Role of capsule and O antigen in the virulence of uropathogenic Escherichia coli

Urinary tract infection (UTI) is one of the most common bacterial infections in humans, with uropathogenic Escherichia coli (UPEC) the leading causative organism. UPEC has a number of virulence factors that enable it to overcome host defenses within the urinary tract and establish infection. The O antigen and the capsular polysaccharide are two such factors that provide a survival advantage to UPEC. Here we describe the application of the rpsL counter selection system to construct capsule (kpsD) and O antigen (waaL) mutants and complemented derivatives of three reference UPEC strains: CFT073 (O6:K2:H1), RS218 (O18:K1:H7) and 1177 (O1:K1:H7). We observed that while the O1, O6 and O18 antigens were required for survival in human serum, the role of the capsule was less clear and linked to O antigen type. In contrast, both the K1 and K2 capsular antigens provided a survival advantage to UPEC in whole blood. In the mouse urinary tract, mutation of the O6 antigen significantly attenuated CFT073 bladder colonization. Overall, this study contrasts the role of capsule and O antigen in three common UPEC serotypes using defined mutant and complemented strains. The combined mutagenesis-complementation strategy can be applied to study other virulence factors with complex functions both in vitro and in vivo.

Specialist nursing training in Poland: Applications for neuroscience nursing

Background: Nurses have a pivotal role in providing, facilitating, advocating and promoting the best possible care and outcome for the client. To ensure decisions and actions are based on current standards of practice, nurses must be accountable for participation in ongoing education in their area of practice. Aim: To present a description of the current state of Polish nursing education and specialized model for neurological and neurosurgical nursing that can be utilized for both undergraduate and postgraduate continuing education in Poland. Data sources: The model of postgraduate training introduced in Poland in 2000 was taken into consideration in developing the framework for neuroscience nursing postgraduate continuing education presented here. The framework for neurological continuing education is also based on a review of the literature and is consistent with Poland’s legally binding professional nursing regulations (normative and implementing regulations). Conclusion: The model demonstrates the need for the content of pre- and post-undergraduate degree education in neurological nursing to be graduated, based on the frameworks for undergraduate education (acquiring the knowledge and basic skills for performing the work of nurses) and postgraduate education (acquiring knowledge and specialist skills necessary for providing advanced nursing care including medical acts on patients with nervous system diseases). Implications for nursing: New and advanced skills gained in specialization training can be applied to complex functions, roles and professional tasks undertaken by nurses in relation to care of patients with neurological dysfunctions.

A generative design system based on evolutionary and mathematical functions

Previous work by Professor John Frazer on Evolutionary Architecture provides a basis for the development of a system evolving architectural envelopes in a generic and abstract manner. Recent research by the authors has focused on the implementation of a virtual environment for the automatic generation and exploration of complex forms and architectural envelopes based on solid modelling techniques and the integration of evolutionary algorithms, enhanced computational and mathematical models. Abstract data types are introduced for genotypes in a genetic algorithm order to develop complex models using generative and evolutionary computing techniques. Multi-objective optimisation techniques are employed for defining the fitness function in the evaluation process.

Organisational challenges in understanding and implementing effective buiness continuity management strategies in a complex and critical organisation : an airport case study

With the increasing complexity of modern day threats and the growing sophistication of interlinked and interdependent operating environments, Business Continuity Management (BCM) has emerged as a new discipline, offering a strategic approach to safeguarding organisational functions. Of significant interest is the application of BCM frameworks and strategies within critical infrastructure, and in particular the aviation industry. Given the increased focus on security and safety for critical infrastructures, research into the adoption of BCM principles within an airport environment provides valuable management outcomes and research into a previously neglected area of inquisition. This research has used a single case study methodology to identify possible impediments to BCM adoption and implementation by the Brisbane Airport Corporation (BAC). It has identified a number of misalignments between the required breadth of focus for a BCM program, identified differing views on specific roles and responsibilities required during a major disruptive event and illustrated the complexities of the Brisbane Airport which impede the understanding and implementation of effective Business Continuity Management Strategies.

The effects of cognitive ageing on the use of complex interfaces

This paper discusses an experiment investigating the effects of cognitive ageing and prior-experience with technology on using complex interfaces intuitively. Overall 37 participants, between the ages of 18 to 83, participated in this study. All participants were assessed for their cognitive abilities and prior-experience with technology. It was anticipated that the Central Executive function (a component of Working Memory) would emerge as one of the important cognitive functions in using complex interfaces. This was found to be the case with the strongest negative correlation occurring between sustained attention (one of the functions of the Central Executive), the time to complete the task and number of errors made by the participants.

Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex

hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).

Ageing and use of complex product interfaces

This paper presents an experiment designed to investigate if redundancy in an interface has any impact on the use of complex interfaces by older people and people with low prior-experience with technology. The important findings of this study were that older people (65+ years) completed the tasks on the Words only based interface faster than on Redundant (text and symbols) interface. The rest of the participants completed tasks significantly faster on the Redundant interface. From a cognitive processing perspective, sustained attention (one of the functions of Central Executive) has emerged as one of the important factors in completing tasks on complex interfaces faster and with fewer of errors.

