1,620 research outputs found

    Frustrations of fur-farmed mink

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    Captive animals may suffer if strongly motivated to perform activities that their housing does not allow. We investigated this experimentally for caged mink, and found that they would pay high costs to perform a range of natural behaviours, and release cortisol if their most preferred activity, swimming, was prevented. Investigates the effect of limitations on caged mink. Popularity of fur farming; Research into the possible deprivation of mink, which result in their frustration; Details of the experiment; Impact of an access to water; Results which indicate that fur-farmed mink are still motivated to perform the same activities as their wild counterpart

    Impact of protein-ligand solvation and desolvation on transition state thermodynamic properties of adenosine A2Aligand binding kinetics

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    Ligand-protein binding kinetic rates are growing in importance as parameters to consider in drug discovery and lead optimization. In this study we analysed using surface plasmon resonance (SPR) the transition state (TS) properties of a set of six adenosine A2Areceptor inhibitors, belonging to both the xanthine and the triazolo-triazine scaffolds. SPR highlighted interesting differences among the ligands in the enthalpic and entropic components of the TS energy barriers for the binding and unbinding events. To better understand at a molecular level these differences, we developed suMetaD, a novel molecular dynamics (MD)-based approach combining supervised MD and metadynamics. This method allows simulation of the ligand unbinding and binding events. It also provides the system conformation corresponding to the highest energy barrier the ligand is required to overcome to reach the final state. For the six ligands evaluated in this study their TS thermodynamic properties were linked in particular to the role of water molecules in solvating/desolvating the pocket and the small molecules. suMetaD identified kinetic bottleneck conformations near the bound state position or in the vestibule area. In the first case the barrier is mainly enthalpic, requiring the breaking of strong interactions with the protein. In the vestibule TS location the kinetic bottleneck is instead mainly of entropic nature, linked to the solvent behaviour

    The role of a disulfide bridge in the stability and folding kinetics of Arabidopsis thaliana cytochrome c6A

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    Cytochrome c 6A is a eukaryotic member of the Class I cytochrome c family possessing a high structural homology with photosynthetic cytochrome c 6 from cyanobacteria, but structurally and functionally distinct through the presence of a disulfide bond and a heme mid-point redox potential of + 71 mV (vs normal hydrogen electrode). The disulfide bond is part of a loop insertion peptide that forms a cap-like structure on top of the core α-helical fold. We have investigated the contribution of the disulfide bond to thermodynamic stability and (un)folding kinetics in cytochrome c 6A from Arabidopsis thaliana by making comparison with a photosynthetic cytochrome c 6 from Phormidium laminosum and through a mutant in which the Cys residues have been replaced with Ser residues (C67/73S). We find that the disulfide bond makes a significant contribution to overall stability in both the ferric and ferrous heme states. Both cytochromes c 6A and c 6 fold rapidly at neutral pH through an on-pathway intermediate. The unfolding rate for the C67/73S variant is significantly increased indicating that the formation of this region occurs late in the folding pathway. We conclude that the disulfide bridge in cytochrome c 6A acts as a conformational restraint in both the folding intermediate and native state of the protein and that it likely serves a structural rather than a previously proposed catalytic role. © 2011 Elsevier B.V. All rights reserved

    Recruitment of ethnic minority patients to a cardiac rehabilitation trial: The Birmingham Rehabilitation Uptake Maximisation (BRUM) study [ISRCTN72884263]

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    Background: Concerns have been raised about low participation rates of people from minority ethnic groups in clinical trials. However, the evidence is unclear as many studies do not report the ethnicity of participants and there is insufficient information about the reasons for ineligibility by ethnic group. Where there are data, there remains the key question as to whether ethnic minorities more likely to be ineligible (e.g. due to language) or decline to participate. We have addressed these questions in relation to the Birmingham Rehabilitation Uptake Maximisation (BRUM) study, a randomized controlled trial (RCT) comparing a home-based with a hospital-based cardiac rehabilitation programme in a multi-ethnic population in the UK. Methods: Analysis of the ethnicity, age and sex of presenting and recruited subjects for a trial of cardiac rehabilitation in the West-Midlands, UK. Participants: 1997 patients presenting post-myocardial infarction, percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Data collected: exclusion rates, reasons for exclusion and reasons for declining to participate in the trial by ethnic group. Results: Significantly more patients of South Asian ethnicity were excluded (52% of 'South Asian' v 36% 'White European' and 36% 'Other', p < 0.001). This difference in eligibility was primarily due to exclusion on the basis of language (i.e. the inability to speak English or Punjabi). Of those eligible, similar proportions were recruited from the different ethnic groups (white, South Asian and other). There was a marked difference in eligibility between people of Indian, Pakistani or Bangladeshi origin

