496 resultados para virulence factors


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Enterohaemorrhagic Escherichia coli (EHEC) are a subgroup of Shiga toxin-producing E. coli that cause gastrointestinal disease with the potential for life-threatening sequelae. Cattle serve as the natural reservoir for EHEC and outbreaks occur sporadically as a result of contaminated beef and other farming products. While certain EHEC virulence mechanisms have been extensively studied, the factors that mediate host colonization are poorly defined. Previously, we identified four proteins (EhaA,B,C,D) from the prototypic EHEC strain EDL933 that belong to the autotransporter (AT) family. Here we characterize the EhaB AT protein. EhaB was shown to be located at the cell surface and overexpression in E. coli K-12 resulted in significant biofilm formation under continuous flow conditions. Overexpression of EhaB in E. coli K12 and EDL933 backgrounds also promoted adhesion to the extracellular matrix proteins collagen I and laminin. An EhaB-specific antibody revealed that EhaB is expressed in E. coli EDL933 following in vitro growth. EhaB also cross-reacted with serum IgA from cattle challenged with E. coli O157:H7, indicating that EhaB is expressed in vivo and elicits a host IgA immune response.

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Disulfide bond (DSB) formation is catalyzed by disulfide bond proteins and is critical for the proper folding and functioning of secreted and membrane-associated bacterial proteins. Uropathogenic Escherichia coli (UPEC) strains possess two paralogous disulfide bond systems: the well-characterized DsbAB system and the recently described DsbLI system. In the DsbAB system, the highly oxidizing DsbA protein introduces disulfide bonds into unfolded polypeptides by donating its redox-active disulfide and is in turn reoxidized by DsbB. DsbA has broad substrate specificity and reacts readily with reduced unfolded proteins entering the periplasm. The DsbLI system also comprises a functional redox pair; however, DsbL catalyzes the specific oxidative folding of the large periplasmic enzyme arylsulfate sulfotransferase (ASST). In this study, we characterized the DsbLI system of the prototypic UPEC strain CFT073 and examined the contributions of the DsbAB and DsbLI systems to the production of functional flagella as well as type 1 and P fimbriae. The DsbLI system was able to catalyze disulfide bond formation in several well-defined DsbA targets when provided in trans on a multicopy plasmid. In a mouse urinary tract infection model, the isogenic dsbAB deletion mutant of CFT073 was severely attenuated, while deletion of dsbLI or assT did not affect colonization.

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In general, the biological activation of nephrocarcinogenic chlorinated hydrocarbons proceeds via conjugatiton with glutathione. It has mostly been assamed that the main site of initial conjugation is the liver, followed by a mandatory transfer of intermediates to the kidney. It was therefore of interest to study the enzyme activities of subgroups of glutathione transferases (GSTs) in renal cancers and the surrounding normal renal tissues of the same individuals (n = 21). For genotyping the individuals with respect to known polymorphic GST isozymes the following substrates with differential specificity were used: 1-chloro-2,4-dinitrobenzene for overall GST activity (except GST θ); 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole for GST α; 1,2-dichloro-4-nitro-benzene for GST μ; ethacrynic acid and 4-vinylpyridine for GST π; and methyl chloride for GST θ. In general, the normal tissues were able to metabolize the test substrates. A general decrease in individual GST enzyme activities was apparent in the course of cancerization, and in some (exceptional) cases individual activities, expressed in the normal renal tissue, were lost in the tumour tissue. The GST enzyme activities in tumours were independent of tumour stage, or the age and gender of the patients. There was little influence of known polymorphisms of GSTM1, GSTM3 and GSTP1 upon the activities towards the test substrates, whereas the influence of GSTT1 polymorphism on the activity towads methyl chloride was straightforward. In general, the present findings support the concept that the initial GST-dependent bioactivation step of nephrocarcinogenic chlorinated hydrocarbons may take place in the kidney itself. This should be a consideration in toxicokinetic modelling.

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Purpose: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e.g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1-2 carbon atoms) were investigated. Material and Methods: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. Results: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6%) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8%) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). Conclusions: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis. [Article in German]

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Epithelial to mesenchymal transition (EMT) has gained widespread acceptance over recent years as a mechanism by which normally sessile epithelial tumour cells can move away from the primary tumour and metastasize. This review article examines the role of a number of growth factors in inducing EMT, and the reverse process mesenchymal to epithelial transition. Unique and common intracellular signalling pathways are highlighted. A comprehensive understanding of the regulation of EMT will be critical in manipulating this process to develop novel anti-metastasis therapies.

