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Miksovska, J., & Larsen, R. W. (2003). Photothermal studies of pH induced unfolding of apomyoglobin. J Protein Chem, 22(4), 387–394.
Abstract: Conformational dynamic and enthalpy changes associated with pH induced unfolding of apomyoglobin were studied using photoacoustic calorimetry and photothermal beam deflection methods. The transition between the native state and the I intermediate was induced by a nanosecond pH jump from o-nitrobenzaldehyde photolysis. Deconvolution of photoacoustic waves indicates two kinetic processes. The fast phase (T < 50 ns) is characterized by a volume expansion of 8.8 ml mol(-1). This process is followed by a volume contraction of about -22 ml mol(-1) (tau approximately 500 ns). Photothermal beam deflection measurements do not reveal any volume changes on the time scale between approximately 100 micros and 5 ms. We associate the volume contraction with structural changes occurring during the transition between the native state and the I intermediate. The lack of any processes on the ms time scale may indicate the absence of structural events involving larger conformational changes of apomyoglobin after the pH jump.
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Hoang, L., Maity, H., Krishna, M. M. G., Lin, Y., & Englander, S. W. (2003). Folding units govern the cytochrome c alkaline transition. J Mol Biol, 331(1), 37–43.
Abstract: The alkaline transition of cytochrome c is a model for protein structural switching in which the normal heme ligand is replaced by another group. Stopped flow data following a jump to high pH detect two slow kinetic phases, suggesting two rate-limiting structure changes. Results described here indicate that these events are controlled by the same structural unfolding reactions that account for the first two steps in the reversible unfolding pathway of cytochrome c. These and other results show that the cooperative folding-unfolding behavior of protein foldons can account for a variety of functional activities in addition to determining folding pathways.
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Pinchbeck, G. L., Clegg, P. D., Proudman, C. J., Morgan, K. L., & French, N. P. (2003). Case-control study to investigate risk factors for horse falls in hurdle racing in England and Wales. Vet. Rec., 152(19), 583–587.
Abstract: Between March 1, 2000 and August 31, 2001, a case-control study was conducted on 12 racecourses in England and Wales to identify and quantify the risk factors associated with horse falls in hurdle races. The cases and controls were defined so that variables relating to the horse, the jockey, the race and racecourse, and the jump could be considered. The cases were defined as a jumping effort at a hurdle flight that resulted in a fall, and the controls were defined as a successful jump over a hurdle at any of the 12 racecourses within 14 days before or after the case fall. Conditional logistic regression was used to examine the univariable and multivariable relationships between the predictor variables and the risk of falling. The risk of falling was significantly associated with the position of the jump in the race, and with the distance and speed of the race. A horse's previous racing experience and history were also significantly associated with the risk of falling and horses participating in their first hurdle race were at almost five times greater risk of falling than horses that had hurdled before.
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Gulotta, M., Rogatsky, E., Callender, R. H., & Dyer, R. B. (2003). Primary folding dynamics of sperm whale apomyoglobin: core formation. Biophys J, 84(3), 1909–1918.
Abstract: The structure, thermodynamics, and kinetics of heat-induced unfolding of sperm whale apomyoglobin core formation have been studied. The most rudimentary core is formed at pH(*) 3.0 and up to 60 mM NaCl. Steady state for ultraviolet circular dichroism and fluorescence melting studies indicate that the core in this acid-destabilized state consists of a heterogeneous composition of structures of approximately 26 residues, two-thirds of the number involved for horse heart apomyoglobin under these conditions. Fluorescence temperature-jump relaxation studies show that there is only one process involved in Trp burial. This occurs in 20 micro s for a 7 degrees jump to 52 degrees C, which is close to the limits placed by diffusion on folding reactions. However, infrared temperature jump studies monitoring native helix burial are biexponential with times of 5 micro s and 56 micro s for a similar temperature jump. Both fluorescence and infrared fast phases are energetically favorable but the slow infrared absorbance phase is highly temperature-dependent, indicating a substantial enthalpic barrier for this process. The kinetics are best understood by a multiple-pathway kinetics model. The rapid phases likely represent direct burial of one or both of the Trp residues and parts of the G- and H-helices. We attribute the slow phase to burial and subsequent rearrangement of a misformed core or to a collapse having a high energy barrier wherein both Trps are solvent-exposed.
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Golland, L. C., Evans, D. L., McGowan, C. M., Hodgson, D. R., & Rose, R. J. (2003). The effects of overtraining on blood volumes in standardbred racehorses. Vet J, 165(3), 228–233.
Abstract: Red blood cell hypervolaemia has been used for diagnosis of overtraining in racehorses, and has been suggested as a mechanism of this cause of loss of racing performance. The effects of overload training (OLT) on the plasma, blood and red cell volumes were investigated in a prospective study in 12 Standardbred horses. Measurements of blood volumes were made after eight and 32 weeks of an exercise training study. Horses were randomly allocated to OLT and control groups (n=6) after 16 weeks of training. Training duration and intensity were increased more rapidly for the OLT group from week 16, until overtraining was diagnosed in week 32.There were no significant effects of OLT on plasma, blood or total red cell volumes between weeks eight and 32. These volumes significantly decreased with time. Maximal haematocrit after exercise was lower (P<0.05) in the OT group in week 32 (0.57+/-0.003% L/L) than in week eight (0.59+/-0.004 L/L). It was concluded that red cell hypervolaemia was not a mechanism for the decrease in capacity for exercise that occurs with overtraining.
