The evolutionary basis for differences between the immune systems of man, mouse, pig and ruminants

Studying the pathogenesis of an infectious disease like colibacillosis requires an understanding of the responses of target hosts to the organism both as a pathogen and as a commensal. The mucosal immune system constitutes the primary line of defence against luminal micro-organisms. The immunoglobulin-superfamily-based adaptive immune system evolved in the earliest jawed vertebrates, and the adaptive and innate immune system of humans, mice, pigs and ruminants co-evolved in common ancestors for approximately 300 million years. The divergence occurred only 100 mya and, as a consequence, most of the fundamental immunological mechanisms are very similar. However, since pressure on the immune system comes from rapidly evolving pathogens, immune systems must also evolve rapidly to maintain the ability of the host to survive and reproduce. As a consequence, there are a number of areas of detail where mammalian immune systems have diverged markedly from each other, such that results obtained in one species are not always immediately transferable to another. Thus, animal models of specific diseases need to be selected carefully, and the results interpreted with caution. Selection is made simpler where specific host species like cattle and pigs can be both target species and reservoirs for human disease, as in infections with Escherichia coli.

The origins of domestic horses in north-west Europe: new direct dates on the horses of Newgrange, Ireland

This paper presents direct radiocarbon measurements on horse skeletal remains from the Beaker period settlement at the site of Newgrange in Ireland, finds which have previously been argued as the earliest domestic horses in Ireland. The new determinations date the horse remains to the Irish Iron Age and shed important new light on the introduction of domestic horses to Ireland and to north-west Europe more generally. Although the new dates undermine the idea for the introduction of horses as part of a ‘Beaker package’, the early use of horse is not well defined archaeologically or chronologically and the earliest use of domestic horses in Ireland and Britain is still uncertain. This paper also identifies evidence for heavy bitting damage on the Iron Age Newgrange horse teeth and presents some possible parallels between the evidence from Newgrange and that at Tara, which has been previously linked with kingship rituals

From wild horses to domestic horses: a European perspective

There is a period of some 5000 years or so in the prehistory of Europe when horse populations were greatly depleted and perhaps even disappeared in many places. Before this time, during the Upper Palaeolithic, wild horses were common; after, during the Bronze Age, domestic horses were being raised and used across Europe. What happened in between is uncertain, in part because of the sketchy archaeological record. Debates continue as to the origins (the when, where and how) of Europe's domestic horses, including whether horse husbandry dispersed only from habitats favourable to horses on the Eurasian steppes or whether there was local domestication in temperate Europe. This paper reviews the evidence for the transition from wild horses to domestic horses in Europe.

Catch-up strategies in the Indian auto components industry: domestic firms’ responses to market liberalization

Market liberalization in emerging-market economies and the entry of multinational firms spur significant changes to the industry/institutional environment faced by domestic firms. Prior studies have described how such changes tend to be disruptive to the relatively backward domestic firms, and negatively affect their performance and survival prospects. In this paper, we study how domestic supplier firms may adapt and continue to perform, as market liberalization progresses, through catch-up strategies aimed at integrating with the industry's global value chain. Drawing on internalization theory and the literatures on upgrading and catch-up processes, learning and relational networks, we hypothesize that, for continued performance, domestic supplier firms need to adapt their strategies from catching up initially through technology licensing/collaborations and joint ventures with multinational enterprises (MNEs) to also developing strong customer relationships with downstream firms (especially MNEs). Further, we propose that successful catch-up through these two strategies lays the foundation for a strategy of knowledge creation during the integration of domestic industry with the global value chain. Our analysis of data from the auto components industry in India during the period 1992–2002, that is, the decade since liberalization began in 1991, offers support for our hypotheses.

Ranging characteristics of the domestic cat (Felis catus) in an urban environment

