Functional heterogeneity of the UpaH autotransporter protein from Uropathogenic Escherichia coli

Uropathogenic Escherichia coli (UPEC) is responsible for the majority of urinary tract infections (UTI). To cause a UTI, UPEC must adhere to the epithelial cells of the urinary tract and overcome the shear flow forces of urine. This function is mediated primarily by fimbrial adhesins, which mediate specific attachment to host cell receptors. Another group of adhesins that contributes to UPEC-mediated UTI is autotransporter (AT) proteins. AT proteins possess a range of virulence properties, such as adherence, aggregation, invasion, and biofilm formation. One recently characterized AT protein of UPEC is UpaH, a large adhesin-involved-in-diffuse-adherence (AIDA-I)-type AT protein that contributes to biofilm formation and bladder colonization. In this study we characterized a series of naturally occurring variants of UpaH. We demonstrate that extensive sequence variation exists within the passenger-encoding domain of UpaH variants from different UPEC strains. This sequence variation is associated with functional heterogeneity with respect to the ability of UpaH to mediate biofilm formation. In contrast, all of the UpaH variants examined retained a conserved ability to mediate binding to extracellular matrix (ECM) proteins. Bioinformatic analysis of the UpaH passenger domain identified a conserved region (UpaHCR) and a hydrophobic region (UpaHHR). Deletion of these domains reduced biofilm formation but not the binding to ECM proteins. Despite variation in the upaH sequence, the transcription of upaH was repressed by a conserved mechanism involving the global regulator H-NS, and mutation of the hns gene relieved this repression. Overall, our findings shed new light on the regulation and functions of the UpaH AT protein.

Common hazards and their mitigating measures in work zones : a qualitative study of worker perceptions

Road construction and maintenance activities present challenges for ensuring the safety of workers and the traveling public alike. Hazards in work zones are typically studied using historical crash records but the current study took a qualitative approach by interviewing 66 workers from various work zones in Queensland, Australia. This supplemented and enhanced the limited available data regarding the frequency and nature of work zone crashes in Australia, provided worker insights into contributing factors, and assessed their opinions on the likely effectiveness of current or future approaches to hazard mitigation. Workers may not be aware of objective data regarding effectiveness, but their attitudes and consequent levels of compliance can influence both the likelihood of implementation and the outcomes of safety measures. Despite the potential importance of worker perceptions, they have not been studied comprehensively to date, and thus this study fills a significant gap in the literature. Excessive vehicle speeds, driver distraction and aggression towards roadworkers, working in wet weather, at night and close to traffic stream were among the most common hazards noted by workers. The safety measures perceived to be most effective included police presence, active enforcement, and improving driver awareness and education about work zones. Worker perceptions differed according to their level of exposure to hazards.

Dismantling worker categories: the primary duty of care, and worker consultation, participation and representation, in the model Work Health and Safety Bill 2009

Late in 2009, the Australian Workplace Relations Ministers' Council endorsed the model Work Health and Safety Bill 2009, which is to be adopted by all Australian governments (federal, state and territory) from 01 January 2012. This paper describes and analyses two key sets of provisions in this model legislation. The first establishes a 'primary' duty of care imposed not on 'employers' but on persons conducting a business or undertaking, and owed to all kinds of workers engaged, directed or influenced by the person conducting the business or undertaking. The second encompasses broad duties on all persons conducting a business or undertaking to consult with workers who carry out work for the business or undertaking and who are directly affected by a work health and safety issue, and to facilitate the election of health and safety representatives representing all workers who carry out work for the business or undertaking. These provisions arguably make a significant contribution to solving a problem faced by occupational safety and health regulators around the world – modifying regulation to accommodate all forms of precarious work.

The implications of de‐collectivist industrial relations laws and associated developments for worker health and safety in Australia, 1996–2007

The institutional and regulatory interlinkages between industrial relations (IR) and occupational health and safety (OHS) are seldom explored in the IR literature. This article begins to address this gap by examining regulatory initiatives in Australia during a period of neoliberal government. It examines the laws enacted by the federal government during this period and events and cases arising from these laws that go some way to illustrating their effects. Evidence is also drawn from detailed research on a number of state OHS inspectorates between 2004 and 2006. It is argued that de-collectivist changes to IR laws exacerbated problems posed by the growth of flexible work arrangements and a drop in union density, weakening participatory provisions in OHS laws and promoting work arrangements that undermined OHS standards. The study provides evidence of the implications of a divergence in the trajectory of IR and OHS laws and the importance of better integrating worker protection laws.