    Hunt for Planet Nine: Atmosphere, Spectra, Evolution, and Detectability

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    We investigate the physical characteristics of the solar system\u27s proposed Planet Nine using modeling tools with a heritage of studying Uranus and Neptune. For a range of plausible masses and interior structures, we find upper limits on the intrinsic , from ~35 to 50 K for masses of 5–20 M ⊕, and we also explore lower values. Possible planetary radii could readily span from 2.7 to 6 R ⊕, depending on the mass fraction of any H/He envelope. Given its cold atmospheric temperatures, the planet encounters significant methane condensation, which dramatically alters the atmosphere away from simple Neptune-like expectations. We find that the atmosphere is strongly depleted in molecular absorption at visible wavelengths, suggesting a Rayleigh scattering atmosphere with a high geometric albedo approaching 0.75. We highlight two diagnostics for the atmosphere\u27s temperature structure: (1) the value of the methane mixing ratio above the methane cloud and (2) the wavelength at which cloud scattering can be seen, which yields the cloud-top pressure. Surface reflection may be seen if the atmosphere is thin. Due to collision-induced opacity of H2 in the infrared, the planet would be extremely blue instead of red in the shortest wavelength WISE colors if methane is depleted and would, in some cases, exist on the verge of detectability by WISE. For a range of models, thermal fluxes from ~3 to 5 μm are ~20 orders of magnitude larger than blackbody expectations. We report a search of the AllWISE Source Catalog for Planet Nine, but find no detection

    A One Health Framework for the Evaluation of Rabies Control Programmes: A Case Study from Colombo City, Sri Lanka

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    <div><p>Background</p><p>One Health addresses complex challenges to promote the health of all species and the environment by integrating relevant sciences at systems level. Its application to zoonotic diseases is recommended, but few coherent frameworks exist that combine approaches from multiple disciplines. Rabies requires an interdisciplinary approach for effective and efficient management.</p><p>Methodology/Principal Findings</p><p>A framework is proposed to assess the value of rabies interventions holistically. The economic assessment compares additional monetary and non-monetary costs and benefits of an intervention taking into account epidemiological, animal welfare, societal impact and cost data. It is complemented by an ethical assessment. The framework is applied to Colombo City, Sri Lanka, where modified dog rabies intervention measures were implemented in 2007. The two options included for analysis were the control measures in place until 2006 (“baseline scenario”) and the new comprehensive intervention measures (“intervention”) for a four-year duration. Differences in control cost; monetary human health costs after exposure; Disability-Adjusted Life Years (DALYs) lost due to human rabies deaths and the psychological burden following a bite; negative impact on animal welfare; epidemiological indicators; social acceptance of dogs; and ethical considerations were estimated using a mixed method approach including primary and secondary data. Over the four years analysed, the intervention cost US $1.03 million more than the baseline scenario in 2011 prices (adjusted for inflation) and caused a reduction in dog rabies cases; 738 DALYs averted; an increase in acceptability among non-dog owners; a perception of positive changes in society including a decrease in the number of roaming dogs; and a net reduction in the impact on animal welfare from intermediate-high to low-intermediate.</p><p>Conclusions</p><p>The findings illustrate the multiple outcomes relevant to stakeholders and allow greater understanding of the value of the implemented rabies control measures, thereby providing a solid foundation for informed decision-making and sustainable control.</p></div

    Cognitive Information Processing

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    Contains research objectives.National Institutes of Health (Grant 5 POI GM14940-06)National Institutes of Health (Grant 1 P01 GM19428-01)National Science Foundation (Grant GK-33736X)Joint Services Electronics Programs (U. S. Army, U. S. Navy, and U. S. Air Force) under Contract DAAB07-71-C-0300Grant from the Associated PressPeter Bent Brigham Hospital Purchase Orders F64088Peter Bent Brigham Hospital Purchase Orders F6580

    CMB observations from the CBI and VSA: A comparison of coincident maps and parameter estimation methods

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    We present coincident observations of the Cosmic Microwave Background (CMB) from the Very Small Array (VSA) and Cosmic Background Imager (CBI) telescopes. The consistency of the full datasets is tested in the map plane and the Fourier plane, prior to the usual compression of CMB data into flat bandpowers. Of the three mosaics observed by each group, two are found to be in excellent agreement. In the third mosaic, there is a 2 sigma discrepancy between the correlation of the data and the level expected from Monte Carlo simulations. This is shown to be consistent with increased phase calibration errors on VSA data during summer observations. We also consider the parameter estimation method of each group. The key difference is the use of the variance window function in place of the bandpower window function, an approximation used by the VSA group. A re-evaluation of the VSA parameter estimates, using bandpower windows, shows that the two methods yield consistent results.Comment: 10 pages, 6 figures. Final version. Accepted for publication in MNRA
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