Mutation of toxB and a truncated version of the efa-1 gene in Escherichia coli O157 : H7 influences the expression and secretion of locus of enterocyte effacement-encoded proteins but not intestinal colonization in calves or sheep

Enterohemorrhagic Escherichia coli (EHEC) strains comprise a broad group of bacteria, some of which cause attaching and effacing (AE) lesions and enteritis in humans and animals. Non-O157:H7 EHEC strains contain the gene efa-1 (referred to in previous publications as efa1), which influences adherence to cultured epithelial cells. An almost identical gene in enteropathogenic E. coli (lifA) mediates the inhibition of lymphocyte proliferation and proinflammatory cytokine synthesis. We have shown previously that significantly lower numbers of EHEC 05 and 0111 efa-1 mutants are shed in feces following experimental infection in calves and that these mutants exhibit reduced adherence to intestinal epithelia compared with isogenic wild-type strains. E. coli O157:H7 strains lack efa-1 but encode a homolog on the pO157 plasmid (toxB/l7095) and contain a truncated version of the efa-1 gene (efa-1'/z4332 in O island 122 of the EDL933 chromosome). Here we report that E. coli O157:H7 toxB and efa-1' single and double mutants exhibit reduced adherence to cultured epithelial cells and show reduced expression and secretion of proteins encoded by the locus of enterocyte effacement (LEE), which plays a key role in the host-cell interactions of EHEC. The activity of LEE1, LEE4, and LEE5 promoters was not significantly altered in E. coli O157:H7 strains harboring toxB or efa-1' mutations, indicating that the effect on the expression of LEE-encoded secreted proteins occurs at a posttranscriptional level. Despite affecting type III secretion, mutation of toxB and efa-1' did not significantly affect the course of fecal shedding of E. coli O157:H7 following experimental inoculation of 10- to 14-day-old calves or 6-week-old sheep. Mutation of tir caused a significant reduction in fecal shedding of E. coli O157:H7 in calves, indicating that the formation of AE lesions is important for colonization of the bovine intestine.

Environmental regulation and colonization attributes of the long polar fimbriae (LPF) of Escherichia coli O157:H7

The ability of Escherichia coli O157:H7 to colonize the intestinal epithelia is dependent on the expression of intimin and other adhesins. The chromosome of E. coli O157:H7 carries two loci encoding long polar fimbriae (LPF). These fimbriae mediate adherence to epithelial cells and are associated with colonization of the intestine. In order to increase our knowledge about the conditions controlling their expression and their role in colonization of an animal model, the environmental cues that promote expression of lpf genes and the role of E. coli O157:H7 LPF in intestinal colonization of lambs were investigated. We found that expression of lpf1 was regulated in response to growth phase, osmolarity, and pH; that lpf2 transcription was stimulated during late exponential growth and iron depletion; and that LPF impacts the ability of E. coli O157:H7 to persist in the intestine of infected 6-week-old lambs.

Response kinetics in the complex chemotaxis signalling pathway of Rhodobacter sphaeroides

Chemotaxis is one of the best characterised signalling systems in biology. It is the mechanism by which bacteria move towards optimal environments and is implicated in biofilm formation, pathogenesis and symbiosis. The properties of the bacterial chemosensory response have been described in detail for the single chemosensory pathway of Escherichia coli. We have characterised the properties of the chemosensory response of Rhodobacter sphaeroides, an -proteobacterium with multiple chemotaxis pathways, under two growth conditions allowing the effects of protein expression levels and cell architecture to be investigated. Using tethered cell assays we measured the responses of the system to step changes in concentration of the attractant propionate and show that, independently of the growth conditions, R. sphaeroides is chemotactic over at least five orders of magnitude and has a sensing profile following Weber’s law. Mathematical modelling also shows that, like E. coli, R. sphaeroides is capable of showing Fold-Change Detection (FCD). Our results indicate that general features of bacterial chemotaxis such as the range and sensitivity of detection, adaptation times, adherence to Weber’s law and the presence of FCD may be integral features of chemotaxis systems in general, regardless of network complexity, protein expression levels and cellular architecture across different species.