Work zone items influencing driver speeds at roadworks: worker, driver and expert perspectives

Roadworks are essential to a safe and efficient road network, yet somewhat paradoxically the necessary work is often associated with increased risk to motorists and workers, as well as with traffic flow disruptions. A major source of increased crash risk at roadwork sites (work zones) is poor speed limit compliance. Speeding in work zones is examined in existing literature to the extent that major issues are known and some effective countermeasures are identified. However, as speeding remains a major problem in work zones, influences on driver behaviour arguably need to be better understood to achieve greater compliance and thus realise further gains in road safety. Current research on safety at Queensland roadwork sites has examined the views of workers, measured work zone speed profiles, and conducted an online survey of drivers (N=410). This paper focuses on survey participants’ ratings of 12 specific work zone items (including traffic control measures) in terms of their influence on speed choice. Repeated measures ANOVA revealed statistically significant differences (p<0.001) in the ratings of these items, with the most influential including visible presence of workers, visible police presence, and speed feedback displays. Those rated least influential included ’roadwork speed limits are enforced’ and ‘reduce speed’ signs and increased fines for speeding in work zones. The paper considers the alignment of these findings with those from other sources, including worker interviews and the literature, to provide a consolidated assessment of the influence of work zone items on driver speeds.

Beyond the dotted drawings : the Aboriginal Health Worker and health promotion practice

Aboriginal and Torres Strait Islander health workers' roles have changed over the years as the profession has shifted far beyond the mere provision of a cultural brokerage service. Important achievements have been made in enhancing the biomedical role of the Aboriginal and Torres Strait health worker, even though this is not the only area of expertise they need to possess.

Mitochondrial DNA sequence analysis from multiple gene fragments reveals genetic heterogeneity of Crassostrea ariakensis in East Asia

The native Asian oyster, Crassostrea ariakensis is one of the most common and important Crassostrea species that occur naturally along the coast of East Asia. Molecular species diagnosis is a prerequisite for population genetic analysis of wild oyster populations because oyster species cannot be discriminated reliably using external morphological characters alone due to character ambiguity. To date there have been few phylogeographic studies of natural edible oyster populations in East Asia, in particular this is true of the common species in Korea C. ariakensis. We therefore assessed the levels and patterns of molecular genetic variation in East Asian wild populations of C. ariakensis from Korea, Japan, and China using DNA sequence analysis of five concatenated mtDNA regions namely; 16S rRNA, cytochrome oxidase I, cytochrome oxidase II, cytochrome oxidase III, and cytochrome b. Two divergent C. ariakensis clades were identified between southern China and remaining sites from the northern region. In addition, hierarchical AMOVA and pairwise UST analyses showed that genetic diversity was discontinuous among wild populations of C. ariakensis in East Asia. Biogeographical and historical sea level changes are discussed as potential factors that may have influenced the genetic heterogeneity of wild C. ariakensis stocks across this region.

Fractional diffusion models of cardiac electrical propagation: Role of structural heterogeneity in dispersion of repolarization

Impulse propagation in biological tissues is known to be modulated by structural heterogeneity. In cardiac muscle, improved understanding on how this heterogeneity influences electrical spread is key to advancing our interpretation of dispersion of repolarization. We propose fractional diffusion models as a novel mathematical description of structurally heterogeneous excitable media, as a means of representing the modulation of the total electric field by the secondary electrical sources associated with tissue inhomogeneities. Our results, analysed against in vivo human recordings and experimental data of different animal species, indicate that structural heterogeneity underlies relevant characteristics of cardiac electrical propagation at tissue level. These include conduction effects on action potential (AP) morphology, the shortening of AP duration along the activation pathway and the progressive modulation by premature beats of spatial patterns of dispersion of repolarization. The proposed approach may also have important implications in other research fields involving excitable complex media.

