Inhibition of neutral cholesteryl ester hydrolase by a naturally occurring cytosolic protein in macrophages

AbstractThe soluble fraction from a number of macrophage cell lines has been shown to contain a protein(s) that inhibits neutral cholesteryl ester hydrolase. The inhibition is dependent on the concentration of soluble protein used, and the efficiency of the inhibitor can be influenced by the inclusion of oleate and an inhibitor of ACAT. It is suggested that the presence of this material indicates that the macrophage contains a means of negatively controlling the activity of the hydrolytic phase of the cholesterol/cholesteryl ester cycle

Cumulative mutagenesis of the basic residues in the 201-218 region of insulin-like growth factor (IGF)-binding protein-5 results in progressive loss of both IGF-I binding and inhibition of IGF-I biological action

We have reported previously that mutation of two conserved nonbasic amino acids (G203 and Q209) within the highly basic 201–218 region in the C-terminal domain of IGF-binding protein-5 (IGFBP-5) decreases binding to IGFs. This study reveals that cumulative mutagenesis of the 10 basic residues in this region, to create the C-Term series of mutants, ultimately results in a 15-fold decrease in the affinity for IGF-I and a major loss in heparin binding. We examined the ability of mutants to inhibit IGF-mediated survival of MCF-7 cells and were able to demonstrate that this depended not only upon the affinity for IGF-I, but also the kinetics of this interaction, because IGFBP-5 mutants with similar affinity constants (KD) values, but with different association (Ka) and dissociation (Kd) rate values, had markedly different inhibitory properties. In contrast, the affinity for IGF-I provided no predictive value in terms of the ability of these mutants to enhance IGF action when bound to the substratum. Instead, these C-Term mutants appeared to enhance the actions of IGF-I by a combination of increased dissociation of IGF-IGFBP complexes from the substratum, together with dissociation of IGF-I from IGFBP-5 bound to the substratum. These effects of the IGFBPs were dependent upon binding to IGF-I, because a non-IGF binding mutant (N-Term) was unable to inhibit or enhance the actions of IGF-I. These results emphasize the importance of the kinetics of association/dissociation in determining the enhancing or inhibiting effects of IGFBP-5 and demonstrate the ability to generate an IGFBP-5 mutant with exclusively IGF-enhancing activity

Core excitations across the neutron shell gap in ²⁰⁷Tl

The single closed-neutron-shell, one proton-hole nucleus 207Tl was populated in deep-inelastic collisions of a 208Pb beam with a 208Pb target. The yrast and near-yrast level scheme has been established up to high excitation energy, comprising an octupol

Octupole transitions in the 208Pb region

The 208Pb region is characterised by the existence of collective octupole states. Here we populated such states in 208Pb + 208Pb deep-inelastic reactions. γ-ray angular distribution measurements were used to infer the octupole character of several E3 transitions. The octupole character of the 2318 keV 17− → 14+ in 208Pb, 2485 keV 19/2 − → 13/2 + in 207Pb, 2419 keV 15/2 − → 9/2 + in 209Pb and 2465 keV 17/2 + → 11/2 − in 207Tl transitions was demonstrated for the first time. In addition, shell model calculations were performed using two different sets of two-body matrix elements. Their predictions were compared with emphasis on collective octupole states.This work is supported by the Science and Technology Facilities Council (STFC), UK, US Department of Energy, Office of Nuclear Physics, under Contract No. DEAC02-06CH11357 and DE-FG02-94ER40834, NSF grant PHY-1404442

Spin Glass Ordering in Diluted Magnetic Semiconductors: a Monte Carlo Study

We study the temperature-dilution phase diagram of a site-diluted Heisenberg antiferromagnet on a fcc lattice, with and without the Dzyaloshinskii-Moriya anisotropic term, fixed to realistic microscopic parameters for $IIB_{1-x} Mn_x Te$ (IIB=Cd, Hg, Zn). We show that the dipolar Dzyaloshinskii-Moriya anisotropy induces a finite-temperature phase transition to a spin glass phase, at dilutions larger than 80%. The resulting probability distribution of the order parameter P(q) is similar to the one found in the cubic lattice Edwards-Anderson Ising model. The critical exponents undergo large finite size corrections, but tend to values similar to the ones of the Edwards-Anderson-Ising model.Comment: 4 pages plus 3 postscript figure

Rethinking cultural diversity in the UK film sector:practices in community filmmaking

© The Author(s) 2017. Academic, policy and industry debates have tended to focus on the mainstream film sector when discussing cultural diversity. One of the persistent challenges for the sector has been how to diversify cultural representation and participation. This article suggests that participatory modes of community filmmaking make an important contribution to cultural diversity. Drawing on an evidence base derived from qualitative research conducted in three English regions, the article shifts the spotlight away from the mainstream and onto the margins of the film sector in order to explore more ‘bottom-up’ approaches to cultural diversity. It examines how community filmmakers interpret and engage with questions of cultural diversity and how this connects to the participatory and business practices that they adopt. The findings highlight the significance of processes of practice in how mediated cultural diversity manifests itself and the value of community filmmaking in contributing to wider cultural diversity debates and practices.The authors thank the Arts and Humanities Research Council (UK) for funding the ‘Community Filmmaking and Cultural Diversity: Practice, Innovation and Policy project’ (2013–2014)