Increasing doxorubicin activity against breast cancer cells using PPARγ-ligands and by exploiting circadian rhythms

Doxorubicin is effective against breast cancer, but its major side effect is cardiotoxicity. The aim of this study was to determine whether the efficacy of doxorubicin on cancer cells could be increased in combination with PPARγ agonists or chrono-optimization by exploiting the diurnal cycle. We determined cell toxicity using MCF-7 cancer cells, neonatal rat cardiac myocytes and fibroblasts in this study. Doxorubicin damages the contractile filaments of cardiac myocytes and affects cardiac fibroblasts by significantly inhibiting collagen production and proliferation at the level of the cell cycle. Cyclin D1 protein levels decreased significantly following doxorubicin treatment indicative of a G1 /S arrest. PPARγ agonists with doxorubicin increased the toxicity to MCF-7 cancer cells without affecting cardiac cells. Rosiglitazone and ciglitazone both enhanced anti-cancer activity when combined with doxorubicin (e.g. 50% cell death for doxorubicin at 0.1 μM compared to 80% cell death when combined with rosiglitazone). Thus, the therapeutic dose of doxorubicin could be reduced by 20-fold through combination with the PPARγ agonists, thereby reducing adverse effects on the heart. The presence of melatonin also significantly increased doxorubicin toxicity, in cardiac fibroblasts (1 μM melatonin) but not in MCF-7 cells. Our data show, for the first time, that circadian rhythms play an important role in doxorubicin toxicity in the myocardium; doxorubicin should be administered mid-morning, when circulating levels of melatonin are low, and in combination with rosiglitazone to increase therapeutic efficacy in cancer cells while reducing the toxic effects on the heart.

Regional climate change mitigation with crops: context and assessment

The intention of this review is to place crop albedo biogeoengineering in the wider picture of climate manipulation. Crop biogeoengineering is considered within the context of the long-term modification of the land surface for agriculture over several thousand years. Biogeoengineering is also critiqued in relation to other geoengineering schemes in terms of mitigation power and adherence to social principles for geoengineering. Although its impact is small and regional, crop biogeoengineering could be a useful and inexpensive component of an ensemble of geoengineering schemes to provide temperature mitigation. The method should not detrimentally affect food security and there may even be positive impacts on crop productivity, although more laboratory and field research is required in this area to understand the underlying mechanisms.

The lottery-panel task for bi-dimensional parameter-free elicitation of risk attitudes

We propose first, a simple task for the eliciting attitudes toward risky choice, the SGG lottery-panel task, which consists in a series of lotteries constructed to compensate riskier options with higher risk-return trade-offs. Using Principal Component Analysis technique, we show that the SGG lottery-panel task is capable of capturing two dimensions of individual risky decision making i.e. subjects’ average risk taking and their sensitivity towards variations in risk-return. From the results of a large experimental dataset, we confirm that the task systematically captures a number of regularities such as: A tendency to risk averse behavior (only around 10% of choices are compatible with risk neutrality); An attraction to certain payoffs compared to low risk lotteries, compatible with over-(under-) weighting of small (large) probabilities predicted in PT and; Gender differences, i.e. males being consistently less risk averse than females but both genders being similarly responsive to the increases in risk-premium. Another interesting result is that in hypothetical choices most individuals increase their risk taking responding to the increase in return to risk, as predicted by PT, while across panels with real rewards we see even more changes, but opposite to the expected pattern of riskier choices for higher risk-returns. Therefore, we conclude from our data that an “economic anomaly” emerges in the real reward choices opposite to the hypothetical choices. These findings are in line with Camerer's (1995) view that although in many domains, paid subjects probably do exert extra mental effort which improves their performance, choice over money gambles is not likely to be a domain in which effort will improve adherence to rational axioms (p. 635). Finally, we demonstrate that both dimensions of risk attitudes, average risk taking and sensitivity towards variations in the return to risk, are desirable not only to describe behavior under risk but also to explain behavior in other contexts, as illustrated by an example. In the second study, we propose three additional treatments intended to elicit risk attitudes under high stakes and mixed outcome (gains and losses) lotteries. Using a dataset obtained from a hypothetical implementation of the tasks we show that the new treatments are able to capture both dimensions of risk attitudes. This new dataset allows us to describe several regularities, both at the aggregate and within-subjects level. We find that in every treatment over 70% of choices show some degree of risk aversion and only between 0.6% and 15.3% of individuals are consistently risk neutral within the same treatment. We also confirm the existence of gender differences in the degree of risk taking, that is, in all treatments females prefer safer lotteries compared to males. Regarding our second dimension of risk attitudes we observe, in all treatments, an increase in risk taking in response to risk premium increases. Treatment comparisons reveal other regularities, such as a lower degree of risk taking in large stake treatments compared to low stake treatments and a lower degree of risk taking when losses are incorporated into the large stake lotteries. Results that are compatible with previous findings in the literature, for stake size effects (e.g., Binswanger, 1980; Antoni Bosch-Domènech & Silvestre, 1999; Hogarth & Einhorn, 1990; Holt & Laury, 2002; Kachelmeier & Shehata, 1992; Kühberger et al., 1999; B. J. Weber & Chapman, 2005; Wik et al., 2007) and domain effect (e.g., Brooks and Zank, 2005, Schoemaker, 1990, Wik et al., 2007). Whereas for small stake treatments, we find that the effect of incorporating losses into the outcomes is not so clear. At the aggregate level an increase in risk taking is observed, but also more dispersion in the choices, whilst at the within-subjects level the effect weakens. Finally, regarding responses to risk premium, we find that compared to only gains treatments sensitivity is lower in the mixed lotteries treatments (SL and LL). In general sensitivity to risk-return is more affected by the domain than the stake size. After having described the properties of risk attitudes as captured by the SGG risk elicitation task and its three new versions, it is important to recall that the danger of using unidimensional descriptions of risk attitudes goes beyond the incompatibility with modern economic theories like PT, CPT etc., all of which call for tests with multiple degrees of freedom. Being faithful to this recommendation, the contribution of this essay is an empirically and endogenously determined bi-dimensional specification of risk attitudes, useful to describe behavior under uncertainty and to explain behavior in other contexts. Hopefully, this will contribute to create large datasets containing a multidimensional description of individual risk attitudes, while at the same time allowing for a robust context, compatible with present and even future more complex descriptions of human attitudes towards risk.

