380 research outputs found

    Time Constants of Heating and Cooling in the Eastern Water Dragon. Physignathus Lesueurii and Some Generalizations About Heating and Cooling in Reptiles

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    In keeping with other reptiles, core temperature of the lizard Physignathus lesueurii responds more rapidly to a step function increase in temperature than to a corresponding decrease. 2. Observations on twelve species (five families) of non-Chelonian reptiles heating and cooling in air and water show that strongly predictable relationships exist between thermal time constants and body size. Chelonia show a different pattern. 3. These observations are compared with the predictions of a simple model which, although not sufficiently complex to simulate physiological changes, provides insight into the relative importance of the physical and biological factors which underlie the observed relationships

    Glucocorticoid receptor Thr524 phosphorylation by MINK1 induces interactions with 14-3-3 protein regulators

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    The glucocorticoid receptor (GR) is a ligand-dependent transcription factor that plays a central role in inflammation. The GR activity is also modulated via protein-protein interactions, including binding of 14-3-3 proteins induced by GR phosphorylation. However, the specific phosphorylation sites on the GR that trigger these interactions and their functional consequences are less clear. Hence, we sought to examine this system in more detail. We used phosphorylated GR peptides, biophysical studies, and X-ray crystallography to identify key residues within the ligand-binding domain of the GR, T524 and S617, whose phosphorylation results in binding of the representative 14-3-3 protein 14-3-3ζ. A kinase screen identified misshapen-like kinase 1 (MINK1) as responsible for phosphorylating T524 and Rho-associated protein kinase 1 for phosphorylating S617; cell-based approaches confirmed the importance of both GR phosphosites and MINK1 but not Rhoassociated protein kinase 1 alone in inducing GR-14-3-3 binding. Together our results provide molecular-level insight into 14-3-3-mediated regulation of the GR and highlight both MINK1 and the GR-14-3-3 axis as potential targets for future therapeutic intervention

    Compilation of basal metabolic and blood perfusion rates in various multi-compartment, whole-body thermoregulation models

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    The assignments of basal metabolic rates (BMR), basal cardiac outputs (BCO) and basal blood perfusion rates (BBPR) were compared in nine multi-compartment, whole body thermoregulation models. The data are presented at three levels of detail: total body, specific body regions and regional body tissue layers. Differences in the assignment of these quantities among the compared models increased with the level of detail, in the above order. The ranges of variability in the total body BMR was 6.5% relative to the lowest value, with a mean of 84.3±2 Watts, and in the BCO it was 8% with a mean of 4.70±0.13 l/min. The least variability among the body regions is seen in the combined torso (shoulders, thorax and abdomen: ±7.8% BMR and ±5.9% BBPR) and in the combined head (head, face, and neck: ±9.9% BMR and ±10.9% BBPR), determined by the ratio of the standard deviation to the mean. Much more variability is apparent in the extremities with the most showing in the BMR of the feet (±117%), followed by the BBPR in the arms (±61.3%). In the tissue layers, most of the bone layers were assigned zero BMR and BBPR, except in the shoulders and in the extremities that were assigned non-zero values in a number of models. The next lowest values were assigned to the fat layers, with occasional zero values. Skin basal values were invariably non-zero but involved very low values in certain models, e.g., BBPR in the feet and the hands. Muscle layers were invariably assigned high values with the highest found in the thorax, abdomen and legs. The brain, lung and viscera layers were assigned the highest of all values of both basal quantities with those of the brain layers showing rather tight ranges of variability in both basal quantities.Average basal values of the "time-seasoned" models presented in this study could be useful as a first step in future modeling efforts, subject to appropriate adjustment of values to conform to most recently available and reliable data

    Control-focused, nonlinear and time-varying modelling of dielectric elastomer actuators with frequency response analysis

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    Current models of dielectric elastomer actuators (DEAs) are mostly constrained to first principal descriptions that are not well suited to the application of control design due to their computational complexity. In this work we describe an integrated framework for the identification of control focused, data driven and time-varying DEA models that allow advanced analysis of nonlinear system dynamics in the frequency-domain. Experimentally generated input–output data (voltage-displacement) was used to identify control-focused, nonlinear and time-varying dynamic models of a set of film-type DEAs. The model description used was the nonlinear autoregressive with exogenous input structure. Frequency response analysis of the DEA dynamics was performed using generalized frequency response functions, providing insight and a comparison into the time-varying dynamics across a set of DEA actuators. The results demonstrated that models identified within the presented framework provide a compact and accurate description of the system dynamics. The frequency response analysis revealed variation in the time-varying dynamic behaviour of DEAs fabricated to the same specifications. These results suggest that the modelling and analysis framework presented here is a potentially useful tool for future work in guiding DEA actuator design and fabrication for application domains such as soft robotics

    The cohesin ring uses its hinge to organize DNA using non-topological as well as topological mechanisms

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    As predicted by the notion that sister chromatid cohesion is mediated by entrapment of sister DNAs inside cohesin rings, there is perfect correlation between co-entrapment of circular minichromosomes and sister chromatid cohesion. In most cells where cohesin loads without conferring cohesion, it does so by entrapment of individual DNAs. However, cohesin with a hinge domain whose positively charged lumen is neutralized loads and moves along chromatin despite failing to entrap DNAs. Thus, cohesin engages chromatin in non-topological, as well as topological, manners. Since hinge mutations, but not Smc-kleisin fusions, abolish entrapment, DNAs may enter cohesin rings through hinge opening. Mutation of three highly conserved lysine residues inside the Smc1 moiety of Smc1/3 hinges abolishes all loading without affecting cohesin’s recruitment to CEN loading sites or its ability to hydrolyze ATP. We suggest that loading and translocation are mediated by conformational changes in cohesin’s hinge driven by cycles of ATP hydrolysis

    Thermoregulatory, metabolic, and cardiovascular responses during 88 min of full-body ice immersion - A case study.

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    Exposure to extreme cold environments is potentially life-threatening. However, the world record holder of full-body ice immersion has repeatedly demonstrated an extraordinary tolerance to extreme cold. We aimed to explore thermoregulatory, metabolic, and cardiovascular responses during 88 min of full-body ice immersion. We continuously measured gastrointestinal temperature (Tgi ), skin temperature (Tskin), blood pressure, and heart rate (HR). Oxygen consumption (VO2 ) was measured at rest, and after 45 and 88 min of ice immersion, in order to calculate the metabolic heat production. Tskin dropped significantly (28-34°C to 4-15°C) and VO2 doubled (5.7-11.3 ml kg-1  min-1 ), whereas Tgi (37.6°C), HR (72 bpm), and mean arterial pressure (106 mmHg) remained stable during the first 30 min of cold exposure. During the remaining of the trial, Tskin and VO2 remained stable, while Tgi gradually declined to 37.0°C and HR and mean arterial blood pressure increased to maximum values of 101 bpm and 115 mmHg, respectively. Metabolic heat production in rest was 169 W and increased to 321 W and 314 W after 45 and 80 min of ice immersion. Eighty-eight minutes of full-body ice immersion resulted in minor changes of Tgi and cardiovascular responses, while Tskin and VO2 changed markedly. These findings may suggest that our participant can optimize his thermoregulatory, metabolic, and cardiovascular responses to challenge extreme cold exposure
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