A possible model of benzimidazole binding to beta-tubulin disclosed by invoking an inter-domain movement.

Although it is well established that benzimidazole (BZMs) compounds exert their therapeutic effects through binding to helminth beta-tubulin and thus disrupting microtubule-based processes in the parasites, the precise location of the benzimidazole-binding site on the beta-tubulin molecule has yet to be determined. In the present study, we have used previous experimental data as cues to help identify this site. Firstly, benzimidazole resistance has been correlated with a phenylalanine-to-tyrosine substitution at position 200 of Haemonchus contortus beta-tubulin isotype-I. Secondly, site-directed mutagenesis studies, using fungi, have shown that other residues in this region of the protein can influence the interaction of benzimidazoles with beta-tubulin. However, the atomic structure of the alphabeta-tubulin dimer shows that residue 200 and the other implicated residues are buried within the protein. This poses the question: how might benzimidazoles interact with these apparently inaccessible residues? In the present study, we present a mechanism by which those residues generally believed to interact with benzimidazoles may become accessible to the drugs. Furthermore, by docking albendazole-sulphoxide into a modelled H. contortus beta-tubulin molecule we offer a structural explanation for how the mutation conferring benzimidazole resistance in nematodes may act, as well as a possible explanation for the species-specificity of benzimidazole anthelmintics.

CaII K interstellar observations towards early-type disc and halo stars - distances to intermediate- and high-velocity clouds

We compare existing high spectral resolution (R = lambda/Deltalambda similar to 40 000) Ca II Kobservations (lambda(air) = 3933.66 Angstrom) towards 88 mainly B-type stars, and new observations taken using the Intermediate dispersion Spectrograph and Imaging System (ISIS) on the William Herschel Telescope at R similar to 10 000 towards three stars taken from the Palomar-Green Survey, with 21-cm HI emission-line profiles, in order to search for optical absorption towards known intermediate- and high-velocity cloud complexes. Given certain assumptions, limits to the gas phase abundance of Ca II are estimated for the cloud components. We use the data to derive the following distances from the Galactic plane (z). (i) Tentative lower z-height limits of 2800 and 4100 pc towards complex C using lack of absorption in the spectra of HD341617 and PG 0855 + 294, respectively. (ii) A weak lower z-height of 1400 pc towards complex WA-WB using lack of absorption in EC 09470-1433 and a weak lower limit of 2470 pc using lack of absorption in EC 09452-1403. (iii) An upper z- height of 2470 pc towards a southern intermediate- velocity cloud (IVC) with v(LSR) = -55 km s(-1) using PG 2351 + 198. (iv) Detection of a possible IVC in Ca II absorption at v(LSR) = +52 km s(-1) using EC 20104-2944. No associated HI in emission is detected. At this position, normal Galactic rotation predicts velocities of up to similar to+ 25 km s(-1). The detection puts an upper z-height of 1860 pc to the cloud. (v) Tentative HI and Ca II K detections towards an IVC at similar to+70 km s(-1) in the direction of high-velocity cloud (HVC) complex WE, sightline EC 06387-8045, indicating that the IVC may be at a z-height lower than 1770 pc. (vi) Detection of Ca II K absorption in the spectrum of PG 0855 + 294 in the direction of IV20, indicating that this IVC has a z-height smaller than 4100 pc. (vii) A weak lower z-height of 4300 pc towards a small HVC with v(LSR) = +115 km s(-1) at l, b = 200degrees, + 52degrees, using lack of absorption in the Ca II K spectrum of PG 0955 + 291.

CaIIKinterstellar observations towards early-type disc and halo stars, abundances and distances of intermediate- and high-velocity clouds

We present Ca II K (lambda(air) = 3933.661 angstrom) interstellar observations towards 20 early-type stars, to place lower distance limits to intermediate- and high-velocity clouds (IHVCs) in their lines of sight. The spectra are also employed to estimate the Ca abundance in the low-velocity gas towards these objects, when combined with Leiden-Dwingeloo 21-cm HI survey data of spatial resolution 0 degrees.5. Nine of the stars, which lie towards IHVC complexes H, K and gp, were observed with the intermediate dispersion spectrograph on the Isaac Newton Telescope at a resolution R = lambda/Delta lambda of 9000 (similar to 33 km s(-1)) and signal-to-noise ratio (S/N) per pixel of 75-140. A further nine objects were observed with the Utrecht Echelle Spectrograph on the William Herschel Telescope at R = 40 000 (similar to 7.5 km s(-1)) and S/N per pixel of 10-25. Finally, two objects were observed in both Ca II K and Na I D lines using the 2D COUDE on the McDonald 2.7-m telescope at R = 35 000 (similar to 8.5 km s(-1)). The abundance of Ca II K {log(10)(A) = log(10)[N(Ca II K)]-log(10)[N(HI)]} plotted against HI column density for the objects in the current sample with heights above the Galactic plane (z) exceeding 1000 pc is found to obey the Wakker & Mathis (2000) relation. Also, the reduced column density of Ca II K as function of z is consistent with the larger sample taken from Smoker et al. (2003). Higher S/N observations than those previously taken towards HVC complex H stars HD 13256 and HILT 190 reinforce the assertion that this lies at a distance exceeding 4000 pc. No obvious absorption is detected in observations of ALS 10407 and HD 357657 towards IVC complex gp. The latter star has a spectroscopically estimated distance of similar to 2040 pc, although this was derived assuming the star lies on the main sequence and without any reddening correction being applied. Finally, no Ca II K absorption is detected towards two stars along the line of sight to complex K, namely PG 1610+529 and PG 1710+490. The latter is at a distance of similar to 700 pc, hence placing a lower distance limit to this complex, where previously only an upper distance limit of 6800 pc was available.

