Psip1/Ledgf p52 binds methylated histone H3K36 and splicing factors and contributes to the regulation of alternative splicing

Increasing evidence suggests that chromatin modifications have important roles in modulating constitutive or alternative splicing. Here we demonstrate that the PWWP domain of the chromatin-associated protein Psip1/Ledgf can specifically recognize tri-methylated H3K36 and that, like this histone modification, the Psip1 short (p52) isoform is enriched at active genes. We show that the p52, but not the long (p75), isoform of Psip1 co-localizes and interacts with Srsf1 and other proteins involved in mRNA processing. The level of H3K36me3 associated Srsf1 is reduced in Psip1 mutant cells and alternative splicing of specific genes is affected. Moreover, we show altered Srsf1 distribution around the alternatively spliced exons of these genes in Psip1 null cells. We propose that Psip1/p52, through its binding to both chromatin and splicing factors, might act to modulate splicing.

An urban design perspective to classify knowledge precincts : a typological analysis of global best practices

Purpose: The paper seeks to investigate emerging knowledge precincts under the urban design lens in order to identify recurrent spatial patterns of urban forms and functions to gather an understanding of physical aspects that contribute to the creation of place quality. Scope: This paper focuses on the physical design and layout of specific precincts. Although socio-economic and other factors come into play imparting the distinctiveness; this paper only focuses on the spatial dimensions. Method: The research first develops a design typology framework through the lead of literature, and then utilizes it to identify recurrent elements in knowledge precinct design in order to develop taxonomy of patterns and layouts. Results: The research reported in this paper provides preliminary insights into the various form and functional factors playing role in the design of knowledge precincts and evaluates the elements that contribute to the success of these urban interventions. Recommendations: The paper recommends the use of particular design-based solutions in order to enhance the place making in knowledge precincts. Conclusions: The study concludes that despite the locational, regulatory and other contextual differences, the underlying driving principle of providing place quality to people leads to the emergence of identifiable spatial patterns across the knowledge precincts.

Profiling contextual factors which influence safety in heavy vehicle industries

A significant proportion of worker fatalities within Australia result from truck-related incidents. Truck drivers face a number of health and safety concerns. Safety culture, viewed here as the beliefs, attitudes and values shared by an organisation’s workers, which interact with their surrounding context to influence behaviour, may provide a valuable lens for exploring safety-related behaviours in heavy vehicle operations. To date no major research has examined safety culture within heavy vehicle industries. As safety culture provides a means to interpret experiences and generate behaviour, safety culture research should be conducted with an awareness of the context surrounding safety. The current research sought to examine previous health and safety research regarding heavy vehicle operations to profile contextual factors which influence health and safety. A review of 104 peer-reviewed papers was conducted. Findings of these papers were then thematically analysed. A number of behaviours and scenarios linked with crashes and non-crash injuries were identified, along with a selection of health outcomes. Contextual factors which were found to influence these outcomes were explored. These factors were found to originate from government departments, transport organisations, customers and the road and work environment. The identified factors may provide points of interaction, whereby culture may influence health and safety outcomes.

Factors affecting new project delays in Saudi Arabian manufacturing organisations

Delay in the delivery of manufacturing projects is a major problem in manufacturing industries. This research investigates the factors that influence the lead time of new projects in manufacturing organisations. Employing a questionnaire survey and interview methodologies, this study collected data from five leading manufacturing organisations as well as their suppliers and contractors in Saudi Arabia to examine what, how and why the new project implementation delay occurs. Results show that the main factors contributing to manufacturing delays are related to people and material. On the other hand, social, political and cultural factors were the least significant factors as per the outcome of this study. Views of manufacturers, suppliers and contractors regarding causes of delays have also been analysed.

Spatial analysis of risk factors for transmission of the Barmah forest virus in Queensland, Australia

Barmah Forest virus (BFV) disease is the second most common mosquito-borne disease in Australia but few data are available on the risk factors. We assessed the impact of spatial climatic, socioeconomic and ecological factors on the transmission of BFV disease in Queensland, Australia, using spatial regression. All our analyses indicate that spatial lag models provide a superior fit to the data compared to spatial error and ordinary least square models. The residuals of the spatial lag models were found to be uncorrelated, indicating that the models adequately account for spatial and temporal autocorrelation. Our results revealed that minimum temperature, distance from coast and low tide were negatively and rainfall was positively associated with BFV disease in coastal areas, whereas minimum temperature and high tide were negatively and rainfall was positively associated with BFV disease (all P-value.

Molecular characterization of the EhaG and UpaG trimeric autotransporter proteins from pathogenic Escherichia coli

Trimeric autotransporter proteins (TAAs) are important virulence factors of many Gram-negative bacterial pathogens. A common feature of most TAAs is the ability to mediate adherence to eukaryotic cells or extracellular matrix (ECM) proteins via a cell surface-exposed passenger domain. Here we describe the characterization of EhaG, a TAA identified from enterohemorrhagic Escherichia coli (EHEC) O157:H7. EhaG is a positional orthologue of the recently characterized UpaG TAA from uropathogenic E. coli (UPEC). Similarly to UpaG, EhaG localized at the bacterial cell surface and promoted cell aggregation, biofilm formation, and adherence to a range of ECM proteins. However, the two orthologues display differential cellular binding: EhaG mediates specific adhesion to colorectal epithelial cells while UpaG promotes specific binding to bladder epithelial cells. The EhaG and UpaG TAAs contain extensive sequence divergence in their respective passenger domains that could account for these differences. Indeed, sequence analyses of UpaG and EhaG homologues from several E. coli genomes revealed grouping of the proteins in clades almost exclusively represented by distinct E. coli pathotypes. The expression of EhaG (in EHEC) and UpaG (in UPEC) was also investigated and shown to be significantly enhanced in an hns isogenic mutant, suggesting that H-NS acts as a negative regulator of both TAAs. Thus, while the EhaG and UpaG TAAs contain some conserved binding and regulatory features, they also possess important differences that correlate with the distinct pathogenic lifestyles of EHEC and UPEC.

Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli

The majority of Escherichia coli strains isolated from urinary tract infections have the potential to express multiple fimbriae. Two of the most common fimbrial adhesins are type 1 fimbriae and pyelonephritis-associated pili (Pap). Previous research has shown that induced, plasmid-based expression of a Pap regulator, papB, and its close homologues can prevent inversion of the fim switch controlling the expression of type 1 fimbriae. The aim of the present study was to determine if this cross-regulation occurs when PapB is expressed from its native promoter in the chromosome of E. coli K-12 and clinical isolates. The regulation was examined in three ways: (1) mutated alleles of the pap regulatory region, including papB and papI, that maintain the pap promoter in either the off or the on phase were exchanged into the chromosome of both E. coli K-12 and the clinical isolate E. coli CFT073, and the effect on type 1 fimbrial expression was measured; (2) type 1 fimbrial expression was determined using a novel fimS : : gfp+ reporter system in mutants of the clinical isolate E. coli 536 in which combinations of complete fimbrial clusters had been deleted; (3) type 1 fimbrial expression was determined in a range of clinical isolates and compared with both the number of P clusters and their expression. All three approaches demonstrated that P expression represses type 1 fimbrial expression. Using a number of novel genetic approaches, this work extends the initial finding that PapB inhibits FimB recombination to the impact of this regulation in clinical isolates.