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BACKGROUND: Within Australia and internationally (Health Workforce Australia, 2012) an increasing and on-going nursing workforce shortage is documented. Recent international estimates indicate that there will be ongoing and significant gaps in the supply of a nursing workforce; the United Kingdom is predicted to have a reduction of 12.12% nurses over the coming eight years if a current 'steady state' is maintained (Buchan and Seacombe, 2011); Canada is predicted to have a shortage of 60,000 nurses by 2022 (Tomblin et al., 2012) with Australia's anticipated nursing shortage reported as over 90,000 by the year 2025 (Health Workforce Australia, 2012). Queensland Health in response to their tracked emerging nursing and midwifery workforce shortages developed a nursing and midwifery refresher programme to return registered staff back to the workforce. A study was undertaken between 2008 and 2010 to provide an understanding of how non-practising nurses and midwives maybe supported back into the workforce. METHODS: Programme applicants (444) were invited to respond to an on-line survey designed to understand what aspects of the programme supported their learning and ability to return to the workforce. This number represents those who applied but not all completed or commenced the programme. Descriptive statistics (Polit and Beck, 2008) were used to collate quantifiable survey responses and free text and unsolicited responses were themed. RESULTS: The survey received a 35.5% response rate (n=158) with a return of 20% of unsolicited comments in the form of e-mail responses which were included in the themed results. Key themes supporting participants' learning and ability to return to the workforce were: Respondents were 94% female and 6% male, with 37.7% >51 years of age. Child rearing was the foremost reason for female staff relinquishing workforce roles (36.6%). The primary reason for returning to the workforce was maintenance of registration (40.5%). Both theory and clinical placement components were seen by participants as contributing to their confidence to return to the health workforce. CONCLUSION: The Queensland Nursing and Midwifery Refresher Programs provided a structured programme for registered, non-practising nurses and midwives to return to the Queensland Health workforce. Responses indicated that clinical supervision and contract learning should be central to a return to workforce induction programme for registered but non-practising nurses and midwives. The majority of nurses and midwives returning to the workforce were approaching retirement age in 10-15 years.

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Purpose To determine the prevalence of falls in the 12 months prior to cataract surgery and examine the associations between visual and other risk factors and falls among older bilateral cataract patients in Vietnam. Methods Data collected from 413 patients in the week before scheduled cataract surgery included a questionnaire and three objective visual tests. Results The outcome of interest was self-reported falls in the previous 12 months. A total of 13% (n = 53) of bilateral cataract patients reported 60 falls within the previous 12 months. After adjusting for age, sex, race, employment status, comorbidities, medication usage, refractive management, living status and the three objective visual tests in the worse eye, women (odds ratio, OR, 4.64, 95% confidence interval, CI, 1.85–11.66), and those who lived alone (OR 4.51, 95% CI 1.44–14.14) were at increased risk of a fall. Those who reported a comorbidity were at decreased risk of a fall (OR 0.43, 95% CI 0.19–0.95). Contrast sensitivity (OR 0.31, 95% CI 0.10–0.95) was the only significant visual test associated with a fall. These results were similar for the better eye, except the presence of a comorbidity was not significant (OR 0.45, 95% CI 0.20–1.02). Again, contrast sensitivity was the only significant visual factor associated with a fall (OR 0.15, 95% CI 0.04–0.53). Conclusion Bilateral cataract patients in Vietnam are potentially at high risk of falls and in need of falls prevention interventions. It may also be important for ophthalmologists and health professionals to consider contrast sensitivity measures when prioritizing cataract patients for surgery and assessing their risk of falls.

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Over the past decades there has been a considerable development in the modeling of car-following (CF) behavior as a result of research undertaken by both traffic engineers and traffic psychologists. While traffic engineers seek to understand the behavior of a traffic stream, traffic psychologists seek to describe the human abilities and errors involved in the driving process. This paper provides a comprehensive review of these two research streams. It is necessary to consider human-factors in {CF} modeling for a more realistic representation of {CF} behavior in complex driving situations (for example, in traffic breakdowns, crash-prone situations, and adverse weather conditions) to improve traffic safety and to better understand widely-reported puzzling traffic flow phenomena, such as capacity drop, stop-and-go oscillations, and traffic hysteresis. While there are some excellent reviews of {CF} models available in the literature, none of these specifically focuses on the human factors in these models. This paper addresses this gap by reviewing the available literature with a specific focus on the latest advances in car-following models from both the engineering and human behavior points of view. In so doing, it analyses the benefits and limitations of various models and highlights future research needs in the area.

