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Pierce, M. M., & Nall, B. T. (2000). Coupled kinetic traps in cytochrome c folding: His-heme misligation and proline isomerization. J Mol Biol, 298(5), 955–969.
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.
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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Kirkpatrick, J. F., Liu, I. M., Turner, J. W. J., Naugle, R., & Keiper, R. (1992). Long-term effects of porcine zonae pellucidae immunocontraception on ovarian function in feral horses (Equus caballus). J Reprod Fertil, 94(2), 437–444.
Abstract: Ten feral mares free-roaming in Maryland, USA, were inoculated with porcine zonae pellucidae (PZP) protein before the breeding season for three consecutive years (1988-90). Ovarian function was monitored for 51 days during the peak of the breeding season after the third annual PZP inoculation, in seven of these mares and in four untreated control mares, by means of urinary oestrone conjugates and nonspecific progesterone metabolites. None of the ten inoculated mares became pregnant in 1990, compared with 55% of 20 control mares, which included two of the four monitored for ovarian function. Three of the untreated mares demonstrated apparent normal ovarian activity, characterized by preovulatory oestrogen peaks, concurrent progesterone nadirs at ovulation, breeding activity, and luteal-phase progesterone increases after ovulation. Two of the seven monitored PZP-treated mares demonstrated ovulatory cycles that did not result in conception. One was pregnant as a result of conception in 1989 and demonstrated a normal, late-gestation, endocrine profile. The remaining four PZP-treated mares revealed no evidence of ovulation, and urinary oestrogen concentrations were significantly depressed. The experiments indicated that (i) a third consecutive annual PZP booster inoculation is greater than 90% effective in preventing pregnancies in mares and (ii) three consecutive years of PZP treatment may interfere with normal ovarian function as shown by markedly depressed oestrogen secretion.
Keywords: Animals; Contraception, Immunologic/*veterinary; *Egg Proteins; Estrogens, Conjugated (USP)/urine; Female; Glycoproteins/*pharmacology; Horses/immunology/*physiology; *Membrane Glycoproteins; Ovary/drug effects/*physiology; Progesterone/metabolism; *Receptors, Cell Surface; Swine/immunology; Time Factors; Zona Pellucida/*immunology
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Turner, J. W. J., & Kirkpatrick, J. F. (1982). Androgens, behaviour and fertility control in feral stallions. J Reprod Fertil Suppl, 32, 79–87.
Abstract: This field study of feral stallions in Montana and Idaho examines and correlates the seasonal pattern of plasma androgens and specific sociosexual behaviour and reports the effect of a long-acting androgenic steroid on this behaviour and on fertility. Plasma testosterone was measured by competitive protein binding assay in samples obtained by jugular venepuncture from captured animals. In samples taken from 34 sexually mature stallions in 6 different months during the year, a definite seasonal pattern in testosterone was present, with a peak in May (3.04 +/- 0.63 ng/ml) and a nadir in December (1.55 +/- 0.34 ng/ml). Values were less than 2.0 ng/ml in non-breeding months and greater than 2.4 ng/ml in breeding months. Behavioural endpoints measured were (1) stallion scent marking in response to elimination by mares (elimination marking), (2) mounting and (3) copulation. The frequencies of each of these endpoints followed closely the seasonal pattern seen for plasma androgens. In the fertility study microcapsulated testosterone propionate (microTP) was administered i.m. to 10 harem stud stallions 3 months before the 1980 breeding season. In these stallions and in 10 control harem studs, the above behavioural endpoints were examined in the 1980 and 1981 breeding seasons, and foal counts were made in 1981. There were no direct inhibitory or stimulatory effects of microTP treatment on any of the behavioural endpoints in either year. In 1981 foals were produced in 87.5% of the control bands and 28.4% of the microTP-treated bands. These results indicate that microencapsulated testosterone propionate can provide effective fertility control in feral horses without causing significant alterations in sociosexual behaviour.
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Loyola, E. G., Rodriguez, M. H., Gonzalez, L., Arredondo, J. I., Bown, D. N., & Vaca, M. A. (1990). Effect of indoor residual spraying of DDT and bendiocarb on the feeding patterns of Anopheles pseudopunctipennis in Mexico. J Am Mosq Control Assoc, 6(4), 635–640.
