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Maury, M.; Murphy, K.; Kumar, S.; Mauerer, A.; Lee, G. |
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Title |
Spray-drying of proteins: effects of sorbitol and trehalose on aggregation and FT-IR amide I spectrum of an immunoglobulin G |
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Journal Article |
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Year |
2005 |
Publication |
European Journal of Pharmaceutics and Biopharmaceutics |
Abbreviated Journal |
Eur. J. Pharm. Biopharm. |
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59 |
Issue |
2 |
Pages |
251-261 |
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Immunoglobulin; Spray-drying; Stabilization; Sorbitol; Trehalose; Water replacement |
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Abstract |
An immunoglobulin G (IgG) was spray-dried on a Büchi 190 laboratory spray-dryer at inlet and outlet air temperatures of 130 and 190°C, respectively. The IgG solution contains initially 115mg/ml IgG plus 50mg/ml sorbitol. After dialysis, at least 80% of low molecular weight component was removed. After spray-drying the dialyzed IgG and immediate redissolution of the powder, an increase in aggregates from 1 to 17% occurred. A major shift towards increase β-sheet structure was detected in the spray-dried solid, which, however, reverted to native structure on redissolution of the powder. A correlation between aggregation determined by size exclusion chromatography and alterations in secondary structure determined by Fourier transformation infra-red spectroscopy could not therefore be established. On spray-drying a non-dialyzed, sorbitol-containing IgG only some 0.7% aggregates were formed. The sorbitol is therefore evidently able to stabilize partially the IgG during the process of spray-drying. Addition of trehalose to the liquid feed produced quantitatively the same stabilizing action on the IgG during spray-drying as did the sorbitol. This finding again points towards a water replacement stabilization mechanism. The IgG spray-dried powder prepared from the dialyzed liquid feed showed continued substantial aggregation on dry storage at 25°C. This was substantially less in the non-dialyzed, sorbitol-containing spray-dried powder. Addition of trehalose to both dialyzed and non-dialyzed system produced substantial improvement in storage stability and reduction in aggregate formation in storage. The quantitative stabilizing effect of the trehalose was only slightly higher than that of the sorbitol. Taken together, these results indicate that both the sorbitol and trehalose stabilize the IgG primarily by a water replacement mechanism rather than by glassy immobilization. The relevance of this work is its questioning of the importance of the usually considered dominance of glassy stabilization of protein in dried systems of high glass transition temperature, such as trehalose. The low glass transition temperature sorbitol produces almost equal process and storage stability in this case. |
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0939-6411 |
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Equine Behaviour @ team @ |
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6515 |
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Lonsdorf, E.V. |
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Title |
Sex differences in the development of termite-fishing skills in the wild chimpanzees, Pan troglodytes schweinfurthii, of Gombe National Park, Tanzania |
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Journal Article |
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Year |
2005 |
Publication |
Animal Behaviour |
Abbreviated Journal |
Anim. Behav. |
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70 |
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3 |
Pages |
673-683 |
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By the age of 5.5 years, all of the young chimpanzees of Gombe National Park have acquired a skill known as 'termite fishing'. Termite fishing involves inserting a flexible tool made from vegetation into a termite mound and extracting the termites that attack and cling to the tool. Although tool use is a well-known phenomenon in chimpanzees, little is known about how such skills develop in the wild. Prior studies have found adult sex differences in frequency, duration and efficiency of tool-using tasks, with females scoring higher on all measures. To investigate whether these sex differences occurred in youngsters, I performed a 4-year longitudinal field study during which I observed and videotaped young chimpanzees' development of the termite-fishing behaviour. Critical elements of the skill