Spectroscopic investigations on the interactions of potent platinum(II) anticancer agents with bovine serum albumin

The interactions of three platinum(II)-based anticancer complexes [(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)](2+), [(5,6-dimethyl-1,10-phenanthroline)(1R,2R-diaminocyclohexane)platinum(II)](2+), and [(5,6-dimethyl-1,10-phenanthroline)(1,2-diaminoethane)platinum(II)](2+) (56MEEN) with BSA have been examined by circular dichroism (CD), fluorescence and (1)H pulsed gradient spin–echo (PGSE) diffusion NMR spectroscopy. The number of association constants and sites differed depending upon the spectroscopic method. This may be because each technique monitors different types of interaction/s and/or as a consequence of the different concentration ranges required for each technique. The titration of BSA with the achiral 56MEEN as monitored by CD indicates a reduction in the α-helical nature of the albumin, with the association constant calculated to be ~5 × 10(6) M(−1) for one site. Due to the chiral nature of the other two complexes, their association with albumin was not monitored using CD but was examined using fluorescence and PGSE diffusion NMR. Titration of BSA with any of the three metal complexes resulted in quenching of fluorescence, with the number of association sites calculated to be ~1.1, with an association constant of ~2 × 10(5) M(−1). PGSE diffusion NMR provided insights into interactions occurring with the BSA in its entirety, rather than with individual regions. Metal complex binding sites were estimated (~10 equivalent) from the diffusion data, with the average association constant for all sites ~10(2)–10(3)M(−1). These experiments highlight the information that can be elucidated from complementary spectroscopic techniques and demonstrate the usefulness of PGSE diffusion NMR in monitoring multiple weak binding sites, which is of great importance in studying drug-biomolecule interactions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12154-012-0074-1) contains supplementary material, which is available to authorized users

Biomimetic hydroxyapatite coating on glass coverslips for the assay of osteoclast activity in vitro

The osteoclast (OC) is the cell type responsible for the resorption of bone. The activity of this cell is important in the aetiology of a large number of skeletal pathologies, and also for the biocompatibility and osseointegration of orthopaedic implant materials. OC mediated acid hydrolysis of calcium phosphate from the bone matrix offers a prime means of studying the biology and activity of this cell type. We have developed a method of coating glass coverslips with a hydroxyapatite (HA)-like mineral, using a biomimetic approach. Hydroxylation followed by formation of a self assembled monolayer (SAM) using the surfactant triethoxysilylpropyl succinic anhydride (TESPSA), allowed biomimetic deposition of HA-like mineral from a simulated body fluid (SBF). The biocompatibility of the TESPSA SAM-HA coated glass coverslips was tested by culturing human mature OC present in samples of giant cell tumour of bone (GCT). Parameters of OC activity were assayed, including F-actin ring formation, release of calcium and formation of osteoclastic resorption pits, confirming that OC were able to attach to and resorb the coated surface. This approach for the preparation of HA coatings on glass coverslips could have wide applicability for the study of osteoclast behaviour in vitro.Asiri K. A. R. Wijenayak, Christopher B. Colby, Gerald J. Atkins and Peter Majewsk

Mental fatigue disturbs local processing more than global processing,Psychologische Forschung

Contains fulltext : 55605.pdf (publisher's version ) (Closed access)Focusing of attention is influenced by external features such as the presence of global or local target stimuli, but also by motivation and mood states. In the current study, we examined whether working on cognitively demanding tasks for 2 h, which induces mental fatigue, subsequently had a differential effect on global and local processing. The results showed that, compared to non-fatigued participants, fatigued participants particularly displayed compromised local processing. This indicates that mental fatigue may also manifest itself as effects on attentional focusing. The findings of this study are in line with recent ideas about the nature of fatiguerelated cognitive deficits, implying disturbances in the control over attention and behaviour.8 p

UK National Parks: A Role for Road-Pricing?

This is an electronic version of an article published in the International Journal of Sustainable Transportation [© Taylor & Francis] and the definitive version is available at: www.tandf.co.uk/journals/titles/15568318.aspThe National Parks of the United Kingdom are characterised by their beautiful countryside and spectacular rural landscapes. They are also significant trip attracting locations, the dominant transport mode being the private car, which typically accounts for 90% of all journeys made to these destinations. Excessive car use in National Parks is problematic since traffic congestion, environmental degradation, vehicle noise and parking problems serve to undermine the natural and recreational values which they are intended to promote. Though not widely explored in a rural policy context, recent literature published by key stakeholders has called for research into the potential use of innovative measures such as road pricing in National Park settings. This paper reports on the findings of in-depth interviews with Transport Officers at eleven of the fourteen UK National Park Authorities, which seek to explore the attitudes of this key group of stakeholders in regard to road pricing and the UK National Parks. The paper concludes that the complexity of the transport planning process, the significance of relationships between key stakeholders, and perceptions of existing transport conditions ‘on the ground’ in National Parks, would appear to negate the possible application of road pricing in these settings for the foreseeable future. For policy makers and planners, who have long since called for an integrated transport planning approach consisting of incentives and, crucially, disincentives, the findings question the future direction of transport planning in economically attractive, yet environmentally sensitive locations