233 research outputs found

    Letters and records of the dissenting congregations: David Crosley, Cripplegate and Baptist Church life

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    The original publication is available at www.springerlink.comInternational audienceThis chapter examines the status and function of letters in manuscript records of dissenting Churches of the post-Toleration years, concentrating on the correspondence of the Baptist Church of Cripplegate. The letters are placed in the context of controversies about Church government and discipline and the rhetoric used during the scandal caused by the excommunication of its Northern minister David Crosley for drinking, lying and adultery is assessed. In doing so, the chapter pays particular attention to the epistolary exchanges between metropolitan and provincial congregations and to what they reveal about conceptions of the Baptist ministry

    Voice, autonomy and utopian desire in participatory film-making with young refugees

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    This article is a reflection on what reflexive documentary scholars call the ‘moral dimension’ (Nash 2012: 318) of a participatory filmmaking project with refugee young people, who wanted to make a film to support other new young arrivals in the process of making home in Scotland. In the first part, we highlight some of the challenges of collaborating with refugee young people, in light of the often de-humanising representations of refugees in mainstream media and the danger of the triple conflation of authenticity-voice-pain in academic narratives about refugees. In the second part, we show how honouring young people’s desire to convey the hopeful aspects of making home, emerged as a key pedagogical strategy to affirm their expert position and encourage their participation in the project. Revisiting key moments of learning and interaction, we demonstrate how young people’s process of ‘finding a voice’ in moment-by-moment filmmaking practice was not a linear, developmental process towards ‘pure’ individual empowerment and singular artistic expression. Their participation in shaping their visual (self-)representation in the final film, was embedded in the dialogical process and pragmatic requirements of a collaborative film production, in which voice, autonomy and teacher authority were negotiated on a moment-by-moment basis. We conclude that it is vital for a reflexive practice and research to not gloss over the moral dilemmas in the name of progressive ideals, for example, when representations are co-created by project filmmakers/educators, but embrace these deliberations as part of the ‘fascinating collaborative matrix’ (Chambers 2019: 29) of participatory filmmaking

    Lrp Acts as Both a Positive and Negative Regulator for Type 1 Fimbriae Production in Salmonella enterica Serovar Typhimurium

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    Leucine-responsive regulatory protein (Lrp) is known to be an indirect activator of type 1 fimbriae synthesis in Salmonella enterica serovar Typhimurium via direct regulation of FimZ, a direct positive regulator for type 1 fimbriae production. Using RT-PCR, we have shown previously that fimA transcription is dramatically impaired in both lrp-deletion (Δlrp) and constitutive-lrp expression (lrpC) mutant strains. In this work, we used chromosomal PfimA-lacZ fusions and yeast agglutination assays to confirm and extend our previous results. Direct binding of Lrp to PfimA was shown by an electrophoretic mobility shift assay (EMSA) and DNA footprinting assay. Site-directed mutagenesis revealed that the Lrp-binding motifs in PfimA play a role in both activation and repression of type 1 fimbriae production. Overproduction of Lrp also abrogates fimZ expression. EMSA data showed that Lrp and FimZ proteins independently bind to PfimA without competitive exclusion. In addition, both Lrp and FimZ binding to PfimA caused a hyper retardation (supershift) of the DNA-protein complex compared to the shift when each protein was present alone. Nutrition-dependent cellular Lrp levels closely correlated with the amount of type 1 fimbriae production. These observations suggest that Lrp plays important roles in type 1 fimbriation by acting as both a positive and negative regulator and its effect depends, at least in part, on the cellular concentration of Lrp in response to the nutritional environment

    Elevated Incidence of Dental Caries in a Mouse Model of Cystic Fibrosis

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    Saliva bicarbonate constitutes the main buffering system which neutralizes the pH fall generated by the plaque bacteria during sugar metabolism. We found that the saliva pH is severely decreased in a mouse model of cystic fibrosis disease (CF). Given the close relationship between pH and caries development, we hypothesized that caries incidence might be elevated in the mouse CF model.). are enhanced at low pH values, we speculate that the decrease in the bicarbonate content and pH buffering of the saliva is at least partially responsible for the increased severity of lesions observed in the CF mouse

