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Author |
Tsong, T.Y. |
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Title |
Conformational relaxations of urea- and guanidine hydrochloride-unfolded ferricytochrome c |
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Journal Article |
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Year |
1977 |
Publication |
The Journal of Biological Chemistry |
Abbreviated Journal |
J Biol Chem |
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Volume |
252 |
Issue |
24 |
Pages  |
8778-8780 |
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Keywords |
*Cytochrome c Group; Guanidines/*pharmacology; Protein Conformation/drug effects; Spectrometry, Fluorescence; Urea/*pharmacology |
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Abstract |
Several recent studies of protein the unfolded proteins. In urea- and guanidine HCl-unfolded ferricytochrome c (horse heart), an acid-induced spin state transformation of the heme group has been detected by the heme absorptions, Trp-59 fluorescence, and the intrinsic viscosity of protein. Kinetics of this second conformational transition, by the temperature jump and stopped flow methods, are complex. One rapid reaction (tau1), pH-independent, occurs in a 50-mus range; the second reaction (tau2), in a 1-ms range, depends linearly upon pH and is faster at the alkaline side; a third reaction (tau3), in a 1-s range, shows a sigmoidal transition at pH 5.1 and is faster at the acidic side. The results are consistent with a kinetic scheme which involves protein conformational changes in the transformation of the heme coordination state. The kinetics, along with previous equilibrium studies, indicate that ligand or charge interactions within a protein molecule are not completely prohibited even in strongly denaturing conditions, such as in high concentrations of urea and guanidine HCl. Thus, local structures of peptide chain associated with these interactions can exist in the unfolded protein. |
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0021-9258 |
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PMID:200618 |
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refbase @ user @ |
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3882 |
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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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refbase @ user @ |
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74 |
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Author |
Dunn, M.F.; Branlant, G. |
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Title |
Roles of zinc ion and reduced coenzyme in horse liver alcohol dehydrogenase catalysis. The mechanism of aldehyde activation |
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Journal Article |
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Year |
1975 |
Publication |
Biochemistry |
Abbreviated Journal |
Biochemistry |
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Volume |
14 |
Issue |
14 |
Pages |
3176-3182 |
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Keywords |
*Alcohol Oxidoreductases/metabolism; Aldehydes/*pharmacology; Animals; Binding Sites; Enzyme Activation/drug effects; Horses; Hydrogen-Ion Concentration; Kinetics; Liver/enzymology; *NAD/analogs & derivatives/pharmacology; Oxidation-Reduction; Protein Binding; Spectrophotometry; Spectrophotometry, Ultraviolet; Temperature; *Zinc/pharmacology |
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1,4,5,6-Tetrahydronicotinamide adenine dinucleotide (H2NADH) has been investigated as a reduced coenzyme analog in the reaction between trans-4-N,N-dimethylaminocinnamaldehyde (I) (lambdamax 398 nm, epsilonmax 3.15 X 10-4 M-minus 1 cm-minus 1) and the horse liver alcohol dehydrogenase-NADH complex. These equilibrium binding and temperature-jump kinetic studies establish the following. (i) Substitution of H2NADH for NADH limits reaction to the reversible formation of a new chromophoric species, lambdamax 468 nm, epsilonmax 5.8 x 10-4 M-minus 1 cm-minus 1. This chromophore is demonstrated to be structurally analogous to the transient intermediate formed during the reaction of I with the enzyme-NADH complex [Dunn, M. F., and Hutchison, J. S. (1973), Biochemistry 12, 4882]. (ii) The process of intermediate formation with the enzyme-NADH complex is independent of pH over the range 6.13-10.54. Although studies were limited to the pH range 5.98-8.72, a similar pH independence appears to hold for the H2NADH system. (iii) Within the ternary complex, I is bound within van der Waal's contact distance of the coenzyme nicotinamide ring. (iv) Formation of the transient intermediate does not involve covalent modification of coenzyme. Based on these findings, we conclude that zinc ion has a Lewis acid function in facilitating the chemical activation of the aldehyde carbonyl for reduction, and that reduced coenzyme plays a noncovalent effector role in this substrate activating step. |