Abstract: Intense and persistent use of DDT for malaria control has increased resistance and induced exophilic behavior of Anopheles pseudopunctipennis. An evaluation of bendiocarb and DDT to control this species in Sinaloa, Mexico, showed that, in spite of DDT-resistance, both insecticides produced similar effects. Feeding patterns were analyzed to explain these results. Resting mosquitoes were collected over the dry and wet seasons. Anophelines were tested in an ELISA to determine the source of the meals. The human blood index (HBI) ranged from 3.3 to 6.8% in DDT- and from 12.7 to 26.9% in bendiocarb-sprayed houses. Irritability and repellency in DDT-sprayed houses could explain the reduced HBI. In contrast, bendiocarb produced higher mortality. These effects could have affected different components of the vectorial capacity and similarly reduced malaria.
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Madigan, J. E., & Bell, S. A. (2001). Owner survey of headshaking in horses. J Am Vet Med Assoc, 219(3), 334–337.
Abstract: OBJECTIVE: To determine signalment, history, clinical signs, duration, seasonality, and response to various treatments reported by owners for headshaking in horses. DESIGN: Owner survey. ANIMALS: 109 horses with headshaking. PROCEDURE: Owners of affected horses completed a survey questionnaire. RESULTS: 78 affected horses were geldings, 29 were mares, and 2 were stallions. Mean age of onset was 9 years. Headshaking in 64 horses had a seasonal component, and for most horses, headshaking began in spring and ceased in late summer or fall. The most common clinical signs were shaking the head in a vertical plane, acting like an insect was flying up the nostril, snorting excessively, rubbing the muzzle on objects, having an anxious expression while headshaking, worsening of clinical signs with exposure to sunlight, and improvement of clinical signs at night. Treatment with antihistamines, nonsteroidal anti-inflammatory drugs, corticosteroids, antimicrobials, fly control, chiropractic, and acupuncture had limited success. Sixty-one horses had been treated with cyproheptadine; 43 had moderate to substantial improvement. CONCLUSIONS AND CLINICAL RELEVANCE: Headshaking may have many causes. A large subset of horses have similar clinical signs including shaking the head in a vertical plane, acting as if an insect were flying up the nostrils, and rubbing the muzzle on objects. Seasonality and worsening of clinical signs with exposure to light are also common features of this syndrome. Geldings and Thoroughbreds appear to be overrepresented. Cyproheptadine treatment was beneficial in more than two thirds of treated horses.
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Aronson, L. (1998). Animal behavior case of the month. Aggression directed toward other horses. J Am Vet Med Assoc, 213(3), 358–359.
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Grubb, T. L., Foreman, J. H., Benson, G. J., Thurmon, J. C., Tranquilli, W. J., Constable, P. D., et al. (1996). Hemodynamic effects of calcium gluconate administered to conscious horses. J Vet Intern Med, 10(6), 401–404.
Abstract: Calcium gluconate was administered to conscious horses at 3 different rates (0.1, 0.2, and 0.4 mg/kg/min for 15 minutes each). Serum calcium concentrations and parameters of cardiovascular function were evaluated. All 3 calcium administration rates caused marked increases in both ionized and total calcium concentrations, cardiac index, stroke index, and cardiac contractility (dP/dtmax). Mean arterial pressure and right atrial pressure were unchanged; heart rate decreased markedly during calcium administration. Ionized calcium concentration remained between 54% and 57% of total calcium concentration throughout the study. We conclude that calcium gluconate can safely be administered to conscious horses at 0.1 to 0.4 mg/kg/min and that administration will result in improved cardiac function.
Keywords: Animals; Blood Pressure/drug effects/physiology; Calcium/blood; Calcium Gluconate/administration & dosage/*pharmacology; Cardiac Output/drug effects/physiology; Consciousness/*physiology; Dose-Response Relationship, Drug; Female; Heart Rate/drug effects/physiology; Hemodynamic Processes/*drug effects/physiology; Horses/blood/*physiology; Infusions, Intravenous; Male; Myocardial Contraction/drug effects/physiology; Respiration/drug effects/physiology; Stroke Volume/drug effects/physiology; Time Factors
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Rietmann, T. R., Stauffacher, M., Bernasconi, P., Auer, J. A., & Weishaupt, M. A. (2004). The association between heart rate, heart rate variability, endocrine and behavioural pain measures in horses suffering from laminitis. J Vet Med A Physiol Pathol Clin Med, 51(5), 218–225.
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.
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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Tobin, T., & Combie, J. D. (1982). Performance testing in horses: a review of the role of simple behavioral models in the design of performance experiments. J Vet Pharmacol Ther, 5(2), 105–118.
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Lyda, R. O., Hall, J. R., & Kirkpatrick, J. F. (2005). A comparison of Freund's Complete and Freund's Modified Adjuvants used with a contraceptive vaccine in wild horses (Equus caballus). J Zoo Wildl Med, 36(4), 610–616.
Abstract: 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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