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Introduction: Built environment interventions designed to reduce non-communicable diseases and health inequity, complement urban planning agendas focused on creating more ‘liveable’, compact, pedestrian-friendly, less automobile dependent and more socially inclusive cities.However, what constitutes a ‘liveable’ community is not well defined. Moreover, there appears to be a gap between the concept and delivery of ‘liveable’ communities. The recently funded NHMRC Centre of Research Excellence (CRE) in Healthy Liveable Communities established in early 2014, has defined ‘liveability’ from a social determinants of health perspective. Using purpose-designed multilevel longitudinal data sets, it addresses five themes that address key evidence-base gaps for building healthy and liveable communities. The CRE in Healthy Liveable Communities seeks to generate and exchange new knowledge about: 1) measurement of policy-relevant built environment features associated with leading non-communicable disease risk factors (physical activity, obesity) and health outcomes (cardiovascular disease, diabetes) and mental health; 2) causal relationships and thresholds for built environment interventions using data from longitudinal studies and natural experiments; 3) thresholds for built environment interventions; 4) economic benefits of built environment interventions designed to influence health and wellbeing outcomes; and 5) factors, tools, and interventions that facilitate the translation of research into policy and practice. This evidence is critical to inform future policy and practice in health, land use, and transport planning. Moreover, to ensure policy-relevance and facilitate research translation, the CRE in Healthy Liveable Communities builds upon ongoing, and has established new, multi-sector collaborations with national and state policy-makers and practitioners. The symposium will commence with a brief introduction to embed the research within an Australian health and urban planning context, as well as providing an overall outline of the CRE in Healthy Liveable Communities, its structure and team. Next, an overview of the five research themes will be presented. Following these presentations, the Discussant will consider the implications of the research and opportunities for translation and knowledge exchange. Theme 2 will establish whether and to what extent the neighbourhood environment (built and social) is causally related to physical and mental health and associated behaviours and risk factors. In particular, research conducted as part of this theme will use data from large-scale, longitudinal-multilevel studies (HABITAT, RESIDE, AusDiab) to examine relationships that meet causality criteria via statistical methods such as longitudinal mixed-effect and fixed-effect models, multilevel and structural equation models; analyse data on residential preferences to investigate confounding due to neighbourhood self-selection and to use measurement and analysis tools such as propensity score matching and ‘within-person’ change modelling to address confounding; analyse data about individual-level factors that might confound, mediate or modify relationships between the neighbourhood environment and health and well-being (e.g., psychosocial factors, knowledge, perceptions, attitudes, functional status), and; analyse data on both objective neighbourhood characteristics and residents’ perceptions of these objective features to more accurately assess the relative contribution of objective and perceptual factors to outcomes such as health and well-being, physical activity, active transport, obesity, and sedentary behaviour. At the completion of the Theme 2, we will have demonstrated and applied statistical methods appropriate for determining causality and generated evidence about causal relationships between the neighbourhood environment, health, and related outcomes. This will provide planners and policy makers with a more robust (valid and reliable) basis on which to design healthy communities.

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This article considers the increased identification of special educational needs in Australia’s largest education system from the perspectives of senior public servants, regional directors, principals, school counsellors, classroom teachers, support class teachers, learning support teachers and teaching assistants (n = 30). While their perceptions of an increase generally align with the story told by official statistics, participants’ narratives reveal that school-based identification of special educational needs is neither art nor science. This research finds that rather than an objective indication of the number and nature of children with SEN, official statistics may be more appropriately viewed as a product of funding eligibility and the assumptions of the adults who teach, refer and assess children who experience difficulties in school and with learning.

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While existing multi-biometic Dempster-Shafer the- ory fusion approaches have demonstrated promising perfor- mance, they do not model the uncertainty appropriately, sug- gesting that further improvement can be achieved. This research seeks to develop a unified framework for multimodal biometric fusion to take advantage of the uncertainty concept of Dempster- Shafer theory, improving the performance of multi-biometric authentication systems. Modeling uncertainty as a function of uncertainty factors affecting the recognition performance of the biometric systems helps to address the uncertainty of the data and the confidence of the fusion outcome. A weighted combination of quality measures and classifiers performance (Equal Error Rate) are proposed to encode the uncertainty concept to improve the fusion. We also found that quality measures contribute unequally to the recognition performance, thus selecting only significant factors and fusing them with a Dempster-Shafer approach to generate an overall quality score play an important role in the success of uncertainty modeling. The proposed approach achieved a competitive performance (approximate 1% EER) in comparison with other Dempster-Shafer based approaches and other conventional fusion approaches.