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0006-2960 |
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PMID:238585 |
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no |
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Call Number |
Equine Behaviour @ team @ |
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3817 |
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Author |
Houpt, K.A.; Northrup, N.; Wheatley, T.; Houpt, T.R. |
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Title |
Thirst and salt appetite in horses treated with furosemide |
Type |
Journal Article |
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Year |
1991 |
Publication |
Journal of applied physiology (Bethesda, Md. : 1985) |
Abbreviated Journal |
J Appl Physiol |
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Volume |
71 |
Issue |
6 |
Pages |
2380-2386 |
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Keywords |
Animals; Appetite/*drug effects; Blood Volume; Diuresis; Drinking/drug effects; Female; Furosemide/*pharmacology; Horses; Natriuresis; Sodium, Dietary/*administration & dosage; Thirst/*drug effects |
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Abstract |
When a preliminary experiment in sodium-replete ponies revealed an increase, but not a significant increase, in salt consumption after furosemide treatment, the experiment was repeated using sodium-deficient horses in which aldosterone levels might be expected to be elevated to test the hypothesis that a background of aldosterone is necessary for salt appetite. Ten Standardbred mares were injected intravenously with furosemide or an equivalent volume of 0.9% sodium chloride as a control to test the effect of furosemide on their salt appetite and blood constituents. Sodium intake and sodium loss in urine, as well as water intake and urine output, were measured and compared to determine accuracy of compensation for natriuresis and diuresis. Plasma protein and packed cell volume showed significant increases in response to furosemide treatment (F = 29.31, P less than 0.001 and F = 11.20, P less than 0.001, respectively). There were no significant changes in plasma sodium concentration or osmolality in response to the treatment (P greater than 0.05). The furosemide-treated horses consumed 126 +/- 14.8 g salt, significantly more than when they were given the control injection (94.5 +/- 9.8 g; t = 2.22, P = 0.05). In response to furosemide, horses lost 962 +/- 79.7 and consumed 2,170 +/- 5 meq sodium; however, compared with control, they lost 955 meq more sodium and ingested only 570 meq more sodium, so they were undercompensating for natriuresis. The furosemide-treated horses drank 9.6 +/- 0.8 kg of water, significantly more than when they received the control injection (6.4 +/- 0.8 kg; t = 6.9, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) |
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Department of Physiology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853-6401 |
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8750-7587 |
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PMID:1778936 |
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Call Number |
refbase @ user @ |
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38 |
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Author |
Jeong, S.; Han, M.; Lee, H.; Kim, M.; Kim, J.; Nicol, C.J.; Kim, B.H.; Choi, J.H.; Nam, K.-H.; Oh, G.T.; Yoon, M. |
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Title |
Effects of fenofibrate on high-fat diet-induced body weight gain and adiposity in female C57BL/6J mice |
Type |
Journal Article |
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Year |
2004 |
Publication |
Metabolism: clinical and experimental |
Abbreviated Journal |
Metabolism |
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Volume |
53 |
Issue |
10 |
Pages |
1284-1289 |
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Keywords |
Adipose Tissue/*anatomy & histology/drug effects; Animals; Antilipemic Agents/*pharmacology; Body Composition/*drug effects; Body Weight/drug effects; Dietary Fats/*pharmacology; Eating/drug effects; Fatty Acids/metabolism; Female; Gene Expression Regulation/drug effects; Leptin/metabolism; Liver/metabolism; Mice; Mice, Inbred C57BL; Ovariectomy; Procetofen/*pharmacology; RNA, Messenger/biosynthesis/genetics; Receptors, Cytoplasmic and Nuclear/biosynthesis/genetics/metabolism; Transcription Factors/biosynthesis/genetics/metabolism; Weight Gain/*drug effects |