included identifying a hole, making a tool, inserting a tool into a hole and extracting termites. These elements appeared in the same order during the development of all subjects, but females typically peaked at least a year earlier than males in their performance of the skills that precede termite fishing. In addition, young females successfully termite-fished an average of 27 months earlier than young males and were more proficient at the skill after acquisition had occurred. Furthermore, the techniques of female offspring closely resembled those of their mothers whereas the techniques of male offspring did not, suggesting that the process by which termite fishing is learned differs for male and female chimpanzees. |
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0003-3472 |
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Equine Behaviour @ team @ |
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6536 |
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Pongrácz, P.; Miklósi, Á.; Vida, V.; Csányi, V. |
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Title |
The pet dogs ability for learning from a human demonstrator in a detour task is independent from the breed and age |
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Journal Article |
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Year |
2005 |
Publication |
Applied Animal Behaviour Science |
Abbreviated Journal |
Appl. Anim. Behav. Sci. |
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90 |
Issue |
3 |
Pages |
309-323 |
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Dog; Breed differences; Social learning |
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There are many indications and much practical knowledge about the different tasks which various breeds of dogs are selected for. Correspondingly these different breeds are known to possess different physical and mental abilities. We hypothesized that commonly kept breeds will show differences in their problem solving ability in a detour task around a V-shaped fence, and also, that breed differences will affect their learning ability from a human demonstrator, who demonstrates a detour around the fence. Subjects were recruited in Hungarian pet dog schools. We compared the results of the 10 most common breeds in our sample when they were tested in the detour task without human demonstration. There was no significant difference between the latencies of detour, however, there was a trend that German Shepherd dogs were the quickest and Giant Schnauzers were the slowest in this test. For testing the social learning ability of dogs we formed three breed groups (“utility”, “shepherd” and “hunting”). There were no significant differences between these, all the breed groups learned equally well from the human demonstrator. However, we found that dogs belonging to the “shepherd” group looked back more frequently to their owner than the dogs in the “hunting” group. Further, we have found that the age of pet dogs did not affect their social learning ability in the detour task. Our results showed that the pet status of a dog has probably a stronger effect on its cognitive performance and human related behaviour than its age or breed. These results emphasize that socialization and common activities with the dog might overcome the possible breed differences, if we give the dogs common problem solving, or social learning tasks. |
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0168-1591 |
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Equine Behaviour @ team @ |
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6584 |
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Hodgson, D.; Howe, S.; Jeffcott, L.; Reid, S.; Mellor, D.; Higgins, A. |
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Effect of prolonged use of altrenogest on behaviour in mares |
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Year |
2005 |
Publication |
Veterinary journal (London, England : 1997) |
Abbreviated Journal |
Vet J |
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169 |
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1 |
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113-115 |
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Administration, Oral; Anabolic Agents/adverse effects/*pharmacology; Animals; Behavior, Animal/*drug effects; Body Constitution/drug effects; Body Weight/drug effects; *Doping in Sports; Female; Horses/*physiology; Social Behavior; Social Dominance; Time Factors; Trenbolone/adverse effects/*analogs & derivatives/*pharmacology |
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Erratum in:
Vet J. 2005 May;169(3):321.
Corrected and republished in:
Vet J. 2005 May;169(3):322-5.
