Variation in the ability of human influenza A viruses to induce and inhibit the IFN-beta pathway

We investigated the ability of a selection of human influenza A viruses, including recent clinical isolates, to induce IFN-beta production in cultured cell lines. In contrast to the well-characterized laboratory strain A/PR/8/34, several, but not all, recent isolates of H3N2 viruses resulted in moderate IFN-beta stimulation. Through the generation of recombinant viruses, we were able to show that this is not due to a loss of the ability of the NS1 genes to suppress IFN-beta induction; indeed, the NS1 genes behaved similarly with respect to their abilities to block dsRNA signaling. Interestingly, replication of A/Sydney/5/97 virus was less Susceptible to pre-treatment with IFN-alpha than the other viruses. In contrast to the universal effect on dsRNA signaling, we noted differences in the effect of NS1 proteins on expression of interferon stimulated genes and also genes induced by a distinct pathway. The majority of NS1 proteins blocked expression From both IFN-dependent and TNF-dependent promoters by an apparent post-transcriptional mechanism. The NS1 gene of A/PR/8/34 NS1 did not confer these blocks. We noted striking differences in the Cellular localization of different influenza A virus NS1 proteins during infection, which might explain differences in biological activity. (C) 2005 Elsevier Inc. All rights reserved.

A comparative study of the effects of metal contamination on collembola in the field and in the laboratory

We examined the species diversity and abundance of Collembola at 32 sampling points along a gradient of metal contamination in a rough grassland site ( Wolverhampton, England), formerly used for the disposal of metal-rich smelting waste. Differences in the concentrations of Cd, Cu, Pb and Zn between the least and most contaminated part of the 35 metre transect were more than one order of magnitude. A gradient of Zn concentrations from 597 to 9080 mug g(-1) dry soil was found. A comparison between field concentrations of the four metals and previous studies on their relative toxicities to Collembola, suggested that Zn is likely to be responsible for any ecotoxicological effects on springtails at this site. Euedaphic ( soil dwelling) Collembola were extracted by placing soil cores into Tullgren funnels and epedaphic ( surface dwelling) species were sampled using pitfall traps. There was no obvious relationship between the total abundance, or a range of commonly used diversity indices, and Zn levels in soils. However, individual species showed considerable differences in abundance. Metal "tolerant'' (e.g., Ceratophysella denticulata) and metal "sensitive'' (e.g., Cryptopygus thermophilus) species could be identified. Epedaphic species appeared to be influenced less by metal contamination than euedaphic species. This difference is probably due to the higher mobility and lower contact with the soil pore water of epedaphic springtails in comparison to euedaphic Collembola. In an experiment exposing the standard test springtail, Folsomia candida, to soils from all 32 sampling points, adult survival and reproduction showed small but significant negative relationships with total Zn concentrations. Nevertheless, juveniles were still produced from eggs laid by females in the most contaminated soils with 9080 mug g(-1) Zn. Folsomia candida is much more sensitive to equivalent concentrations of Zn in the standard OECD soil. Thus, care should be taken in extrapolating the results of laboratory toxicity tests on metals in OECD soil to field soils, in which, the biological availability of contaminants is likely to be lower. Our studies have shown the importance of ecotoxicological effects at the species level. Although there may be no differences in overall abundance, sensitive species that are numerous in contaminated sites, and which may play important roles in decomposition("keystone species'') can be greatly reduced in numbers by pollution.

Power, nature and neoliberalism: the political ecology of water in Chile

Since the 1990s, international water sector reforms have centred heavily on economic and market approaches. In regard to water resources management, tradable water rights have been promoted, often supported by the neoliberal model adopted in Chile. Chile's 1981 Water Code was reformed to comprise a system of water rights that could be freely traded with few restrictions. International financial institutions have embraced the Chilean model, claiming that it results in more efficient water use, and potentially fosters social and environmental benefits. However, in Chile the Water Code is deeply contested. It has been criticised for being too permissive and has produced a number of problems in practice. Moreover, attempts to modify it have become the focus of a lengthy polemic debate. This paper employs a political ecology perspective to explore the socio-environmental outcomes of water management in Chile, drawing on a case study of agriculture in the semi-arid Norte Chico. The case illustrates how large-scale farmers exert greater control over water, while peasant farmers have increasingly less access. I argue that these outcomes are facilitated by the mode of water management implemented within the framework of the Water Code. Through this preliminary examination of social equity and the environmental aspects of water resources management in Chile, I suggest that the omission of these issues from the international debates on water rights markets is a cause for concern.