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Our previous study suggested that fenofibrate affects obesity and lipid metabolism in a sexually dimorphic manner in part through the differential activation of hepatic peroxisome proliferator-activated receptor alpha (PPARalpha) in male and female C57BL/6J mice. To determine whether fenofibrate reduces body weight gain and adiposity in female sham-operated (Sham) and ovariectomized (OVX) C57BL/6J mice, the effects of fenofibrate on not only body weight, white adipose tissue (WAT) mass, and food intake, but also the expression of both leptin and PPARalpha target genes were measured. Compared to their respective low-fat diet-fed controls, both Sham and OVX mice exhibited increases in body weight and WAT mass when fed a high-fat diet. Fenofibrate treatment decreased body weight gain and WAT mass in OVX, but not in Sham mice. Furthermore, fenofibrate increased the mRNA levels of PPARalpha target genes encoding peroxisomal enzymes involved in fatty acid beta-oxidation, and reduced apolipoprotein C-III (apo C-III) mRNA, all of which were expressed at higher levels in OVX compared to Sham mice. However, leptin mRNA levels were found to positively correlate with WAT mass, and food intake was not changed in either OVX or Sham mice following fenofibrate treatment. These results suggest that fenofibrate differentially regulates body weight and adiposity due in part to differences in PPARalpha activation, but not to differences in leptin production, between female OVX and Sham mice. |
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Department of Life Sciences, Mokwon University, Taejon, Korea |
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0026-0495 |
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PMID:15375783 |
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no |
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Call Number |
refbase @ user @ |
Serial |
72 |
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Author |
Pierce, M.M.; Nall, B.T. |
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Title |
Coupled kinetic traps in cytochrome c folding: His-heme misligation and proline isomerization |
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Journal Article |
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Year |
2000 |
Publication |
Journal of Molecular Biology |
Abbreviated Journal |
J Mol Biol |
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Volume |
298 |
Issue |
5 |
Pages |
955-969 |
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Keywords |
Amino Acid Sequence; Amino Acid Substitution/genetics; Binding Sites; Cytochrome c Group/*chemistry/genetics/*metabolism; *Cytochromes c; Enzyme Stability/drug effects; Fluorescence; Guanidine/pharmacology; Heme/*metabolism; Histidine/genetics/*metabolism; Hydrogen-Ion Concentration; Isomerism; Kinetics; Models, Molecular; Molecular Sequence Data; Mutation/genetics; Proline/*chemistry/metabolism; Protein Conformation/drug effects; Protein Denaturation/drug effects; *Protein Folding; Protein Renaturation; Saccharomyces cerevisiae/enzymology/genetics; Sequence Alignment; Thermodynamics |
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Abstract |
The effect of His-heme misligation on folding has been investigated for a triple mutant of yeast iso-2 cytochrome c (N26H,H33N,H39K iso-2). The variant contains a single misligating His residue at position 26, a location at which His residues are found in several cytochrome c homologues, including horse, tuna, and yeast iso-1. The amplitude for fast phase folding exhibits a strong initial pH dependence. For GdnHCl unfolded protein at an initial pH<5, the observed refolding at final pH 6 is dominated by a fast phase (tau(2f)=20 ms, alpha(2f)=90 %) that represents folding in the absence of misligation. For unfolded protein at initial pH 6, folding at final pH 6 occurs in a fast phase of reduced amplitude (alpha(2f) approximately 20 %) but the same rate (tau(2f)=20 ms), and in two slower phases (tau(m)=6-8 seconds, alpha(m) approximately 45 %; and tau(1b)=16-20 seconds, alpha(1b) approximately 35 %). Double jump experiments show that the initial pH dependence of the folding amplitudes results from a slow pH-dependent equilibrium between fast and slow folding species present in the unfolded protein. The slow equilibrium arises from coupling of the His protonation equilibrium to His-heme misligation and proline isomerization. Specifically, Pro25 is predominantly in trans in the unligated low-pH unfolded protein, but is constrained in a non-native cis isomerization state by His26-heme misligation near neutral pH. Refolding from the misligated unfolded form proceeds slowly due to the large energetic barrier required for proline isomerization and displacement of the misligated His26-heme ligand. |
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Center for Biomolecular Structure, Department of Biochemistry, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA |
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0022-2836 |
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PMID:10801361 |
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no |
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Call Number |
refbase @ user @ |
Serial |
3853 |
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Author |
Pennisi, E. |