In many countries, high densities of domestic cats (Felis catus) are found in urban habitats where they have the potential to exert considerable predation pressure on their prey. However, little is known of the ranging behaviour of cats in the UK. Twenty cats in suburban Reading, UK, were fitted with GPS trackers to quantify movement patterns. Cats were monitored during the summer and winter for an average of 6.8 24 h periods per season. Mean daily area ranged (95 % MCP) was 1.94 ha. Including all fixes, mean maximum area ranged was 6.88 ha. These are broadly comparable to those observed in urban areas in other countries. Daily area ranged was not affected by the cat’s sex or the season, but was significantly larger at night than during the day. There was no relationship between area ranged and habitat availability. Taking available habitat into account, cat ranging area contained significantly more garden and other green space than urban habitats. If cats were shown to be negatively affecting prey populations, one mitigation option for consideration in housing developments proposed near important wildlife sites would be to incorporate a ‘buffer zone’ in which cat ownership was not permitted. Absolute maximum daily area ranged by a cat in this study was 33.78 ha. This would correspond to an exclusory limit of approximately 300–400 m to minimise the negative effects of cat predation, but this may need to be larger if cat ranging behaviour is negatively affected by population density

Demand response from the non-domestic sector: early UK experiences and future opportunities

Demand response is believed by some to become a major contributor towards system balancing in future electricity networks. Shifting or reducing demand at critical moments can reduce the need for generation capacity, help with the integration of renewables, support more efficient system operation and thereby potentially lead to cost and carbon reductions for the entire energy system. In this paper we review the nature of the response resource of consumers from different non-domestic sectors in the UK, based on extensive half hourly demand profiles and observed demand responses. We further explore the potential to increase the demand response capacity through changes in the regulatory and market environment. The analysis suggests that present demand response measures tend to stimulate stand-by generation capacity in preference to load shifting and we propose that extended response times may favour load based demand response, especially in sectors with significant thermal loads.

A metabolic system-wide characterisation of the pig: a model for human physiology

The pig is a single-stomached omnivorous mammal and is an important model of human disease and nutrition. As such, it is necessary to establish a metabolic framework from which pathology-based variation can be compared. Here, a combination of one and two-dimensional 1H and 13C nuclear magnetic resonance spectroscopy (NMR) and high-resolution magic angle spinning (HR-MAS) NMR was used to provide a systems overview of porcine metabolism via characterisation of the urine, serum, liver and kidney metabolomes. The metabolites observed in each of these biological compartments were found to be qualitatively comparable to the metabolic signature of the same biological matrices in humans and rodents. The data were modelled using a combination of principal components analysis and Venn diagram mapping. Urine represented the most metabolically distinct biological compartment studied, with a relatively greater number of NMR detectable metabolites present, many of which are implicated in gut-microbial co-metabolic processes. The major interspecies differences observed were in the phase II conjugation of extra-genomic metabolites; the pig was observed to conjugate p-cresol, a gut microbial metabolite of tyrosine, with glucuronide rather than sulfate as seen in man. These observations are important to note when considering the translatability of experimental data derived from porcine models.

Domestic energy models: complexities in defining specific tools

The domestic (residential) sector accounts for 30% of the world’s energy consumption hence plays a substantial role in energy management and CO2 emissions reduction efforts. Energy models have been generally developed to mitigate the impact of climate change and for the sustainable management and planning of energy resources. Although there are different models and model categories, they are generally categorised into top down and bottom up. Significantly, top down models are based on aggregated data while bottom up models are based on disaggregated data. These approaches create fundamental differences which have been the centre of debate since the 1970’s. These differences have led to noticeable discrepancies in results which have led to authors arguing that the models are of a more complementary than a substituting nature. As a result developing methods suggest that there is the need to integrate either the two models (bottom up − top down) or aspects that combine two bottom up models or an upgrade of top down models to compensate for the documented limitations. Diverse schools of thought argue in favour of these integrations – currently known as hybrid models. In this paper complexities of identifying country specific and/or generic domestic energy models and their applications in different countries have been critically reviewed. Predominantly from the review it is evident that most of these methods have been adapted and used in the ‘western world’ with practically no such applications in Africa.

International terrorism, domestic political instability, and the escalation effect

What are the main causes of international terrorism? Despite the meticulous examination of various candidate explanations, existing estimates still diverge in sign, size, and significance. This article puts forward a novel explanation and supporting evidence. We argue that domestic political instability provides the learning environment needed to successfully execute international terror attacks. Using a yearly panel of 123 countries over 1973–2003, we find that the occurrence of civil wars increases fatalities and the number of international terrorist acts by 45%. These results hold for alternative indicators of political instability, estimators, subsamples, subperiods, and accounting for competing explanations.