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Ganswindt, A., Palme, R., Heistermann, M., Borragan, S., & Hodges, J. K. (2003). Non-invasive assessment of adrenocortical function in the male African elephant (Loxodonta africana) and its relation to musth. Gen Comp Endocrinol, 134(2), 156–166.
Abstract: Adult male elephants periodically show the phenomenon of musth, a condition associated with increased aggressiveness, restlessness, significant weight reduction and markedly elevated androgen levels. It has been suggested that musth-related behaviours are costly and that therefore musth may represent a form of physiological stress. In order to provide data on this largely unanswered question, the first aim of this study was to evaluate different assays for non-invasive assessment of adrenocortical function in the male African elephant by (i) characterizing the metabolism and excretion of [3H]cortisol (3H-C) and [14C]testosterone (14C-T) and (ii) using this information to evaluate the specificity of four antibodies for determination of excreted cortisol metabolites, particularly with respect to possible cross-reactions with androgen metabolites, and to assess their biological validity using an ACTH challenge test. Based on the methodology established, the second objective was to provide data on fecal cortisol metabolite concentrations in bulls during the musth and non-musth condition. 3H-C (1 mCi) and 14C-T (100 microCi) were injected simultaneously into a 16 year old male and all urine and feces collected for 30 and 86 h, respectively. The majority (82%) of cortisol metabolites was excreted into the urine, whereas testosterone metabolites were mainly (57%) excreted into the feces. Almost all radioactive metabolites recovered from urine were conjugated (86% 3H-C and 97% 14C-T). In contrast, 86% and >99% of the 3H-C and 14C-T metabolites recovered from feces consisted of unconjugated forms. HPLC separations indicated the presence of various metabolites of cortisol in both urine and feces, with cortisol being abundant in hydrolysed urine, but virtually absent in feces. Although all antibodies measured substantial amounts of immunoreactivity after HPLC separation of peak radioactive samples and detected an increase in glucocorticoid output following the ACTH challenge, only two (in feces against 3alpha,11-oxo-cortisol metabolites, measured by an 11-oxo-etiocholanolone-EIA and in urine against cortisol, measured by a cortisol-EIA) did not show substantial cross-reactivity with excreted 14C-T metabolites and could provide an acceptable degree of specificity for reliable assessment of glucocorticoid output from urine and feces. Based on these findings, concentrations of immunoreactive 3alpha,11-oxo-cortisol metabolites were determined in weekly fecal samples collected from four adult bulls over periods of 11-20 months to examine whether musth is associated with increased adrenal activity. Results showed that in each male levels of these cortisol metabolites were not elevated during periods of musth, suggesting that in the African elephant musth is generally not associated with marked elevations in glucocorticoid output. Given the complex nature of musth and the variety of factors that are likely to influence its manifestation, it is clear, however, that further studies, particularly on free-ranging animals, are needed before a possible relationship between musth and adrenal function can be resolved. This study also clearly illustrates the potential problems associated with cross-reacting metabolites of gonadal steroids in EIAs measuring glucocorticoid metabolites. This has to be taken into account when selecting assays and interpreting results of glucocorticoid metabolite analysis, not only for studies in the elephant but also in other species.
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Kalin, N. H., & Shelton, S. E. (2003). Nonhuman primate models to study anxiety, emotion regulation, and psychopathology. Ann N Y Acad Sci, 1008, 189–200.
Abstract: This paper demonstrates that the rhesus monkey provides an excellent model to study mechanisms underlying human anxiety and fear and emotion regulation. In previous studies with rhesus monkeys, stable, brain, endocrine, and behavioral characteristics related to individual differences in anxiety were found. It was suggested that, when extreme, these features characterize an anxious endophenotype and that these findings in the monkey are particularly relevant to understanding adaptive and maladaptive anxiety responses in humans. The monkey model is also relevant to understanding the development of human psychopathology. For example, children with extremely inhibited temperament are at increased risk to develop anxiety disorders, and these children have behavioral and biological alterations that are similar to those described in the monkey anxious endophenotype. It is likely that different aspects of the anxious endophenotype are mediated by the interactions of limbic, brain stem, and cortical regions. To understand the brain mechanisms underlying adaptive anxiety responses and their physiological concomitants, a series of studies in monkeys lesioning components of the neural circuitry (amygdala, central nucleus of the amygdala and orbitofrontal cortex) hypothesized to play a role are currently being performed. Initial findings suggest that the central nucleus of the amygdala modulates the expression of behavioral inhibition, a key feature of the endophenotype. In preliminary FDG positron emission tomography (PET) studies, functional linkages were established between the amygdala and prefrontal cortical regions that are associated with the activation of anxiety.
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Nelson, E. E., Shelton, S. E., & Kalin, N. H. (2003). Individual differences in the responses of naive rhesus monkeys to snakes. Emotion, 3(1), 3–11.
Abstract: The authors demonstrated individual differences in inhibited behavior and withdrawal responses of laboratory-born rhesus monkeys when initially exposed to a snake. Most monkeys displayed a small significant increase in their behavioral inhibition in the presence of a snake. A few monkeys had marked responses, and some actively withdrew. Although the responses of the most extreme laboratory-born monkeys were comparable to feral-born monkeys, the responses of the laboratory-born monkeys rapidly habituated. The individual differences in the responses of naive monkeys likely reflect a continuum from orienting to wariness to fear. A neurobiological model is presented that addresses potential mechanisms underlying these individual differences, their relation to fear, and how they may predispose to phobia development.
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McLean, A. N. (2003).
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Waring, G. H. (2003).
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