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Title |
Schizophrenia clues from monkeys |
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Year |
1997 |
Publication |
Science (New York, N.Y.) |
Abbreviated Journal |
Science |
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Volume |
277 |
Issue |
5328 |
Pages |
900 |
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Keywords |
Animals; Antipsychotic Agents/pharmacology; Behavior, Animal/drug effects; *Cercopithecus aethiops; Clozapine/pharmacology; Cognition/drug effects; *Disease Models, Animal; Dopamine/*metabolism; Excitatory Amino Acid Antagonists/pharmacology; Memory/drug effects; Phencyclidine/*pharmacology; Prefrontal Cortex/*metabolism; Schizophrenia/chemically induced/drug therapy/*metabolism; Schizophrenic Psychology |
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0036-8075 |
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PMID:9281070 |
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no |
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Equine Behaviour @ team @ |
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2844 |
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Author |
Blokland, A. |
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Title |
Reaction time responding in rats |
Type |
Journal Article |
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Year |
1998 |
Publication |
Neuroscience and Biobehavioral Reviews |
Abbreviated Journal |
Neurosci Biobehav Rev |
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Volume |
22 |
Issue |
6 |
Pages |
847-864 |
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Amphetamine/pharmacology; Animals; Behavior, Animal/drug effects/*physiology; Conditioning, Operant/drug effects/*physiology; Dopamine Uptake Inhibitors/pharmacology; Dose-Response Relationship, Drug; Male; Rats; Rats, Inbred Lew; Reaction Time/drug effects/*physiology |
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Abstract |
The use of reaction time has a great tradition in the field of human information processing research. In animal research the use of reaction time test paradigms is mainly limited to two research fields: the role of the striatum in movement initiation; and aging. It was discussed that reaction time responding can be regarded as “single behavior”, this term was used to indicate that only one behavioral category is measured, allowing a better analysis of brain-behavior relationships. Reaction time studies investigating the role of the striatum in motor functions revealed that the initiation of a behavioral response is dependent on the interaction of different neurotransmitters (viz. dopamine, glutamate, GABA). Studies in which lesions were made in different brain structures suggested that motor initiation is dependent on defined brain structures (e.g. medialldorsal striatum, prefrontal cortex). It was concluded that the use of reaction time measures can indeed be a powerful tool in studying brain-behavior relationships. However, there are some methodological constraints with respect to the assessment of reaction time in rats, as was tried to exemplify by the experiments described in the present paper. On the one hand one should try to control for behavioral characteristics of rats that may affect the validity of the parameter reaction time. On the other hand, the mean value of reaction time should be in the range of what has been reported in man. Although these criteria were not always met in several studies, it was concluded that reaction time can be validly assessed in rats. Finally, it was discussed that the use of reaction time may go beyond studies that investigate the role of the basal ganglia in motor output. Since response latency is a direct measure of information processing this parameter may provide insight into basic elements of cognition. Based on the significance of reaction times in human studies the use of this dependent variable in rats may provide a fruitful approach in studying brain-behavior relationships in cognitive functions. |
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Department of Psychology, University of Maastricht, The Netherlands |
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0149-7634 |
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Notes |
PMID:9809315 |
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no |
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Call Number |
Equine Behaviour @ team @ |
Serial |
2807 |
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Author |
Alexander, F.; Ash, R.W. |
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Title |
The effect of emotion and hormones on the concentration of glucose and eosinophils in horse blood |
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Journal Article |
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Year |
1955 |
Publication |
The Journal of physiology |
Abbreviated Journal |
J Physiol |
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Volume |
