep Apnea Syndromes/physiopathology/veterinary; Sleep Disorders/physiopathology/*veterinary; Sleep, REM/physiology |
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0003-1488 |
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Notes |
PMID:7204232 |
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no |
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Call Number |
refbase @ user @ |
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101 |
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Author |
Alexander, F.; Davies, M.E. |
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Title |
Studies on vitamin B12 in the horse |
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Journal Article |
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Year |
1969 |
Publication |
The British veterinary journal |
Abbreviated Journal |
Br. Vet. J. |
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Volume |
125 |
Issue |
4 |
Pages |
169-176 |
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Keywords |
Animals; Biological Assay; Cattle; Chickens; Feces/analysis; Horses/*metabolism; Humans; Lactobacillus/metabolism; Rabbits; Rats; Sheep; Urine/analysis; Vitamin B 12/*analysis |
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0007-1935 |
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PMID:5814055 |
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refbase @ user @ |
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116 |
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Author |
Moses, S.N.; Villate, C.; Ryan, J.D. |
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Title |
An investigation of learning strategy supporting transitive inference performance in humans compared to other species |
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Journal Article |
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Year |
2006 |
Publication |
Neuropsychologia |
Abbreviated Journal |
Neuropsychologia |
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Volume |
44 |
Issue |
8 |
Pages |
1370-1387 |
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Keywords |
Adult; Analysis of Variance; Association Learning/*physiology; *Cognition; *Concept Formation; Female; Humans; *Logic; Male; Pattern Recognition, Visual/physiology; Photic Stimulation/methods; Reaction Time/physiology |
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Abstract |
Generalizations about neural function are often drawn from non-human animal models to human cognition, however, the assumption of cross-species conservation may sometimes be invalid. Humans may use different strategies mediated by alternative structures, or similar structures may operate differently within the context of the human brain. The transitive inference problem, considered a hallmark of logical reasoning, can be solved by non-human species via associative learning rather than logic. We tested whether humans use similar strategies to other species for transitive inference. Results are crucial for evaluating the validity of widely accepted assumptions of similar neural substrates underlying performance in humans and other animals. Here we show that successful transitive inference in humans is unrelated to use of associative learning strategies and is associated with ability to report the hierarchical relationship among stimuli. Our work stipulates that cross-species generalizations must be interpreted cautiously, since performance on the same task may be mediated by different strategies and/or neural systems. |
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Address |
Rotman Research Institute, Baycrest Centre for Geriatric Care, Toronto, Canada. smoses@rotman-baycrest.on.ca |
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0028-3932 |
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Notes |
PMID:16503340 |
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no |
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Call Number |
refbase @ user @ |
Serial |
153 |
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Author |
Horner, V.; Whiten, A.; Flynn, E.; de Waal, F.B.M. |
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Title |
Faithful replication of foraging techniques along cultural transmission chains by chimpanzees and children |
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Journal Article |
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Year |
2006 |
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 |
103 |
Issue |
37 |
Pages |
13878-13883 |
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Keywords |
Animals; Child, Preschool; Humans; *Imitative Behavior; Pan troglodytes/*psychology |
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Abstract |
Observational studies of wild chimpanzees (Pan troglodytes) have revealed population-specific differences in behavior, thought to represent cultural variation. Field studies have also reported behaviors indicative of cultural learning, such as close observation of adult skills by infants, and the use of similar foraging techniques within a population over many generations. Although experimental studies have shown that chimpanzees are able to learn complex behaviors by observation, it is unclear how closely these studies simulate the learning environment found in the wild. In the present study we have used a diffusion chain paradigm, whereby a behavior is passed from one individual to the next in a linear sequence in an attempt to simulate intergenerational transmission of a foraging skill. Using a powerful three-group, two-action methodology, we found that alternative methods used to obtain food from a foraging device (“lift door” versus “slide door”) were accurately transmitted along two chains of six and five chimpanzees, respectively, such that the last chimpanzee in the chain used the same method as the original trained model. The fidelity of transmission within each chain is remarkable given that several individuals in the no-model control group were able to discover either method by individual exploration. A comparative study with human children revealed similar results. This study is the first to experimentally demonstrate the linear transmission of alternative foraging techniques by non-human primates. Our results show that chimpanzees have a capacity to sustain local traditions across multiple simulated generations. |
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Address |
Centre for Social Learning and Cognitive Evolution, School of Psychology, University of St. Andrews, Fife KY16 9JP, United Kingdom |
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ISSN |
0027-8424 |
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Notes |
PMID:16938863 |
Approved |
no |
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Call Number |
refbase @ user @ |
Serial |
159 |
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Author |
de Waal, F.B.M. |
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Title |
A century of getting to know the chimpanzee |
Type |
Journal Article |
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Year |
2005 |
Publication |
Nature |
Abbreviated Journal |
Nature |
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Volume |
437 |
Issue |
7055 |
Pages |
56-59 |
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Keywords |
Aggression; Animals; Behavior, Animal/*physiology; Competitive Behavior; Cooperative Behavior; Female; Humans; Male; Pan troglodytes/genetics/*physiology/psychology; Sexual Behavior, Animal; *Social Behavior |
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Abstract |
A century of research on chimpanzees, both in their natural habitat and in captivity, has brought these apes socially, emotionally and mentally much closer to us. Parallels and homologues between chimpanzee and human behaviour range from tool-technology and cultural learning to power politics and intercommunity warfare. Few behavioural domains have remained untouched by this increased knowledge, which has dramatically challenged the way we view ourselves. The sequencing of the chimpanzee genome will no doubt bring more surprises and insights. Humans do occupy a special place among the primates, but this place increasingly has to be defined against a backdrop of substantial similarity. |
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Address |
Living Links, Yerkes National Primate Research Center, Emory University, 954 North Gatewood Road, Atlanta, Georgia 30322, USA. dewaal@emory.edu |
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English |
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ISSN |
1476-4687 |
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Notes |
PMID:16136128 |
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no |
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Call Number |
refbase @ user @ |
Serial |
162 |
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Author |
de Waal, F.B.M. |
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Title |
How animals do business |
Type |
Journal Article |
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Year |
2005 |
Publication |
Scientific American |
Abbreviated Journal |
Sci Am |
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Volume |
292 |
Issue |
4 |
Pages |
54-61 |
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Keywords |
Animals; Attitude; *Behavior, Animal; Cebus; Cooperative Behavior; *Economics; Emotions; Fishes; Food; Humans; Pan troglodytes; Papio; Social Behavior |
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Emory University, USA |
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0036-8733 |
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Notes |
PMID:15915815 |
Approved |
no |
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Call Number |
refbase @ user @ |
Serial |
166 |
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Author |
de Waal, F.B.M. |
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Title |
Peace lessons from an unlikely source |
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Journal Article |
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Year |
2004 |
Publication |
PLoS biology |
Abbreviated Journal |
PLoS. Biol. |
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Volume |
2 |
Issue |
4 |
Pages |
E101 |
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Keywords |
Animals; Behavior; Behavior, Animal; Culture; Humans; Interpersonal Relations; Research; Social Conditions; Social Environment; United States; *Violence |
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Abstract |
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Address |
Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA. dewaal@emory.edu |
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English |
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ISSN |
1545-7885 |
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Notes |
PMID:15094805 |
Approved |
no |
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Call Number |
refbase @ user @ |
Serial |
174 |
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