Gut microbial activity, implications for health and disease: the potential role of metabolite analysis

Microbial metabolism of proteins and amino acids by human gut bacteria generates a variety of compounds including phenol, indole, and sulfur compounds and branched chain fatty acids, many of which have been shown to elicit a toxic effect on the lumen. Bacterial fermentation of amino acids and proteins occurs mainly in the distal colon, a site that is often fraught with symptoms from disorders including ulcerative colitis (UC) and colorectal cancer (CRC). In contrast to carbohydrate metabolism by the gut microbiota, proteolysis is less extensively researched. Many metabolites are low molecular weight, volatile compounds. This review will summarize the use of analytical methods to detect and identify compounds in order to elucidate the relationship between specific dietary proteinaceous substrates, their corresponding metabolites, and implications for gastrointestinal health.

A mixture of trans-galactooligosaccharides reduces markers of metabolic syndrome and modulates the fecal microbiota and immune function of overweight adults

Metabolic syndrome is a set of disorders that increases the risk of developing cardiovascular disease. The gut microbiota is altered toward a less beneficial composition in overweight adults and this change can be accompanied by inflammation. Prebiotics such as galactooligosaccharides can positively modify the gut microbiota and immune system; some may also reduce blood lipids. We assessed the effect of a galactooligosaccharide mixture [Bi2 muno (B-GOS)] on markers of metabolic syndrome, gut microbiota, and immune function in 45 overweight adults with $3 risk factors associated with metabolic syndrome in a double-blind, randomized, placebo (maltodextrin)-controlled, crossover study (with a 4-wk wash-out period between interventions). Whole blood, saliva, feces, and anthropometric measurements were taken at the beginning, wk 6, and end of each 12-wk intervention period. Predominant groups of fecal bacteria were quantified and full blood count, markers of inflammation and lipid metabolism, insulin, and glucose were measured. B-GOS increased the number of fecal bifidobacteria at the expense of less desirable groups of bacteria. Increases in fecal secretory IgA and decreases in fecal calprotectin, plasma C-reactive protein, insulin, total cholesterol (TC), TG, and the TC:HDL cholesterol ratio were also observed. Administration of B-GOS to overweight adults resulted in positive effects on the composition of the gut microbiota, the immune response, and insulin, TC, and TG concentrations. B-GOSmay be a useful candidate for the enhancement of gastrointestinal health, immune function, and the reduction of metabolic syndrome risk factors in overweight adults.

SOcK, MiSTs, MASK and STicKs: the GCKIII (germinal centre kinase III) kinases and their heterologous protein–protein interactions

The GCKIII (germinal centre kinase III) subfamily of the mammalian Ste20 (sterile 20)-like group of serine/threonine protein kinases comprises SOK1 (Ste20-like/oxidant-stressresponse kinase 1), MST3 (mammalian Ste20-like kinase 3) and MST4. Initially, GCKIIIs were considered in the contexts of the regulation of mitogen-activated protein kinase cascades and apoptosis. More recently, their participation in multiprotein heterocomplexes has become apparent. In the present review, we discuss the structure and phosphorylation of GCKIIIs and then focus on their interactions with other proteins. GCKIIIs possess a highly-conserved, structured catalytic domain at the N-terminus and a less-well conserved C-terminal regulatory domain. GCKIIIs are activated by tonic autophosphorylation of a T-loop threonine residue and their phosphorylation is regulated primarily through protein serine/threonine phosphatases [especially PP2A (protein phosphatase 2A)]. The GCKIII regulatory domains are highly disorganized, but can interact with more structured proteins, particularly the CCM3 (cerebral cavernous malformation 3)/PDCD10 (programmed cell death 10) protein. We explore the role(s) of GCKIIIs (and CCM3/PDCD10) in STRIPAK (striatin-interacting phosphatase and kinase) complexes and their association with the cis-Golgi protein GOLGA2 (golgin A2; GM130). Recently, an interaction of GCKIIIs with MO25 has been identified. This exhibits similarities to the STRADα (STE20-related kinase adaptor α)–MO25 interaction (as in the LKB1–STRADα–MO25 heterotrimer) and, at least for MST3, the interaction may be enhanced by cis-autophosphorylation of its regulatory domain. In these various heterocomplexes, GCKIIIs associate with the Golgi apparatus, the centrosome and the nucleus, as well as with focal adhesions and cell junctions, and are probably involved in cell migration, polarity and proliferation. Finally, we consider the association of GCKIIIs with a number of human diseases, particularly cerebral cavernous malformations.