130 |
Issue |
3 |
Pages |
703-710 |
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Keywords |
Blood Glucose/*drug effects; Eosinophils/*drug effects; Leukocyte Count/*drug effects; *ACTH/effects; *BLOOD SUGAR/effect of drugs on; *EOSINOPHIL COUNT/effect of drugs on; *EPINEPHRINE/effects; *HISTAMINE/effects; *INSULIN/effects; *STRESS/experimental |
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0022-3751 |
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PMID:13278929 |
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no |
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refbase @ user @ |
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122 |
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Milgram, N.W.; Head, E.; Muggenburg, B.; Holowachuk, D.; Murphey, H.; Estrada, J.; Ikeda-Douglas, C.J.; Zicker, S.C.; Cotman, C.W. |
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Title |
Landmark discrimination learning in the dog: effects of age, an antioxidant fortified food, and cognitive strategy |
Type |
Journal Article |
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Year |
2002 |
Publication |
Neuroscience and Biobehavioral Reviews |
Abbreviated Journal |
Neurosci Biobehav Rev |
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Volume |
26 |
Issue |
6 |
Pages |
679-695 |
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Keywords |
Age Factors; Aging/*physiology; Analysis of Variance; Animals; Antioxidants/*pharmacology; Blood Chemical Analysis/methods; Cognition/*physiology; *Diet; Discrimination Learning/*drug effects/*physiology; Distance Perception/drug effects/physiology; Dogs/physiology; Female; Male; Psychomotor Performance/physiology; Retention (Psychology)/drug effects/physiology; Spatial Behavior/*drug effects/*physiology; Task Performance and Analysis; Time Factors; Vitamin E/blood |
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Abstract |
The landmark discrimination learning test can be used to assess the ability to utilize allocentric spatial information to locate targets. The present experiments examined the role of various factors on performance of a landmark discrimination learning task in beagle dogs. Experiments 1 and 2 looked at the effects of age and food composition. Experiments 3 and 4 were aimed at characterizing the cognitive strategies used in performance on this task and in long-term retention. Cognitively equivalent groups of old and young dogs were placed into either a test group maintained on food enriched with a broad-spectrum of antioxidants and mitochondrial cofactors, or a control group maintained on a complete and balanced food formulated for adult dogs. Following a wash-in period, the dogs were tested on a series of problems, in which reward was obtained when the animal responded selectively to the object closest to a thin wooden block, which served as a landmark. In Experiment 1, dogs were first trained to respond to a landmark placed directly on top of coaster, landmark 0 (L0). In the next phase of testing, the landmark was moved at successively greater distances (1, 4 or 10 cm) away from the reward object. Learning varied as a function of age group, food group, and task. The young dogs learned all of the tasks more quickly than the old dogs. The aged dogs on the enriched food learned L0 significantly more rapidly than aged dogs on control food. A higher proportion of dogs on the enriched food learned the task, when the distance was increased to 1cm. Experiment 2 showed that accuracy decreased with increased distance between the reward object and landmark, and this effect was greater in old animals. Experiment 3 showed stability of performance, despite using a novel landmark, and new locations, indicating that dogs learned the landmark concept. Experiment 4 found age impaired long-term retention of the landmark task. These results indicate that allocentric spatial learning is impaired in an age-dependent manner in dogs, and that age also affects performance when the distance between the landmark and target is increased. In addition, these results both support a role of oxidative damage in the development of age-associated cognitive dysfunction and indicate that short-term administration of a food enriched with supplemental antioxidants and mitochondrial cofactors can partially reverse the deleterious effects of aging on cognition. |
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Life Science Division, University of Toronto at Scarborough, 1265 Military Trail, Scarborough, Ont., Canada M1C 1A4. milgram@psych.utoronto.ca |
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English |
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0149-7634 |
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PMID:12479842 |
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Equine Behaviour @ team @ |
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2806 |
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