Poetry on Pre-Raphaelite principles: science, nature and knowledge in William Michael Rossetti’s 'Fancies at Leisure' and 'Mrs. Holmes Grey'

This article demonstrates how early Pre-Raphaelite poetry worked according to the principle that art should be modelled on science theorised by the Pre-Raphaelites in their early essays. As the main theorists (rather than practitioners) of Pre-Raphaelite art, F. G. Stephens and William Michael Rossetti defined the Pre-Raphaelite project in terms of observation, investigation, experiment, the “adherence to fact” and the “search after truth”. In the hands of the early Pre-Raphaelite poets, and particularly Rossetti himself, poetry too becomes a mode of scientific enquiry into the natural world, the nature of observation, human psychology and medical practice.

Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci

BACKGROUND: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics. OBJECTIVE: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI). DESIGN: We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models. RESULTS: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI (β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations. CONCLUSIONS: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up.

Effects of increased wholegrain consumption on immune and inflammatory markers in healthy low habitual wholegrain consumers

Purpose Wholegrain (WG) consumption is associated with reduced risk of cardiovascular disease, but clinical data on inflammation and immune function is either conflicting or limited. The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/d on markers of inflammation and glucose metabolism and on phenotypic and functional aspects of the immune system, in healthy, middle-aged adults with low habitual WG intake. Methods Subjects consumed a diet high in WG (> 80 g/d) or low in WG (< 16 g/d, refined grain diet) in a crossover study, with 6-week intervention periods, separated by a 4-week washout. Adherence to the dietary regimes was achieved by dietary advice and provision of a range of food products, with compliance verified through analysis of plasma alkylresorcinols (ARs). Results On the WG intervention, WG consumption reached 168 g/d (P < 0.001), accompanied by an increase in plasma ARs (P < 0.001) and fibre intake (P < 0.001), without affecting other aspects of dietary intake. On the WG arm there were trends for lower ex vivo activation of CD4+ T cells and circulating concentrations of IL-10, C-reactive protein, C-peptide, insulin and plasminogen activator inhibitor-1. The percentage of CD4+ central memory T cells and circulating levels of adipsin tended to increase during the WG intervention. Conclusions Despite the dramatic increase in WG consumption, there were no effects on phenotypic or functional immune parameters, markers of inflammation or metabolic markers.

Prebiotics modulate the effects of antibiotics on gut microbial diversity and functioning in vitro

Intestinal bacteria carry out many fundamental roles, such as the fermentation of non-digestible dietary carbohydrates to produce short chain fatty acids (SCFAs), which can affect host energy levels and gut hormone regulation. Understanding how to manage this ecosystem to improve human health is an important but challenging goal. Antibiotics are the front line of defence against pathogens, but in turn they have adverse effects on indigenous microbial diversity and function. Here, we have investigated whether dietary supplementation—another method used to modulate gut composition and function—could be used to ameliorate the side effects of antibiotics. We perturbed gut bacterial communities with gentamicin and ampicillin in anaerobic batch cultures in vitro. Cultures were supplemented with either pectin (a non-fermentable fibre), inulin (a commonly used prebiotic that promotes the growth of beneficial bacteria) or neither. Although antibiotics often negated the beneficial effects of dietary supplementation, in some treatment combinations, notably ampicillin and inulin, dietary supplementation ameliorated the effects of antibiotics. There is therefore potential for using supplements to lessen the adverse effects of antibiotics. Further knowledge of such mechanisms could lead to better therapeutic manipulation of the human gut microbiota.

Endocannabinoid signaling in autism

Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions). In the last 25 years a good deal of information has been accumulated on the main components of the “endocannabinoid (eCB) system”, a rather complex ensemble of lipid signals (“endocannabinoids”), their target receptors, purported transporters, and metabolic enzymes. It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders. Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.

