Molecule modeling of human pentameric alpha(7) neuronal nicotinic acetylcholine receptor and its interaction with its agonist and competitive antagonist

The nicotinic Acetylcholine Receptor (nAChR) is the major class of neurotransmitter receptors that is involved in many neurodegenerative conditions such as schizophrenia, Alzheimer's and Parkinson's diseases. The N-terminal region or Ligand Binding Domain (LBD) of nAChR is located at pre- and post-synaptic nervous system, which mediates synaptic transmission. nAChR acts as the drug target for agonist and competitive antagonist molecules that modulate signal transmission at the nerve terminals. Based on Acetylcholine Binding Protein (AChBP) from Lymnea stagnalis as the structural template, the homology modeling approach was carried out to build three dimensional model of the N-terminal region of human alpha(7)nAChR. This theoretical model is an assembly of five alpha(7) subunits with 5 fold axis symmetry, constituting a channel, with the binding picket present at the interface region of the subunits. alpha-netlrotoxin is a potent nAChR competitive antagonist that readily blocks the channel resulting in paralysis. The molecular interaction of alpha-Bungarotoxin, a long chain alpha-neurotoxin from (Bungarus multicinctus) and human alpha(7)nAChR seas studied. Agonists such as acetylcholine, nicotine, which are used in it diverse array of biological activities, such as enhancements of cognitive performances, were also docked with the theoretical model of human alpha(7)nAChR. These docked complexes were analyzed further for identifying the crucial residues involved in interaction. These results provide the details of interaction of agonists and competitive antagonists with three dimensional model of the N-terminal region of human alpha(7)nAChR and thereby point to the design of novel lead compounds.

The construction industry and its resources: a research agenda

The desirable coverage of the journal is considered including the need to focus on research which can lead to positive action. Criteria for establishing the desirability of research projects are proposed and these are then applied first, to four broad issues and, secondly, to the inputs and other requirements for a well functioning industry. Some conclusions are drawn as to the research most likely to enable action to be taken to improve the industry. It is found that certain other difficulties can sometimes be dealt with by experimentation with actual projects or, where there is consensus on desirable action, by bringing pressure to bear on those able to initiate change.

Sustained monitoring of the Southern Ocean at Drake Passage: past achievements and future priorities

Drake Passage is the narrowest constriction of the Antarctic Circumpolar Current (ACC) in the Southern Ocean, with implications for global ocean circulation and climate. We review the long-term sustained monitoring programmes that have been conducted at Drake Passage, dating back to the early part of the twentieth century. Attention is drawn to numerous breakthroughs that have been made from these programmes, including (a) the first determinations of the complex ACC structure and early quantifications of its transport; (b) realization that the ACC transport is remarkably steady over interannual and longer periods, and a growing understanding of the processes responsible for this; (c) recognition of the role of coupled climate modes in dictating the horizontal transport, and the role of anthropogenic processes in this; (d) understanding of mechanisms driving changes in both the upper and lower limbs of the Southern Ocean overturning circulation, and their impacts. It is argued that monitoring of this passage remains a high priority for oceanographic and climate research, but that strategic improvements could be made concerning how this is conducted. In particular, long-term programmes should concentrate on delivering quantifications of key variables of direct relevance to large-scale environmental issues: in this context, the time-varying overturning circulation is, if anything, even more compelling a target than the ACC flow. Further, there is a need for better international resource-sharing, and improved spatio-temporal coordination of the measurements. If achieved, the improvements in understanding of important climatic issues deriving from Drake Passage monitoring can be sustained into the future.

The property development industry and sustainable urban brownfield regeneration in England: an analysis of case studies in Thames Gateway and Greater Manchester

The property development industry is a key actor in UK brownfield regeneration projects. UK policy has attempted to interlink ‘sustainable development’ and ‘sustainable brownfield’ policy agendas, which have found an additional focus through the UK government’s ‘Sustainable Communities Plan’, part of a growing international emphasis on sustainable development. This paper examines the emergence of these agendas and related policies, and the role of the property development industry in the regeneration of six differing brownfield sites, based in Thames Gateway and Greater Manchester. Using a conceptual framework, the paper investigates aspects of the sustainability of these projects and highlights key lessons from them for both the UK and overseas. The research is based on structured interviews with a variety of stakeholders, including developers, planners, consultants and community representatives to highlight emerging best practice and related policy implications.

Building networks to work: an ethnographic study of informal routes into the UK construction industry and pathways for migrant up-skilling

The UK construction industry labour market is characterised by high levels of self-employment, sub-contracting, informality and flexibility. A corollary of this, and a sign of the increasing globalisation of construction, has been an increasing reliance on migrant labour, particularly that from the Eastern European Accession states. Yet, little is known about how their experiences within and outside of work shape their work in the construction sector. In this context better qualitative understandings of the social and communication networks through which migrant workers gain employment, create routes through the sector and develop their role/career are needed. We draw on two examples from a short-term ethnographic study of migrant construction worker employment experiences and practices in the town of Crewe in Cheshire, UK, to demonstrate how informal networks intersect with formal elements of the sector to facilitate both recruitment and up-skilling. Such research knowledge, we argue, offers new evidence of the importance of attending to migrant worker’s own experiences in the development of more transparent recruitment processes.

Scoring rules and competitive behavior in best value construction auctions

This paper examines the extent to which engineers can influence the competitive behavior of bidders in Best Value or multi-attribute construction auctions, where both the (dollar) bid and technical non-price criteria are scored according to a scoring rule. From a sample of Spanish construction auctions with a variety of bid scoring rules, it is found that bidders are influenced by the auction rules in significant and predictable ways. The bid score weighting, bid scoring formula and abnormally low bid criterion are variables likely to influence the competitiveness of bidders in terms of both their aggressive/conservative bidding and concentration/dispersion of bids. Revealing the influence of the bid scoring rules and their magnitude on bidders’ competitive behavior opens the door for the engineer to condition bidder competitive behavior in such a way as to provide the balance needed to achieve the owner’s desired strategic outcomes.

Competitive exclusion by Bacillus subtilis spores of Salmonella enterica serotype Enteritidis and Clostridium perfringens in young chickens

Cost effective control of avian diseases and food borne pathogens remains a high priority for all sectors of the poultry industry with cleansing and disinfection, vaccination and competitive exclusion approaches being used widely. Previous studies showed that Bacillus subtilis PY79(hr) was an effective competitive exclusion agent for use in poultry to control avian pathogenic Escherichia coli serotype O78:K80. Here we report experiments that were undertaken to test the efficacy of B. subtilis PY79(hr) in the control of Salmonella enterica serotype Enteritidis and Clostridium perfringens in young chickens. To do this, 1-day-old and 20-day-old specific pathogen free (SPF) chicks were dosed with a suspension of B. subtilis spores prior to challenge with S. Enteritidis (S1400) and C. perfringens, respectively. For both challenge models, a single oral inoculum of 1 x 10(9) spores given 24 h prior to challenge was sufficient to suppress colonisation and persistence of both S. Enteritidis and C perfringens. In particular, the faecal shedding of S. Enteritidis, as measured by a semi-quantitative cloacal swabbing technique, was reduced significantly for the 36 days duration of the experiment. B. subtilis persisted in the intestine although with decreasing numbers over the same period. These data add further evidence that B. subtilis spores may be effective agents in the control of avian diseases and food borne pathogens.