Child anxiety and parenting in England and Italy: the moderating role of maternal warmth

BACKGROUND: Parenting factors have been implicated in the aetiology and maintenance of child anxiety. Most research has been correlational with little experimental or longitudinal work. Cross-cultural comparison could be illuminating. A comparison of Italian and British children and their mothers was conducted. METHODS: A sample of 8- to 10-year old children, 60 Italian and 49 English, completed the Spence Child Anxiety Scale. Mothers also completed two questionnaires of parenting: the Skills of Daily Living Checklist (assessing maternal autonomy granting) and the Parent-Child Interaction Questionnaire (assessing maternal intrusiveness). Parenting was assessed in two video-recorded blindly rated mother-child interaction tasks, the 'belt-buckling tasks and the 'etch-a-sketch', providing objective indices of overcontrol, warmth, lack of autonomy granting, and overprotection. RESULTS: There were no differences between the children in overall anxiety and specific forms of anxiety. Parenting, however, was markedly different for the two countries. Compared to English mothers, on the two questionnaires, Italian mothers were significantly less autonomy granting and more intrusive; and in terms of the observed indices, a significantly greater proportion of the Italian mothers displayed a high level of both overprotection and overcontrol, and a low level of autonomy granting. Notably, Italian mothers evidenced significantly more warmth than English mothers; and maternal warmth was found to moderate the impact of self-reported maternal intrusiveness on the level of both overall child anxiety and the level of child separation anxiety; and it also moderated the relationship between both observed maternal intrusiveness and overall child anxiety and observed maternal overprotectiveness and child separation anxiety. CONCLUSIONS: Although, compared to the British mothers, the Italian mothers were more likely to evidence high levels of parenting behaviours previously found to be anxiogenic, the high levels of warmth displayed by these mothers to their children appears to have neutralised the adverse impact of these behaviours.

Institutions, unionization and voice: the relative impact of context and actors on firm level practice

Trade unions provide a voice in the way firms are run, an input into reward systems and increased security of employment. But these vary with national context. Using transnational survey evidence, this article explores the relative impact of setting, and of unions and collective bargaining, on these issues. It is found that, irrespective of context, organizations are significantly more likely to make use of compulsory redundancies in the absence of unions and collective bargaining. However, in other areas, the impact of unions appeared less pronounced than that of the wider context. The article explores the reasons behind this, and the broader policy implications thereof.

Regionalization strategy and performance: the moderating role of industry dynamism and top management team diversity

Purpose– This paper contributes to the debate about the performance implications of adopting a regional as opposed to a global strategic posture. The aim of this paper is to argue that the performance effects of a regionalization strategy vary based on the characteristics of the industry in which the MNE operates and the composition of its top management team (TMT). Design/methodology/approach– This analysis is based on a cross‐sectional dataset of 211 large European MNEs headquartered in four Western European economies at the end of 2005. Findings– Results show that firms adopting a regional orientation outperform MNEs with global strategic positioning. This positive relationship is less pronounced under conditions of industry dynamism and inter‐regional TMT diversity. Originality/value– The study contributes to our understanding of whether and under what conditions MNEs benefit from adopting a regional as opposed to a global strategic posture.

Voluntary export restraints between Britain and Japan: the case of the UK car market (1971–2002)

The rise in international markets of new, productive Japanese car manufacturers provoked intense world competition, which created serious doubts about the economic sustainability of an industry mostly dominated until the 1970s by European and North-American multinational companies. Ultimately, this crisis provoked a deep transformation of the industry, with consequences that had a permanent impact on European companies in the sector. American and later European manufacturers were successful in lobbying governments to provide protection. Using a rich source of data from the UK, I show that the ‘new trade policy’, voluntary export restraint (VER), placed on Japanese exports of new cars from 1977 to December 1999, was binding. This case study illustrates the strategies used by Japanese manufacturers to gain access to the European market through the UK market via strategic alliances and later through transplant production, against which continental European nation states were unable to fully insulate themselves. It is also shown that the policy had a profound effect on the nature of Japanese products, as Japanese firms responded to the quantity restraints by radically altering the product characteristics of their automobiles and shifting towards larger autos and new goods, to maximise their profits subject to the binding constraint.

Strategic trade policy, competition, and welfare: the case of voluntary export restraints between Britain and Japan (1971–2002)

I evaluate the voluntary export restraint placed on Japanese automobile exports from 1977 to 1999 by the UK. I show that the policy failed to assist the British domestic car industry. Instead, UK-based US multi-nationals and Japanese manufacturers were the primary beneficiaries, at a substantial cost to UK consumers. Whilst there are a number of caveats, the policy was on balance damaging to the UK economy in welfare terms.