An entirely new land? Italy’s post-war culture and its fascist past

Scholarship has for decades emphasised the significant continuities in Italian culture and society after Fascism, calling into question the rhetoric of post-war renewal. This essay proposes a reassessment of that rhetoric through the analysis of five key metaphors with which Italian intellectuals represented national recovery after 1945: parenthesis, disease, flood, childhood, and discovery. While the current critical consensus would lead us to expect a cultural conversation characterised by repression and evasion, an analysis of these five post-war metaphors instead reveals both a penetrating re-assessment of Italian culture after Fascism and an earnest adherence to the cause of national re-vitalisation. Foregrounding the inter-relation of Italy’s prospects for change and its continuities with Fascism, these metaphors suggest that post-war Italian intellectuals conceived of their country’s hopes for renewal, as well as its connections to the recent past, in terms that transcend the binary division favoured in many historical accounts.

Gendered struggles over land: shifting inheritance practices among the Serer in rural Senegal

Although women's land rights are often affirmed unequivocally in constitutions and international human rights conventions in many African countries, customary practices usually prevail on the ground and often deny women's land inheritance. Yet land inheritance often goes unnoticed in wider policy and development initiatives to promote women's equal access to land. This paper draws on feminist ethnographic research among the Serer ethnic group in two contrasting rural communities in Senegal. Through analysis of land governance, power relations and 'technologies of the self', this article shows how land inheritance rights are contingent on the specific effects of intersectionality in particular places. The contradictions of legal pluralism, greater adherence to Islam and decentralisation led to greater application of patrilineal inheritance practices. Gender, religion and ethnicity intersected with individuals' marital position, status, generation and socio-ecological change to constrain land inheritance rights for women, particularly daughters, and widows who had been in polygamous unions and who remarried. Although some women were aware that they were legally entitled to inherit a share of the land, they tended not to 'demand their rights'. In participatory workshops, micro-scale shifts in women's and men's positionings reveal a recognition of the gender discriminatory nature of customary and Islamic law and a desire to 'change with the times'. While the effects of 'reverse' discourses are ambiguous and potentially reinforce prevailing patriarchal power regimes, 'counter' discourses, which emerged in participatory spaces, may challenge customary practices and move closer to a rights-based approach to gender equality and women's land inheritance.

Analysis of dietary pattern impact on weight status for personalised nutrition through on-line advice: the Food4Me Spanish cohort

Obesity prevalence is increasing. The management of this condition requires a detailed analysis of the global risk factors in order to develop personalised advice. This study is aimed to identify current dietary patterns and habits in Spanish population interested in personalised nutrition and investigate associations with weight status. Self-reported dietary and anthropometrical data from the Spanish participants in the Food4Me study, were used in a multidimensional exploratory analysis to define specific dietary profiles. Two opposing factors were obtained according to food groups’ intake: Factor 1 characterised by a more frequent consumption of traditionally considered unhealthy foods; and Factor 2, where the consumption of “Mediterranean diet” foods was prevalent. Factor 1 showed a direct relationship with BMI (β = 0.226; r2 = 0.259; p < 0.001), while the association with Factor 2 was inverse (β = −0.037; r2 = 0.230; p = 0.348). A total of four categories were defined (Prudent, Healthy, Western, and Compensatory) through classification of the sample in higher or lower adherence to each factor and combining the possibilities. Western and Compensatory dietary patterns, which were characterized by high-density foods consumption, showed positive associations with overweight prevalence. Further analysis showed that prevention of overweight must focus on limiting the intake of known deleterious foods rather than exclusively enhance healthy products.

The changing influence of societal culture on job satisfaction across Europe

This paper contributes to the growing multidisciplinary body of literature on subjective well-being by investigating the longitudinal stability and impact of societal cultural values (SCVs) – as opposed to the more common organizational values – on job satisfaction. It is assumed that SCVs evolve slowly; hence, their impact on job satisfaction is likely to remain stable over time. False adherence to this assumption could cause misalignment between organizational policies/practices and expectations formed by societal culture, decreasing job satisfaction and adversely affecting productivity, competiveness and prosperity. Four waves of the European Values Study are used to examine whether SCVs have evolved and their impacts on job satisfaction over a relatively short time: 1981–2008. SCVs are parameterized through reference to traditional vs secular-rational, and survival vs self-expression value continuums. Results indicate that the strength of many SCVs has declined, the impacts of traditional societal values on job satisfaction have remained fairly constant, and the impacts of survival societal values on job satisfaction have declined substantially over this sample period. These reductions in SCVs amplify the importance of accounting for such changes when designing new or adjusting existing policies/practices to enhance job satisfaction and stimulate improvements in productivity, competitiveness and prosperity.