    Drinking in transition: trends in alcohol consumption in Russia 1994-2004

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    BACKGROUND: Heavy alcohol consumption is widespread in Russia, but studying changes in drinking during the transition from Communism has been hampered previously by the lack of frequent data. This paper uses 1-2 yearly panel data, comparing consumption trends with the rapid concurrent changes in economic variables (notably around the "Rouble crisis", shortly preceding the 1998 survey round), and mortality. METHODS: Data were from 9 rounds (1994-2004) of the 38-centre Russia Longitudinal Monitoring Survey. Respondents aged over 18 were included (>7,000 per round). Trends were measured in alcohol frequency, quantity per occasion (by beverage type) and 2 measures of potentially hazardous consumption: (i) frequent, heavy spirit drinking (≥80 g per occasion of vodka or samogon and >weekly) (ii) consuming samogon (cheap home-distilled spirit). Trends in consumption, mean household income and national mortality rates (in the same and subsequent 2 years) were compared. Finally, in a subsample of individual male respondents present in both the 1996 and 1998 rounds (before and after the financial crash), determinants of changes in harmful consumption were studied using logistic regression. RESULTS: Frequent, heavy spirit drinking (>80 g each time, ≥weekly) was widespread amongst men (12-17%) throughout, especially in the middle aged and less educated; with the exception of a significant, temporary drop to 10% in 1998. From 1996-2000, samogon drinking more than doubled, from 6% to 16% of males; despite a decline, levels were significantly higher in 2004 than 1996 in both sexes. Amongst women, frequent heavy spirit drinking rose non-significantly to more than 1% during the study. Heavy frequent male drinking and mortality in the same year were correlated in lower educated males, but not in women. Individual logistic regression in a male subsample showed that between 1996 and1998, those who lost their employment were more likely to cease frequent, heavy drinking; however, men who commenced drinking samogon in 1998 were more likely to be rural residents, materially poor, very heavy drinkers or pessimistic about their finances. These changes were unexplained by losses to follow-up. CONCLUSIONS: Sudden economic decline in late 1990s Russia was associated with a sharp, temporary fall in heavy drinking, and a gradual and persistent increase in home distilled spirit consumption, with the latter more common amongst disadvantaged groups. The correlation between heavy drinking and national mortality in lower educated men is interesting, but the timing of RLMS surveys late in the calendar year, and the absence of any correlation between drinking and the subsequent year's mortality, makes these data hard to interpret. Potential study limitations include difficulty in measuring multiple beverages consumed per occasion, and not specifically recording "surrogate" (non-beverage) alcohols

    Bacterial DNA topology and infectious disease

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    The Gram-negative bacterium Escherichia coli and its close relative Salmonella enterica have made important contributions historically to our understanding of how bacteria control DNA supercoiling and of how supercoiling influences gene expression and vice versa. Now they are contributing again by providing examples where changes in DNA supercoiling affect the expression of virulence traits that are important for infectious disease. Available examples encompass both the earliest stages of pathogen–host interactions and the more intimate relationships in which the bacteria invade and proliferate within host cells. A key insight concerns the link between the physiological state of the bacterium and the activity of DNA gyrase, with downstream effects on the expression of genes with promoters that sense changes in DNA supercoiling. Thus the expression of virulence traits by a pathogen can be interpreted partly as a response to its own changing physiology. Knowledge of the molecular connections between physiology, DNA topology and gene expression offers new opportunities to fight infection

    A Review of Dietary Prevention of Human Papillomavirus-Related Infection of the Cervix and Cervical Intraepithelial Neoplasia

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    The natural history of cervical cancer suggests that prevention can be achieved by modification of the host's immune system through a nutrient-mediated program. This study reviews the preventive role of dietary intake on cervical intraepithelial neoplasia (CIN) induced by human papillomavirus (HPV). Electronic databases were searched using relevant keywords such as, but not limited to, human papillomavirus infection, cervical intraepithelial neoplasia, lifestyle factors, nutrients intake, and diet. High consumption of fruit and vegetables appears to be protective against CIN. The findings also highlight the possibility of consuming high levels of specific nutrients, vitamins, and minerals, and retaining sufficient level of these elements in the body, especially those with high antioxidants and antiviral properties, to prevent progression of transient and persistent HPV infections to high-grade CIN 2 and 3 (including in situ cervical cancer). The protective effect is not significant for high-risk HPV persistent infections and invasive cervical cancer. Although it appears that intake of specific nutrients, vitamins, and minerals may be good in CIN prevention, there is lack of evidence from controlled trial to confirm this. Health professionals shall focus on implementation of a balanced-diet prevention strategy at an early stage for cervical cancer prevention