Oral administration of altrenogest for oestrus suppression in competition horses is believed to be widespread in some equestrian disciplines, and can be administered continuously for several months during a competition season. To examine whether altrenogest has any anabolic or other potential performance enhancing properties that may give a horse an unfair advantage, we examined the effect of oral altrenogest (0.044 mg/kg), given daily for a period of eight weeks, on social hierarchy, activity budget, body-mass and body condition score of 12 sedentary mares. We concluded that prolonged oral administration of altrenogest at recommended dose rates to sedentary mares resulted in no effect on dominance hierarchies, body mass or condition score. |
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Faculty of Veterinary Science, University of Sydney, Private Mailbag 4, Narellan Delivery Centre, Narellan, NSW 2567, Australia. davidh@camden.usyd.edu.au |
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1090-0233 |
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PMID:15683772 |
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refbase @ user @ |
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671 |
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Wells, P.G.; Bhuller, Y.; Chen, C.S.; Jeng, W.; Kasapinovic, S.; Kennedy, J.C.; Kim, P.M.; Laposa, R.R.; McCallum, G.P.; Nicol, C.J.; Parman, T.; Wiley, M.J.; Wong, A.W. |
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Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species |
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Journal Article |
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2005 |
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Toxicology and applied pharmacology |
Abbreviated Journal |
Toxicol Appl Pharmacol |
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207 |
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2 Suppl |
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354-366 |
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Developmental pathologies may result from endogenous or xenobiotic-enhanced formation of reactive oxygen species (ROS), which oxidatively damage cellular macromolecules and/or alter signal transduction. This minireview focuses upon several model drugs (phenytoin, thalidomide, methamphetamine), environmental chemicals (benzo[a]pyrene) and gamma irradiation to examine this hypothesis in vivo and in embryo culture using mouse, rat and rabbit models. Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics to free radical intermediates that initiate ROS formation, resulting in oxidation of proteins, lipids and DNA. Oxidative DNA damage and embryopathies are reduced in PHS knockout mice, and in mice treated with PHS inhibitors, antioxidative enzymes, antioxidants and free radical trapping agents. Thalidomide causes embryonic DNA oxidation in susceptible (rabbit) but not resistant (mouse) species. Embryopathies are increased in mutant mice deficient in the antioxidative enzyme glucose-6-phosphate dehydrogenase (G6PD), or by glutathione (GSH) depletion, or inhibition of GSH peroxidase or GSH reductase. Inducible nitric oxide synthase knockout mice are partially protected. Inhibition of Ras or NF-kB pathways reduces embryopathies, implicating ROS-mediated signal transduction. Atm and p53 knockout mice deficient in DNA damage response/repair are more susceptible to xenobiotic or radiation embryopathies, suggesting a teratological role for DNA damage, consistent with enhanced susceptibility to methamphetamine in ogg1 knockout mice with deficient repair of oxidative DNA damage. Even endogenous embryonic oxidative stress carries a risk, since untreated G6PD- or ATM-deficient mice have increased embryopathies. Thus, embryonic processes regulating the balance of ROS formation, oxidative DNA damage and repair, and ROS-mediated signal transduction may be important determinants of teratological risk. |
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Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada |
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0041-008X |
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PMID:16081118 |
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no |
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refbase @ user @ |
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68 |
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Nicol, C.J.; Adachi, M.; Akiyama, T.E.; Gonzalez, F.J. |
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PPARgamma in endothelial cells influences high fat diet-induced hypertension |
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Journal Article |
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Year |
2005 |
Publication |
American journal of hypertension : journal of the American Society of Hypertension |
Abbreviated Journal |
Am J Hypertens |
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Volume |
18 |
Issue |
4 Pt 1 |
Pages |
549-556 |
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Administration, Oral; Animals; Antihypertensive Agents/pharmacology; Blood Pressure/drug effects; Diabetes Mellitus, Type 2/physiopathology; Dietary Fats/*administration & dosage/pharmacology; Dose-Response Relationship, Drug; Endothelial Cells/*metabolism; Female; Heart Rate/drug effects; Hypertension/*etiology; Ligands; Male; Mice; Mice, Knockout; PPAR gamma/*metabolism; Sodium Chloride/administration & dosage/pharmacology; Thiazolidinediones/pharmacology |