Clinical risk factors for osteoporotic fractures in Brazilian women and men: the Brazilian Osteoporosis Study (BRAZOS)

The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older. The prevalence of fragility fractures is about 15.1% in the women and 12.8% in the men. Moreover, advanced age, sedentarism, family history of hip fracture, current smoking, recurrent falls, diabetes mellitus and poor quality of life are the main clinical risk factors associated with fragility fractures. The Brazilian Osteoporosis Study (BRAZOS) is the first epidemiological study carried out in a representative sample of Brazilian men and women aged 40 years or older with the purpose of identifying the prevalence and the main clinical risk factors (CRF) associated with osteoporotic fracture in our population. A total of 2,420 individuals (women, 70%) from 150 different cities in the five geographic regions in Brazil, and all different socio-economical classes were selected to participate in the present survey. Anthropometrical data as well as life habits, fracture history, food intake, physical activity, falls and quality of life were determined by individual quantitative interviews. The representative sampling was based on Brazilian National data provided by the 2000 and 2003 census. Low trauma fracture was defined as that resulting of a fall from standing height or less in individuals 50 years or older at specific skeletal sites: forearm, femur, ribs, vertebra and humerus. Sampling error was 2.2% with 95% confidence intervals. Logistic regression analysis models were designed having the fragility fracture as the dependent variable and all other parameters as the independent variable. Significance level was set as p < 0.05. The average of age, height and weight for men and women were 58.4 +/- 12.8 and 60.1 +/- 13.7 years, 1.67 +/- 0.08 and 1.56 +/- 0.07 m and 73.3 +/- 14.7 and 64.7 +/- 13.7 kg, respectively. About 15.1% of the women and 12.8% of the men reported fragility fractures. In the women, the main CRF associated with fractures were advanced age (OR = 1.6; 95% CI 1.06-2.4), family history of hip fracture (OR = 1.7; 95% CI 1.1-2.8), early menopause (OR = 1.7; 95% CI 1.02-2.9), sedentary lifestyle (OR = 1.6; 95% CI 1.02-2.7), poor quality of life (OR = 1.9; 95% CI 1.2-2.9), higher intake of phosphorus (OR = 1.9; 95% CI 1.2-2.9), diabetes mellitus (OR = 2.8; 95% CI 1.01-8.2), use of benzodiazepine drugs (OR = 2.0; 95% CI 1.1-3.6) and recurrent falls (OR = 2.4; 95% CI 1.2-5.0). In the men, the main CRF were poor quality of life (OR = 3.2; 95% CI 1.7-6.1), current smoking (OR = 3.5; 95% CI 1.28-9.77), diabetes mellitus (OR = 4.2; 95% CI 1.27-13.7) and sedentary lifestyle (OR = 6.3; 95% CI 1.1-36.1). Our findings suggest that CRF may contribute as an important tool to identify men and women with higher risk of osteoporotic fractures and that interventions aiming at specific risk factors (quit smoking, regular physical activity, prevention of falls) may help to manage patients to reduce their risk of fracture.

Skipping of exon 30 in C5 gene results in complete human C5 deficiency and demonstrates the importance of C5d and CUB domains for stability

The deficiency of complement C5 is rare and frequently associated with severe and recurrent infections, especially caused by Neisseria spp. We observed the absence of component C5 in the serum of 3 siblings from a Brazilian family with history of consanguinity. The patients had suffered from recurrent episodes of meningitis and other less severe infections. Sera from these patients were unable to mediate hemolytic activity either by the classical or alternative pathways and presented extremely low levels of C5 protein (13, 0.9 and 1.0 mu g/ml-normal range: 45-190 mu g/ml). Hemolytic activity could be restored by the addition of purified C5 to deficient serum. Sequencing of sibling C5 cDNA revealed a homozygous 153 bp deletion that corresponds precisely to exon 30. The parents carried the same deletion but only in one allele. Sequencing of the corresponding region in the genomic DNA revealed a C to C substitution within intron 30 and, most significantly, the substitution of GAG(4028) for GAA(4028) at the 3` end of exon 30 which is most likely responsible for skipping of exon 30. The resulting in-frame deletion in the C5 mRNA codes for a mutant C5 protein lacking residues 1289-1339. These residues map to the CUB and C5d domains of the C5 alpha chain. This deletion is expected to produce a non-functional and unstable C5 protein which is more susceptible to degradation. (C) 2009 Published by Elsevier Ltd.

Letters, authority and secrecy : The case of Karagwe in Tanzania

This paper aims to show how letters, as a genre of literacy, are used in Karagwe in Tanzania, in relation to authority and secrecy. It is shown that literacy, in the form of letters, plays an important role in the negotiation of authority. Authorities as well as ordinary people use letters according to official norms to claim or manifest authority, while grassroots forms of literacy, dominated forms, are used to resist authorities. Through secret messages and letters people find opportunities to resist that are less dangerous than open rebellion, although the effects may be limited because of the secrecy. It is also shown how children are socialized into this pattern of secrecies through literacy as they are used as messengers. When delivering secret letters and messages, they may be said to exercise a passive voice through literacy.