Integration-segregation decisions under general value functions: "create your own bundle - choose 1, 2, or all 3!",

Whether to keep products segregated (e.g., unbundled) or integrate some or all of them (e.g., bundle) has been a problem of profound interest in areas such as portfolio theory in finance, risk capital allocations in insurance and marketing of consumer products. Such decisions are inherently complex and depend on factors such as the underlying product values and consumer preferences, the latter being frequently described using value functions, also known as utility functions in economics. In this paper, we develop decision rules for multiple products, which we generally call ‘exposure units’ to naturally cover manifold scenarios spanning well beyond ‘products’. Our findings show, e.g. that the celebrated Thaler's principles of mental accounting hold as originally postulated when the values of all exposure units are positive (i.e. all are gains) or all negative (i.e. all are losses). In the case of exposure units with mixed-sign values, decision rules are much more complex and rely on cataloging the Bell number of cases that grow very fast depending on the number of exposure units. Consequently, in the present paper, we provide detailed rules for the integration and segregation decisions in the case up to three exposure units, and partial rules for the arbitrary number of units.

On the beach : exploring the complex egalitarianism of the Australian beach

Australia, internationally, is known as a beach loving country, particularly in popular culture. The beach did not figure significantly in academic discussion before the 1980s when Fiske, Hodge, and Turner (1987, 54) researched the beach as a space of myth, seeing it as an integral part of the modern Australian identity. One common myth in Australia is that the beach is an equaliser, a place of multiple ethnicities, shapes, sizes, and genders (Dutton, 1985). I agree that the beach remains a significant aspect of Australian identity; however, limiting its meaning to a mythic space contributing to a homogenous national identity is not adequate. This paper will explore how Australian texts comment on or challenge the myth of the beach as an egalitarian space. I argue that recent Australian texts show a more complex, layered representation of this concept; and that the beach also in this respect can no longer be understood as a myth transcending difference.

Identifying Core Functions of Asset Management

It is widely acknowledged that effective asset management requires an interdisciplinary approach, in which synergies should exist between traditional disciplines such as: accounting, engineering, finance, humanities, logistics, and information systems technologies. Asset management is also an important, yet complex business practice. Business process modelling is proposed as an approach to manage the complexity of asset management through the modelling of asset management processes. A sound foundation for the systematic application and analysis of business process modelling in asset management is, however, yet to be developed. Fundamentally, a business process consists of activities (termed functions), events/states, and control flow logic. As both events/states and control flow logic are somewhat dependent on the functions themselves, it is a logical step to first identify the functions within a process. This research addresses the current gap in knowledge by developing a method to identify functions common to various industry types (termed core functions). This lays the foundation to extract such functions, so as to identify both commonalities and variation points in asset management processes. This method describes the use of a manual text mining and a taxonomy approach. An example is presented.

In the Solanaceae, a hierarchy of bHLHs confer distinct target specificity to the anthocyanin regulatory complex

The anthocyanin biosynthetic pathway is regulated by a transcription factor complex consisting of an R2R3 MYB, a bHLH, and a WD40. Although R2R3 MYBs belonging to the anthocyanin-activating class have been identified in many plants, and their role well elucidated, the subgroups of bHLH implicated in anthocyanin regulation seem to be more complex. It is not clear whether these potential bHLH partners are biologically interchangeable with redundant functions, or even if heterodimers are involved. In this study, AcMYB110, an R2R3 MYB isolated from kiwifruit (Actinidia sp.) showing a strong activation of the anthocyanin pathway in tobacco (Nicotiana tabacum) was used to examine the function of interacting endogenous bHLH partners. Constitutive expression of AcMYB110 in tobacco leaves revealed different roles for two bHLHs, NtAN1 and NtJAF13. A hierarchical mechanism is shown to control the regulation of transcription factors and consequently of the anthocyanin biosynthetic pathway. Here, a model is proposed for the regulation of the anthocyanin pathway in Solanaceous plants in which AN1 is directly involved in the activation of the biosynthetic genes, whereas JAF13 is involved in the regulation of AN1 transcription.

Identification of a BRCA1-mRNA splicing complex required for efficient DNA repair and maintenance of genomic stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage.

Identifying the molecular mediators of VN and the IGF:VN complex-stimulated breast cancer cell survival

This project has identified a molecular signature involved in functions critical to breast cancer progression and metastasis mediated by vitronectin, an abundant protein in human plasma and victornectin:insulin-like growth factor complexes. This may have significant implications in designing future therapeutic targets for patient with tumours overexpressing vitronectin and/or the components of the insulin-like growth factor system:vitronectin axis. In particular, the findings from this project have identified Cyr61 and CTGF as key mediators involved in vitroncetin- and insulin-like growth factor I: Insulin-like growth factor-binding protein:vitronectin-induced breast cancer cell survival and migration.

A new twist on mode indicator functions

Mode indicator functions (MIFs) are used in modal testing and analysis as a means of identifying modes of vibration, often as a precursor to modal parameter estimation. Various methods have been developed since the MIF was introduced four decades ago. These methods are quite useful in assisting the analyst to identify genuine modes and, in the case of the complex mode indicator function, have even been developed into modal parameter estimation techniques. Although the various MIFs are able to indicate the existence of a mode, they do not provide the analyst with any descriptive information about the mode. This paper uses the simple summation type of MIF to develop five averaged and normalised MIFs that will provide the analyst with enough information to identify whether a mode is longitudinal, vertical, lateral or torsional. The first three functions, termed directional MIFs, have been noted in the literature in one form or another; however, this paper introduces a new twist on the MIF by introducing two MIFs, termed torsional MIFs, that can be used by the analyst to identify torsional modes and, moreover, can assist in determining whether the mode is of a pure torsion or sway type (i.e., having a rigid cross-section) or a distorted twisting type. The directional and torsional MIFs are tested on a finite element model based simulation of an experimental modal test using an impact hammer. Results indicate that the directional and torsional MIFs are indeed useful in assisting the analyst to identify whether a mode is longitudinal, vertical, lateral, sway, or torsion.