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BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands improve human hypertension. However, the mechanism and site of this effect remains unknown, confounded by PPARgamma expression in many cell types, including endothelial cells (ECs). METHODS: To evaluate the vascular role of PPARgamma we used a conditional null mouse model. Specific disruption of PPARgamma in ECs was created by crossing Tie2-Cre+ transgenic (T2T+) and PPARgamma-floxed (fl/fl) mice to generate PPARgamma (fl/fl)T2T+ (PPARgamma E-null) mice. Conscious 8- to 12-week-old congenic PPARgamma (fl/fl)Cre- (wild type) and PPARgamma E-null mice were examined for changes in systolic blood pressure (BP) and heart rate (HR), untreated, after 2 months of salt-loading (drinking water), and after treatment for 3 months with high fat (HF) diet alone or supplemented during the last 2 weeks with rosiglitazone (3 mg/kg/d). RESULTS: Untreated PPARgamma E-nulls were phenotypically indistinguishable from wild-type littermates. However, compared to similarly treated wild types, HF-treated PPARgamma E-nulls had significantly elevated systolic BP not seen after normal diet or salt-loading. Despite sex-dependent baseline differences, salt-loaded and HF-treated PPARgamma E-nulls of either sex had significantly elevated HR versus wild types. Interestingly, rosiglitazone improved serum insulin levels, but not HF diet-induced hypertension, in PPARgamma E-null mice. CONCLUSIONS: These results suggest that PPARgamma in ECs not only is an important regulator of hypertension and HR under stressed conditions mimicking those arising in type 2 diabetics, but also mediates the antihypertensive effects of rosiglitazone. These data add evidence supporting a beneficial role for PPARgamma-specific ligands in the treatment of hypertension, and suggest therapeutic strategies targeting ECs may prove useful. |
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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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0895-7061 |
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PMID:15831367 |
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refbase @ user @ |
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69 |
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Crosby, M.B.; Svenson, J.L.; Zhang, J.; Nicol, C.J.; Gonzalez, F.J.; Gilkeson, G.S. |
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Title |
Peroxisome proliferation-activated receptor (PPAR)gamma is not necessary for synthetic PPARgamma agonist inhibition of inducible nitric-oxide synthase and nitric oxide |
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Journal Article |
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Year |
2005 |
Publication |
The Journal of pharmacology and experimental therapeutics |
Abbreviated Journal |
J Pharmacol Exp Ther |
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Volume |
312 |
Issue |
1 |
Pages |
69-76 |
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Animals; Cell Line; Gene Expression/drug effects; Macrophages/drug effects/metabolism; Mice; Mice, Inbred C57BL; Nitric Oxide/*metabolism; Nitric Oxide Synthase/*metabolism; Nitric Oxide Synthase Type II; PPAR delta/metabolism; PPAR gamma/*agonists/deficiency; Thiazolidinediones/pharmacology |
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Peroxisome proliferation-activated receptor (PPAR)gamma agonists inhibit inducible nitric-oxide synthase (iNOS), tumor necrosis factor-alpha, and interleukin-6. Because of these effects, synthetic PPARgamma agonists, including thiazolidinediones, are being studied for their impact on inflammatory disease. The anti-inflammatory concentrations of synthetic PPARgamma agonists range from 10 to 50 microM, whereas their binding affinity for PPARgamma is in the nanomolar range. The specificity of synthetic PPARgamma agonists for PPARgamma at the concentrations necessary for anti-inflammatory effects is thus in question. We report that PPARgamma is not necessary for the inhibition of iNOS by synthetic PPARgamma agonists. RAW 264.7 macrophages possess little PPARgamma, yet lipopolysaccharide (LPS)/interferon (IFN)gamma-induced iNOS was inhibited by synthetic PPARgamma agonists at 20 microM. Endogenous PPARgamma was inhibited by the transfection of a dominant-negative PPARgamma construct into murine mesangial cells. In the transfected cells, synthetic PPARgamma agonists inhibited iNOS production at 10 microM, similar to nontransfected cells. Using cells from PPARgamma Cre/lox conditional knockout mice, baseline and LPS/IFNgamma-induced nitric oxide levels were higher in macrophages lacking PPARgamma versus controls. However, synthetic PPARgamma agonists inhibited iNOS at 10 microM in the PPARgamma-deficient cells, similar to macrophages from wild-type mice. These results indicate that PPARgamma is not necessary for inhibition of iNOS expression by synthetic PPARgamma agonists at concentrations over 10 microM. Intrinsic PPARgamma function, in the absence of synthetic agonists, however, may play a role in inflammatory modulation. |
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Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA |
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0022-3565 |
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PMID:15356214 |
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refbase @ user @ |
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73 |
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Lyda, R.O.; Hall, J.R.; Kirkpatrick, J.F. |
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A comparison of Freund's Complete and Freund's Modified Adjuvants used with a contraceptive vaccine in wild horses (Equus caballus) |
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Journal Article |
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Year |