Management compensation systems in MNCs and domestic firms. Cross-national empirical evidence

• This is a study of the relationship between institutional settings and managerial compensation systems, based on extensive cross-national survey evidence. • We compare differences in practices between Multinational Corporations (MNCs) and domestic firms across a range of capitalist archetypes. • We find that MNCs are more likely to promote compensation systems that incentivise managers in line with organisational performance compared to domestic firms. Our findings also reveal persistent diversity reflecting firm type and institutional setting. We find that the gap between MNCs and domestic firms in terms of the usage of incentive-related compensation is less pronounced in Liberal Market Economies than in other settings. This suggests that it is a combination of being an MNC and the specific home locale that moulds approaches to managerial compensation. This reflects considerable hybridisation of practices within and between settings.

Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways

The protease activated receptor-2 (PAR-2) belongs to a family of G-protein-coupled receptors that are activated by proteolysis. Trypsin cleaves PAR-2, exposing an N-terminal tethered ligand (SLIGRL) that activates the receptor. Messenger RNA (mRNA) for PAR-2 was found in guinea pig airway tissue by reverse transcription-polymerase chain reaction, and PAR-2 was found by immunohistochemistry in airway epithelial and smooth-muscle cells. In anesthetized guinea pigs, trypsin and SLIGRL-NH(2) (given intratracheally or intravenously) caused a bronchoconstriction that was inhibited by the combination of tachykinin-NK(1) and -NK(2) receptor antagonists and was potentiated by inhibition of nitric oxide synthase (NOS). Trypsin and SLIGRL-NH(2) relaxed isolated trachea and main bronchi, and contracted intrapulmonary bronchi. Relaxation of main bronchi was abolished or reversed to contraction by removal of epithelium, administration of indomethacin, and NOS inhibition. PAR-1, PAR-3, and PAR-4 were not involved in the bronchomotor action of either trypsin or SLIGRL-NH(2), because ligands of these receptors were inactive either in vitro or in vivo, and because thrombin (a PAR-1 and PAR-3 agonist) did not show cross-desensitization with PAR-2 agonists in vivo. Thus, we have localized PAR-2 to the guinea-pig airways, and have shown that activation of PAR-2 causes multiple motor effects in these airways, including in vivo bronchoconstriction, which is in part mediated by a neural mechanism.

An analysis of UK policies for domestic energy reduction using an agent based tool

This paper introduces a new agent-based model, which incorporates the actions of individual homeowners in a long-term domestic stock model, and details how it was applied in energy policy analysis. The results indicate that current policies are likely to fall significantly short of the 80% target and suggest that current subsidy levels need re-examining. In the model, current subsidy levels appear to offer too much support to some technologies, which in turn leads to the suppression of other technologies that have a greater energy saving potential. The model can be used by policy makers to develop further scenarios to find alternative, more effective, sets of policy measures. The model is currently limited to the owner-occupied stock in England, although it can be expanded, subject to the availability of data.

Sequence analysis of a CTX-M-1 IncI1 plasmid found in Salmonella enterica 4,5,12,i:-, Escherichia coli and Klebsiella pneumoniae on a single UK pig farm

OBJECTIVES: In 2009, CTX-M Enterobacteriaceae and Salmonella isolates were recovered from a UK pig farm, prompting studies into the dissemination of the resistance and to establish any relationships between the isolates. METHODS: PFGE was used to elucidate clonal relationships between isolates whilst plasmid profiling, restriction analysis, sequencing and PCR were used to characterize the CTX-M-harbouring plasmids. RESULTS: Escherichia coli, Klebsiella pneumoniae and Salmonella 4,5,12:i:- and Bovismorbificans resistant to cefotaxime (n = 65) were recovered and 63 were shown by PCR to harbour a group 1 CTX-M gene. The harbouring hosts were diverse, but the group 1 CTX-M plasmids were common. Three sequenced CTX-M plasmids from E. coli, K. pneumoniae and Salmonella enterica serotype 4,5,12:i:- were identical except for seven mutations and highly similar to IncI1 plasmid ColIb-P9. Two antimicrobial resistance regions were identified: one inserted upstream of yacABC harbouring ISCR2 transposases, sul2 and floR; and the other inserted within shfB of the pilV shufflon harbouring the ISEcp1 transposase followed by blaCTX-M-1. CONCLUSIONS: These data suggest that an ST108 IncI1 plasmid encoding a blaCTX-M-1 gene had disseminated across multiple genera on this farm, an example of horizontal gene transfer of the blaCTX-M-1 gene.