Inter-professional working in child protection with families with long-term and complex needs

Within the United Kingdom there is growing awareness of the need to identify and support the small number of children who are living in families experiencing multiple problems. Research indicates that adverse experiences in childhood can result in poor outcomes in adulthood in terms of lack of employment, poorer physical and mental health and increases in social problems experienced. It is acknowledged that most of these children are known to child welfare professionals and that some are referred to social services, subsequently entering the child protection system. This paper reports research conducted with twenty-eight experienced child welfare professionals. It explores their views about families known to the child protection system with long-term and complex needs in relation to the characteristics of children and their families; the process of intervention with families; and the effects of organisational arrangements on practice. The research indicates that these families are characterised by the range and depth of the problems experienced by the adults, such as domestic violence, mental health difficulties and substance misuse problems, and the need for professionals to have good inter-personal skills and access to specialist therapeutic services if families are to be supported to address their problems.

Characterizing the marine Natura 2000 network for the Atlantic region

1. One of the goals for Natura 2000, a key European Community programme of nature conservation, is to produce a network of protected areas. An analysis of the Natura 2000 marine sites proposed in the most recently agreed list for the Atlantic region (northern Portugal to Denmark, n = 298) was used to characterize the network in terms of site areas and inter-site distances. Sites were considered as part of the network when they included any of the marine Natura 2000 Annex I habitat types found in the Atlantic region (excluding lagoons).

Inter-phyla studies on neuropeptides: the potential for broad-spectrum anthelmintic and/or endectocide discovery

Flatworm, nematode and arthropod parasites have proven their ability to develop resistance to currently available chemotherapeutics. The heavy reliance on chemotherapy and the ability of target species to develop resistance has prompted the search for novel drug targets. In view of its importance to parasite/pest survival, the neuromusculature of parasitic helminths and pest arthropod species remains an attractive target for the discovery Of novel endectocide targets. Exploitation of the neuropeptidergic system in helminths and arthropods has been hampered by a limited Understanding of the functional roles of individual peptides and the structure of endogenous targets, such as receptors. Basic research into these systems has the potential to facilitate target characterization and its offshoots (screen development and drug identification). Of particular interest to parasitologists is the fact that selected neuropeptide families are common to metazoan pest species (nematodes, platyhelminths and arthropods) and fulfil specific roles in the modulation of muscle function in each of the three phyla. This article reviews the inter-phyla activity of two peptide families, the FMRFamide-like peptides and allatostatins, on motor function in helminths and arthropods and discusses the potential of neuropeptide signalling as a target system that could uncover novel endectocidal agents.

Silica grain labelling and EDX spectroscopy; evidence for inter-grain diffusion of Pt(NH3)(4)(2+) species during Pt/SiO2 catalyst preparation by ionic exchange

Labelling of silica grains and energy dispersive X-ray spectroscopy (EDX) in a TEM-FEG (field emission gun) were used to demonstrate the migration of Pt(NH3)(4)(2+) species from one grain to another during Pt/SiO2 catalyst preparation by the ion-exchange procedure.

Inter- and intrapersonal processes underlying authoritarianism: The role of social conformity and personal need for structure

Several personality constructs have been theorised to underlie right-wing authoritarianism (RWA). In samples from New Zealand and Germany (Ns = 218, 259), we tested whether these constructs can account for specific variance in RWA. In both samples, social conformity and personal need for structure were independent predictors of RWA. In Sample 2, where also openness to experience was measured, social conformity and personal need for structure fully mediated the impact of the higher-order factor of openness on RWA. Our results contribute to the integration of current approaches to the personality basis of authoritarianism. and suggest that two distinct personality processes contribute to RWA: An interpersonal process related to social conformity and an intrapersonal process related to rigid cognitive style. Copyright (C) 2009 John Wiley & Sons, Ltd.