2005 |
Publication |
Journal of zoo and wildlife medicine : official publication of the American Association of Zoo Veterinarians |
Abbreviated Journal |
J Zoo Wildl Med |
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Volume |
36 |
Issue |
4 |
Pages |
610-616 |
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Animals; Antibody Formation; Contraception, Immunologic/*veterinary; Estrus/drug effects; Female; Freund's Adjuvant/administration & dosage/adverse effects/*immunology; Horses/immunology/*physiology; *Vaccines, Contraceptive; Zona Pellucida/*immunology |
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Fifteen captive wild mares (Equus caballus) were treated with porcine zona pellucida contraceptive vaccine and either Freund's Complete Adjuvant (n = 7) or Freund's Modified Adjuvant (n = 8). All mares received a booster inoculation of porcine zona pellucida plus Freund's Incomplete Adjuvant a month later. Anti-porcine zona pellucida antibodies were measured over 10 mo following the initial inoculation. There were no significant differences in antibody titers at any point during the 10 mo, and seven of the eight mares in the Freund's Modified Adjuvant group were above the 60% level at the end of the study, which is considered to be the contraceptive threshold for horses. There were no significant differences in titers between pregnant and nonpregnant horses, nor was there a significant correlation between age and titers. One local injection site reaction occurred after booster treatment with Freund's Incomplete Adjuvant, and 11 healthy foals were born during the course of the study. These data suggest that Freund's Modified Adjuvant is an acceptable substitute for Freund's Complete Adjuvant in certain free-ranging and captive wildlife species. |
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Science and Conservation Center, 2100 South Shiloh Road, Billings, Montana 59106, USA |
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1042-7260 |
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PMID:17312717 |
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no |
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refbase @ user @ |
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139 |
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Author |
de Waal, F.B.M. |
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Title |
A century of getting to know the chimpanzee |
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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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Living Links, Yerkes National Primate Research Center, Emory University, 954 North Gatewood Road, Atlanta, Georgia 30322, USA. dewaal@emory.edu |
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1476-4687 |
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PMID:16136128 |
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no |
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Call Number |
refbase @ user @ |
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162 |
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Author |
Whiten, A.; Horner, V.; de Waal, F.B.M. |
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Title |
Conformity to cultural norms of tool use in chimpanzees |
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Journal Article |
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Year |
2005 |
Publication |
Nature |
Abbreviated Journal |
Nature |
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Volume |
437 |
Issue |
7059 |
Pages |
737-740 |
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Keywords |
Aging/physiology; Animals; Culture; Feeding Behavior/physiology; Female; Pan troglodytes/*physiology/*psychology; *Social Conformity; Technology; Time Factors |
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Abstract |
Rich circumstantial evidence suggests that the extensive behavioural diversity recorded in wild great apes reflects a complexity of cultural variation unmatched by species other than our own. However, the capacity for cultural transmission assumed by this interpretation has remained difficult to test rigorously in the field, where the scope for controlled experimentation is limited. Here we show that experimentally introduced technologies will spread within different ape communities. Unobserved by group mates, we first trained a high-ranking female from each of two groups of captive chimpanzees to adopt one of two different tool-use techniques for obtaining food from the same 'Pan-pipe' apparatus, then re-introduced each female to her respective group. All but two of 32 chimpanzees mastered the new technique under the influence of their local expert, whereas none did so in a third population lacking an expert. Most chimpanzees adopted the method seeded in their group, and these traditions continued to diverge over time. A subset of chimpanzees that discovered the alternative method nevertheless went on to match the predominant approach of their companions, showing a conformity bias that is regarded as a hallmark of human culture. |
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Centre for Social Learning and Cognitive Evolution, School of Psychology, University of St Andrews, St Andrews, Fife, KY16 9JP, UK. a.whiten@st-and.ac.uk |
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English |
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1476-4687 |
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PMID:16113685 |
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refbase @ user @ |
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163 |
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