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Legislation giving prominence to psychosocial risk factors at work has changed the role of government occupational health and safety (OHS) inspectors in many countries. Yet little is known about how inspectorates have responded to these changes. Between 2003 and 2007 an Australian study was undertaken on OHS standards, entailing detailed documentary analysis, interviews with 36 inspectorate managers and 89 inspectors, and observations made when researchers accompanied inspectors on 120 typical workplace visits. Our study found that general duty provisions in OHS legislation clearly incorporated psychosocial hazards and inspectorates had introduced guidance material, pursued campaigns and increased interventions in this area. However, the regulatory framework remained narrow (focused on bullying/harassment, occupational violence and work stress) and workplace visits revealed psychosocial hazards as a marginal area of inspectorate activity. These findings were reinforced in interviews. While aware of psychosocial hazards inspectors often saw the issue as problematic due to limited training, resourcing constraints, deficiencies in regulation and fears of victimisation amongst workers. In order to address these problems a number of changes are required that recognize the distinctiveness of psychosocial hazards including their ‘invisibility’. Notable here are revisions to regulation (both general duty provisions and specific codes), the development of comprehensive guidance and assessment tools to be used by inspectors, greater use of procedural enforcement, and enhanced inspectorate resourcing and training. There is also a need to recognize complex inter-linkages between psychosocial hazards and the industrial relations context.

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This paper demonstrates a renewed procedure for the quantification of surface-enhanced Raman scattering (SERS) enhancement factors with improved precision. The principle of this method relies on deducting the resonance Raman scattering (RRS) contribution from surface-enhanced resonance Raman scattering (SERRS) to end up with the surface enhancement (SERS) effect alone. We employed 1,8,15,22-tetraaminophthalocyanato-cobalt(II) (4α-CoIITAPc), a resonance Raman- and electrochemically redox-active chromophore, as a probe molecule for RRS and SERRS experiments. The number of 4α-CoIITAPc molecules contributing to RRS and SERRS phenomena on plasmon inactive glassy carbon (GC) and plasmon active GC/Au surfaces, respectively, has been precisely estimated by cyclic voltammetry experiments. Furthermore, the SERS substrate enhancement factor (SSEF) quantified by our approach is compared with the traditionally employed methods. We also demonstrate that the present approach of SSEF quantification can be applied for any kind of different SERS substrates by choosing an appropriate laser line and probe molecule.

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Social marketers and governments have often targeted hard to reach or vulnerable groups (Gordon et al., 2006) such as young adults and low income earners. Past research has shown that low-income earners are often at risk of poor health outcomes and diminished lifestyle (Hampson et al., 2009; Scott et al., 2012). Young adults (aged 18 to 35) are in a transition phase of their life where lifestyle preferences are still being formed and are thus a useful target for long-term sustainable change. An area of focus for all levels of government is the use of energy with an aim to reduce consumption. There is little research to date that combines both of these groups and in particular in the context of household energy usage. Research into financially disadvantaged consumers is challenging the notion that that low income consumer purchasing and usage of products and services is based upon economic status (Sharma et al., 2012). Prior research shows higher income earners view items such as televisions and computers as necessities rather than non-essential (Karlsson et al., 2004). Consistent with this is growing evidence that low income earners purchase non-essential, energy intensive electronic appliances such as multiple big screen TV sets and additional refrigerators. With this in mind, there is a need for knowledge about how psychological and economic factors influence the energy consumption habits (e.g. appliances on standby power, leaving appliances turned on, running multiple devices at one time) of low income earners. Thus, our study sought to address the research question of: What are the factors that influence young adult low-income earners energy habits?

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This thesis examines how psychosocial factors influence the report of persistent symptoms after mild traumatic brain injury. Using quasi-experimental methods, the research program demonstrates how factors unrelated to trauma-induced physiological brain damage can contribute to persistent symptoms after a mild traumatic brain injury. The results of this thesis highlight the possibility that outcome from mild traumatic brain injury could be improved by targeting psychosocial factors.