    Temperature Control of Fimbriation Circuit Switch in Uropathogenic Escherichia coli: Quantitative Analysis via Automated Model Abstraction

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    Uropathogenic Escherichia coli (UPEC) represent the predominant cause of urinary tract infections (UTIs). A key UPEC molecular virulence mechanism is type 1 fimbriae, whose expression is controlled by the orientation of an invertible chromosomal DNA element—the fim switch. Temperature has been shown to act as a major regulator of fim switching behavior and is overall an important indicator as well as functional feature of many urologic diseases, including UPEC host-pathogen interaction dynamics. Given this panoptic physiological role of temperature during UTI progression and notable empirical challenges to its direct in vivo studies, in silico modeling of corresponding biochemical and biophysical mechanisms essential to UPEC pathogenicity may significantly aid our understanding of the underlying disease processes. However, rigorous computational analysis of biological systems, such as fim switch temperature control circuit, has hereto presented a notoriously demanding problem due to both the substantial complexity of the gene regulatory networks involved as well as their often characteristically discrete and stochastic dynamics. To address these issues, we have developed an approach that enables automated multiscale abstraction of biological system descriptions based on reaction kinetics. Implemented as a computational tool, this method has allowed us to efficiently analyze the modular organization and behavior of the E. coli fimbriation switch circuit at different temperature settings, thus facilitating new insights into this mode of UPEC molecular virulence regulation. In particular, our results suggest that, with respect to its role in shutting down fimbriae expression, the primary function of FimB recombinase may be to effect a controlled down-regulation (rather than increase) of the ON-to-OFF fim switching rate via temperature-dependent suppression of competing dynamics mediated by recombinase FimE. Our computational analysis further implies that this down-regulation mechanism could be particularly significant inside the host environment, thus potentially contributing further understanding toward the development of novel therapeutic approaches to UPEC-caused UTIs

    Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP

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    Type 1 fimbriae are a crucial factor for the virulence of uropathogenic Escherichia coli during the first steps of infection by mediating adhesion to epithelial cells. They are also required for the consequent colonization of the tissues and for invasion of the uroepithelium. Here, we studied the role of the specialized signal transduction system CRP-cAMP in the regulation of type 1 fimbriation. Although initially discovered by regulating carbohydrate metabolism, the CRP-cAMP complex controls a major regulatory network in Gram-negative bacteria, including a broad subset of genes spread into different functional categories of the cell. Our results indicate that CRP-cAMP plays a dual role in type 1 fimbriation, affecting both the phase variation process and fimA promoter activity, with an overall repressive outcome on fimbriation. The dissection of the regulatory pathway let us conclude that CRP-cAMP negatively affects FimB-mediated recombination by an indirect mechanism that requires DNA gyrase activity. Moreover, the underlying studies revealed that CRP-cAMP controls the expression of another global regulator in Gram-negative bacteria, the leucine-responsive protein Lrp. CRP-cAMP-mediated repression is limiting the switch from the non-fimbriated to the fimbriated state. Consistently, a drop in the intracellular concentration of cAMP due to altered physiological conditions (e.g. growth in presence of glucose) increases the percentage of fimbriated cells in the bacterial population. We also provide evidence that the repression of type 1 fimbriae by CRP-cAMP occurs during fast growth conditions (logarithmic phase) and is alleviated during slow growth (stationary phase), which is consistent with an involvement of type 1 fimbriae in the adaptation to stress conditions by promoting biofilm growth or entry into host cells. Our work suggests that the metabolic sensor CRP-cAMP plays a role in coupling the expression of type 1 fimbriae to environmental conditions, thereby also affecting subsequent attachment and colonization of host tissues
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