Mixture models of nucleotide sequence evolution that account for heterogeneity in the substitution process across sites and across lineages

Molecular phylogenetic studies of homologous sequences of nucleotides often assume that the underlying evolutionary process was globally stationary, reversible, and homogeneous (SRH), and that a model of evolution with one or more site-specific and time-reversible rate matrices (e.g., the GTR rate matrix) is enough to accurately model the evolution of data over the whole tree. However, an increasing body of data suggests that evolution under these conditions is an exception, rather than the norm. To address this issue, several non-SRH models of molecular evolution have been proposed, but they either ignore heterogeneity in the substitution process across sites (HAS) or assume it can be modeled accurately using the distribution. As an alternative to these models of evolution, we introduce a family of mixture models that approximate HAS without the assumption of an underlying predefined statistical distribution. This family of mixture models is combined with non-SRH models of evolution that account for heterogeneity in the substitution process across lineages (HAL). We also present two algorithms for searching model space and identifying an optimal model of evolution that is less likely to over- or underparameterize the data. The performance of the two new algorithms was evaluated using alignments of nucleotides with 10 000 sites simulated under complex non-SRH conditions on a 25-tipped tree. The algorithms were found to be very successful, identifying the correct HAL model with a 75% success rate (the average success rate for assigning rate matrices to the tree's 48 edges was 99.25%) and, for the correct HAL model, identifying the correct HAS model with a 98% success rate. Finally, parameter estimates obtained under the correct HAL-HAS model were found to be accurate and precise. The merits of our new algorithms were illustrated with an analysis of 42 337 second codon sites extracted from a concatenation of 106 alignments of orthologous genes encoded by the nuclear genomes of Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, S. castellii, S. kluyveri, S. bayanus, and Candida albicans. Our results show that second codon sites in the ancestral genome of these species contained 49.1% invariable sites, 39.6% variable sites belonging to one rate category (V1), and 11.3% variable sites belonging to a second rate category (V2). The ancestral nucleotide content was found to differ markedly across these three sets of sites, and the evolutionary processes operating at the variable sites were found to be non-SRH and best modeled by a combination of eight edge-specific rate matrices (four for V1 and four for V2). The number of substitutions per site at the variable sites also differed markedly, with sites belonging to V1 evolving slower than those belonging to V2 along the lineages separating the seven species of Saccharomyces. Finally, sites belonging to V1 appeared to have ceased evolving along the lineages separating S. cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus, implying that they might have become so selectively constrained that they could be considered invariable sites in these species.

Creating heterogeneity: Evolving use of groupware in a network of freelancers

This contribution is a long-term study of the evolving use of the organization-wide groupware in a service network. We are describing the practices related to organization-wide groupware in conjunction with local groupware-related practices and how they have proceeded since the organization was established. In the discussion of these practices we are focussing on issues such as: 1. tendencies for proliferation and integration, 2. local appropriations of a variety of systems, 3. creative appropriations, including the creation of a unique heterogeneous groupware fabric, 4. the design strategy of multiple parallel experimental use an; 5. the relation between disparate local meanings and successful computer supported cooperative practice. As an overarching theme we are exploring the explanatory value of the concepts of objectification and appropriation as compared to the concepts of design vs. use.

Heterogeneity of miR-10b expression in circulating tumor cells

Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as € liquid biopsyto aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch ® CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients.

Worker views on safety at roadworks

Roadworks in live traffic environments are hazardous to workers and road users alike. In an increasing body of international research literature, roadwork risks and hazards have been comprehensively examined. As in the broader field of road safety research, much of the work rightly takes a quantitative approach to assessing risk and related issues and to addressing the identified risks appropriately. In Australia, however, limited official data constrains the ability of researchers to achieve an in-depth understanding of the situation at state/territory and national levels based on traditional quantitative analyses. One way to enhance and supplement the limited available data is to consult those who are directly involved in roadworks for qualitative information, although such an approach is rarely reported in the roadwork safety arena. As part of the major study focusing on safety at roadworks in Queensland, 66 workers were interviewed about their perceptions and experiences regarding roadwork safety. This paper thus outlines a qualitative examination of workers' perceptions of the causes of roadwork incidents and the effectiveness of hazard mitigation measures. Consistent with findings reported in the literature is the view among workers that speeding is a major hazard and that police enforcement is the most effective countermeasure. Other hazards commonly observed by workers but less frequently reported elsewhere include driver distraction and aggression toward workers, working in poor weather and working at night. Workers mostly suggested educational measures to address distraction and aggression issues, though such measures are only tentatively supported in the literature.