The Role of Ethics and Targets in Environmental Governance and the Enduring Importance of New Public Management

This article examines the importance of new public management in environmental governance. In order to explain what makes new public management such a robust framework for environmental governance, the article draws on the key themes of individual and collective responsibility in responding to climate change, examining the role of new public management in response to ecological and environmental change, resource scarcity, focus on global energy sources and politics. The article discusses the role of three aspects of environmental governance in turn: the theoretical understandings relating to individuals and society in response to climate change, the politics of these responses and governance arrangements, and how these are formed by the hastening paucity of certain energy resources. The article then moves on to examine these themes in the context of new public management, arguing that the responses we see to climate change in environmental governance are driven by measurement and targets, as these can be universally set and communicated. This shows the enduring nature of new public management in political and policy responses to the challenges of climate change

Standard set of health outcome measures for older persons

Background: The International Consortium for Health Outcomes Measurement (ICHOM) was founded in 2012 to propose consensus-based measurement tools and documentation for different conditions and populations.This article describes how the ICHOM Older Person Working Group followed a consensus-driven modified Delphi technique to develop multiple global outcome measures in older persons. The standard set of outcome measures developed by this group will support the ability of healthcare systems to improve their care pathways and quality of care. An additional benefit will be the opportunity to compare variations in outcomes which encourages and supports learning between different health care systems that drives quality improvement. These outcome measures were not developed for use in research. They are aimed at non researchers in healthcare provision and those who pay for these services. Methods: A modified Delphi technique utilising a value based healthcare framework was applied by an international panel to arrive at consensus decisions.To inform the panel meetings, information was sought from literature reviews, longitudinal ageing surveys and a focus group. Results: The outcome measures developed and recommended were participation in decision making, autonomy and control, mood and emotional health, loneliness and isolation, pain, activities of daily living, frailty, time spent in hospital, overall survival, carer burden, polypharmacy, falls and place of death mapped to a three tier value based healthcare framework. Conclusions: The first global health standard set of outcome measures in older persons has been developed to enable health care systems improve the quality of care provided to older persons

Designing programs for eliminating canine rabies from islands: Bali, Indonesia as a case study

<p>Background: Canine rabies is one of the most important and feared zoonotic diseases in the world. In some regions rabies elimination is being successfully coordinated, whereas in others rabies is endemic and continues to spread to uninfected areas. As epidemics emerge, both accepted and contentious control methods are used, as questions remain over the most effective strategy to eliminate rabies. The Indonesian island of Bali was rabies-free until 2008 when an epidemic in domestic dogs began, resulting in the deaths of over 100 people. Here we analyze data from the epidemic and compare the effectiveness of control methods at eliminating rabies.</p> <p>Methodology/Principal Findings: Using data from Bali, we estimated the basic reproductive number, R0, of rabies in dogs, to be ~1·2, almost identical to that obtained in ten–fold less dense dog populations and suggesting rabies will not be effectively controlled by reducing dog density. We then developed a model to compare options for mass dog vaccination. Comprehensive high coverage was the single most important factor for achieving elimination, with omission of even small areas (<0.5% of the dog population) jeopardizing success. Parameterizing the model with data from the 2010 and 2011 vaccination campaigns, we show that a comprehensive high coverage campaign in 2012 would likely result in elimination, saving ~550 human lives and ~$15 million in prophylaxis costs over the next ten years.</p> <p>Conclusions/Significance: The elimination of rabies from Bali will not be achieved through achievable reductions in dog density. To ensure elimination, concerted high coverage, repeated, mass dog vaccination campaigns are necessary and the cooperation of all regions of the island is critical. Momentum is building towards development of a strategy for the global elimination of canine rabies, and this study offers valuable new insights about the dynamics and control of this disease, with immediate practical relevance.</p&gt

Isomer Spectroscopy of Neutron-rich 165,167Tb

Open Access JournalWe present information on the excited states in the prolate-deformed, neutron-rich nuclei 165;167Tb100;102. The nuclei of interest were synthesized following in-flight fission of a 345 MeV per nucleon 238U primary beam on a 2 mm 9Be target at the Radioactive Ion-Beam Factory (RIBF), RIKEN, Japan. The exotic nuclei were separated and identified event-by-event using the BigRIPS separator, with discrete energy gamma-ray decays from isomeric states with half-lives in the _s regime measured using the EURICA gamma-ray spectrometer. Metastable-state decays are identified in 165Tb and 167Tb and interpreted as arising from hindered E1 decay from the 7/2-[523] single quasi-proton Nilsson configuration to rotational states built on the 3/2-[411] single quasi-proton ground state. These data correspond to the first spectroscopic information in the heaviest, odd-A terbium isotopes reported to date and provide information on proton Nilsson configurations which reside close to the Fermi surface as the 170Dy doubly-midshell nucleus is approached.postprin