Phylogeographic reconstruction of a bacterial species with high levels of lateral gene transfer

Background Phylogeographic reconstruction of some bacterial populations is hindered by low diversity coupled with high levels of lateral gene transfer. A comparison of recombination levels and diversity at seven housekeeping genes for eleven bacterial species, most of which are commonly cited as having high levels of lateral gene transfer shows that the relative contributions of homologous recombination versus mutation for Burkholderia pseudomallei is over two times higher than for Streptococcus pneumoniae and is thus the highest value yet reported in bacteria. Despite the potential for homologous recombination to increase diversity, B. pseudomallei exhibits a relative lack of diversity at these loci. In these situations, whole genome genotyping of orthologous shared single nucleotide polymorphism loci, discovered using next generation sequencing technologies, can provide very large data sets capable of estimating core phylogenetic relationships. We compared and searched 43 whole genome sequences of B. pseudomallei and its closest relatives for single nucleotide polymorphisms in orthologous shared regions to use in phylogenetic reconstruction. Results Bayesian phylogenetic analyses of >14,000 single nucleotide polymorphisms yielded completely resolved trees for these 43 strains with high levels of statistical support. These results enable a better understanding of a separate analysis of population differentiation among >1,700 B. pseudomallei isolates as defined by sequence data from seven housekeeping genes. We analyzed this larger data set for population structure and allele sharing that can be attributed to lateral gene transfer. Our results suggest that despite an almost panmictic population, we can detect two distinct populations of B. pseudomallei that conform to biogeographic patterns found in many plant and animal species. That is, separation along Wallace's Line, a biogeographic boundary between Southeast Asia and Australia. Conclusion We describe an Australian origin for B. pseudomallei, characterized by a single introduction event into Southeast Asia during a recent glacial period, and variable levels of lateral gene transfer within populations. These patterns provide insights into mechanisms of genetic diversification in B. pseudomallei and its closest relatives, and provide a framework for integrating the traditionally separate fields of population genetics and phylogenetics for other bacterial species with high levels of lateral gene transfer.

Expression of PSA-RP2, an alternatively spliced variant from the PSA gene, is increased in prostate cancer tissues but the protein is not secreted from prostate cancer cells

PSA-RP2 is a variant transcript expressed from the PSA gene that is conserved in gorillas, chimpanzees and humans suggesting a particular relevance for this transcript in these primates. We demonstrated by qRT-PCR that PSA-RP2 is upregulated in prostate cancer compared with benign prostatic hyperplasia tissues. The PSA-RP2 protein was not detected in seminal fluid and was cytoplasmically localised but not secreted from LNCaP or transfected PC3 prostate cells, despite secretion from transfected Cos-7 and HEK293 kidney cell lines. PSA-RP2-transfected PC3 cells showed slightly decreased proliferation and increased migration towards PC3-conditioned medium that could suggest a functional role in prostate cancer.

A conceptual decision-making framework for the delivery of innovative change in organisations

Research found that today’s organisations are increasingly aware of the potential barriers and perceived challenges associated with the successful delivery of change — including cultural and sub-cultural indifferences; financial constraints; restricted timelines; insufficient senior management support; fragmented key stakeholder commitment; and inadequate training. The delivery and application of Innovative Change (see glossary) within a construction industry organisation tends to require a certain level of ‘readiness’. This readiness is the combination of an organisation’s ability to part from undertakings that may be old, traditional, or inefficient; and then being able to readily adopt a procedure or initiative which is new, improved, or more efficient. Despite the construction industry’s awareness of the various threats and opportunities associated with the delivery of change, research found little attention is currently given to develop a ‘decision-making framework’ that comprises measurable elements (dynamics) that may assist in more accurately determining an organisation’s level of readiness or ability to deliver innovative change. To resolve this, an initial Background Literature Review in 2004 identified six such dynamics, those of Change, Innovation, Implementation, Culture, Leadership, and Training and Education, which were then hypothesised to be key components of a ‘Conceptual Decision-making Framework’ (CDF) for delivering innovative change within an organisation. To support this hypothesis, a second (more extensive) Literature Review was undertaken from late 2007 to mid 2009. A Delphi study was embarked on in June 2008, inviting fifteen building and construction industry members to form a panel and take part in a Delphi study. The selection criterion required panel members to have senior positions (manager and above) within a recognised field or occupation, and to have experience, understanding and / or knowledge in the process of delivering change within organisations. The final panel comprised nine representatives from private and public industry organisations and tertiary / research and development (R&D) universities. The Delphi study developed, distributed and collated two rounds of survey questionnaires over a four-month period, comprising open-ended and closed questions (referred to as factors). The first round of Delphi survey questionnaires were distributed to the panel in August 2008, asking them to rate the relevancy of the six hypothesised dynamics. In early September 2008, round-one responses were returned, analysed and documented. From this, an additional three dynamics were identified and confirmed by the panel as being highly relevant during the decision-making process when delivering innovative change within an organisation. The additional dynamics (‘Knowledge-sharing and Management’; ‘Business Process Requirements’; and ‘Life-cycle Costs’) were then added to the first six dynamics and used to populate the second (final) Delphi survey questionnaire. This was distributed to the same nine panel members in October 2008, this time asking them to rate the relevancy of all nine dynamics. In November 2008, round-two responses were returned, analysed, summarised and documented. Final results confirmed stability in responses and met Delphi study guidelines. The final contribution is twofold. Firstly, findings confirm all nine dynamics as key components of the proposed CDF for delivering innovative change within an organisation. Secondly, the future development and testing of an ‘Innovative Change Delivery Process’ (ICDP) is proposed, one that is underpinned by an ‘Innovative Change Decision-making Framework’ (ICDF), an ‘Innovative Change Delivery Analysis’ (ICDA) program, and an ‘Innovative Change Delivery Guide’ (ICDG).

Common variation in the fibroblast growth factor receptor 2 gene is not associated with endometriosis risk

BACKGROUND Endometriosis is a polygenic disease with a complex and multifactorial aetiology that affects 8-10% of women of reproductive age. Epidemiological data support a link between endometriosis and cancers of the reproductive tract. Fibroblast growth factor receptor 2 (FGFR2) has recently been implicated in both endometrial and breast cancer. Our previous studies on endometriosis identified significant linkage to a novel susceptibility locus on chromosome 10q26 and the FGFR2 gene maps within this linkage region. We therefore hypothesized that variation in FGFR2 may contribute to the risk of endometriosis. METHODS We genotyped 13 single nucleotide polymorphisms (SNPs) densely covering a 27 kb region within intron 2 of FGFR2 including two SNPs (rs2981582 and rs1219648) significantly associated with breast cancer and a total 40 tagSNPs across 150 kb of the FGFR2 gene. SNPs were genotyped in 958 endometriosis cases and 959 unrelated controls. RESULTS We found no evidence for association between endometriosis and FGFR2 intron 2 SNPs or SNP haplotypes and no evidence for association between endometriosis and variation across the FGFR2 gene. CONCLUSIONS Common variation in the breast-cancer implicated intron 2 and other highly plausible causative candidate regions of FGFR2 do not appear to be a major contributor to endometriosis susceptibility in our large Australian sample.