What are the offence and offender risk factors for Indigenous repeat drink drivers in Queensland Australia?

Background Road crashes contribute to high injury rates in Indigenous population in Aust, NZ, Canada and USA Alcohol one of the leading risk factors for road crashes: 31.5% Indigenous drivers in remote areas over 0.05mg/100ml, compared to 7.4 percent of non-Indigenous counterparts 17.5% Indigenous drivers in regional areas over 0.05mg/100ml compared to 3.8 percent of non-Indigenous counterparts Indigenous peoples are overrepresented in alcohol-related fatality rates, with this group 40% more likely to be killed

Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene KCNN3 and migraine susceptibility

Background Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels. Methods The present association study tested whether length variations in the second (more 3') polymorphic CAG repeat in exon 1 of the KCNN3 gene, are involved in susceptibility to migraine with and without aura (MA and MO). In total 423 DNA samples from unrelated individuals, of which 202 consisted of migraine patients and 221 non-migraine controls, were genotyped and analysed using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele frequencies were calculated from observed genotype counts for the KCNN3 polymorphism. Analysis was performed using standard contingency table analysis, incorporating the chi-squared test of independence and CLUMP analysis. Results Overall, there was no convincing evidence that KCNN3 CAG lengths differ between Caucasian migraineurs and controls, with no significant difference in the allelic length distribution of CAG repeats between the population groups (P = 0.090). Also the MA and MO subtypes did not differ significantly between control allelic distributions (P > 0.05). The prevalence of the long CAG repeat (>19 repeats) did not reach statistical significance in migraineurs (P = 0.15), nor was there a significant difference between the MA and MO subgroups observed compared to controls (P = 0.46 and P = 0.09, respectively), or between MA vs MO (P = 0.40). Conclusion This association study provides no evidence that length variations of the second polyglutamine array in the N-terminus of the KCNN3 channel exert an effect in the pathogenesis of migraine.

A linkage and cross-sectional study of hypertension and obesity using a poly(A) Alu-repeat polymorphism at the glucagon receptor gene locus (17q25)

1. Previous glucagon receptor gene (GCGR) studies have shown a Gly40Ser mutation to be more prevalent in essential hypertension and to affect glucagon binding affinity to its receptor. An Alu-repeat poly(A) polymorphism colocalized to GCGR was used in the present study to test for association and linkage in hypertension as well as association in obesity development. 2. Using a cross-sectional approach, 85 hypertensives and 95 normotensives were genotyped using polymerase chain reaction primers flanking the Alu-repeat. Both hypertensive and normotensive populations were subdivided into lean and obese categories based on body mass index (BMI) to determine involvement of this variant in obesity. For the linkage study, 89 Australian Caucasian hypertension affected sibships (174 sibpairs) were genotyped and the results were analysed using GENE-HUNTER, Mapmaker Sibs, ERPA and SPLINK (all freely available from http://linlkage.rockefeller. edu/soft/list.html). 3. Cross-sectional results for both hypertension and obesity were analysed using Chi-squared and Monte Carlo analyses. Results did not show an association of this variant with either hypertension (χ2 = 6.9, P = 0.14; Monte Carlo χ2 = 7.0, P = 0.11; n = 5000) or obesity (χ2 = 3.3, P = 0.35; Monte Carlo χ2 = 3.26, P = 0.34; n = 5000). In addition, results from the linkage study using hypertensive sib-pairs did not indicate linkage of the poly(A) repent with hypertension. Hence, results did not indicate a role far the Alu-repeat in either hypertension or obesity. However, as the heterozygosity of this poly(A) repeat is low (35%), a larger number of hypertensive sib-pairs may be required to draw definitive conclusions.

Polyalanine repeat polymorphism in RUNX2 is associated with site-specific fracture in post-menopausal females

Runt related transcription factor 2 (RUNX2) is a key regulator of osteoblast differentiation. Several variations within RUNX2 have been found to be associated with significant changes in BMD, which is a major risk factor for fracture. In this study we report that an 18bp deletion within the polyalanine tract (17A>11A) of RUNX2 is significantly associated with fracture. Carriers of the 11A allele were found to be nearly twice as likely to have sustained fracture. Within the fracture category, there was a significant tendency of 11A carriers to present with fractures of bones of intramembranous origin compared to bones of endochondral origin (p=0.005). In a population of random subjects, the 11A allele was associated with decreased levels of serum collagen cross links (CTx, p=0.01), suggesting decreased bone turnover. The transactivation function of the 11A allele was quantitatively decreased. Interestingly, we found no effect of the 11A allele on BMD at multiple skeletal sites, although these were not the sites where a relationship with fracture was most evident. These findings suggest that the 11A allele is a biologically relevant polymorphism that influences serum CTx and confers enhanced fracture risk in a site-selective manner related to intramembranous bone ossification.

Reduced biceps femoris myoelectrical activity influences eccentric knee flexor weakness after repeat sprint running

The aim of this study was to determine whether declines in knee flexor strength following overground repeat sprints were related to changes in hamstrings myoelectrical activity. Seventeen recreationally active males completed maximal isokinetic concentric and eccentric knee flexor strength assessments at 1800.s-1 before and after repeat sprint running. Myoelectrical activity of the biceps femoris (BF) and medial hamstrings (MH) was measured during all isokinetic contractions. Repeated measures mixed model (Fixed factors = time [pre- and post- repeat sprint] and leg [dominant and non-dominant], random factor = participants) design was fitted with the restricted maximal likelihood method. Repeat sprint running resulted in significant declines in eccentric, and concentric, knee flexor strength (eccentric = 25 ± 34 Nm, 15% p<0.001; concentric 11 Nm± 22 Nm, 10% p = 0.001). Eccentric BF myoelectrical activity was significantly reduced (10%; p= 0.033). Concentric BF and all MH myoelectrical activity were not altered. The declines in maximal eccentric torque were associated with the change in eccentric biceps femoris myoelectrical activity (p = 0.013). Following repeat sprint running there were preferential declines in the myoelectrical activity of the BF, which explained declines in eccentric knee flexor strength.

A variant of the breast cancer type 2 susceptibility protein (BRC) repeat is essential for the RECQL5 Helicase to interact with RAD51 Recombinase for genome stabilization

The BRC repeat is a structural motif in the tumor suppressor BRCA2 (breast cancer type 2 susceptibility protein), which promotes homologous recombination (HR) by regulating RAD51 recombinase activity. To date, the BRC repeat has not been observed in other proteins, so that its role in HR is inferred only in the context of BRCA2. Here, we identified a BRC repeat variant, named BRCv, in the RECQL5 helicase, which possesses anti-recombinase activity in vitro and suppresses HR and promotes cellular resistance to camptothecin-induced replication stress in vivo. RECQL5-BRCv interacted with RAD51 through two conserved motifs similar to those in the BRCA2-BRC repeat. Mutations of either motif compromised functions of RECQL5, including association with RAD51, inhibition of RAD51-mediated D-loop formation, suppression of sister chromatid exchange, and resistance to camptothecin-induced replication stress. Potential BRCvs were also found in other HR regulatory proteins, including Srs2 and Sgs1, which possess anti-recombinase activities similar to that of RECQL5. A point mutation in the predicted Srs2-BRCv disrupted the ability of the protein to bind RAD51 and to inhibit D-loop formation. Thus, BRC is a common RAD51 interaction module that can be utilized by different proteins to either promote HR, as in the case of BRCA2, or to suppress HR, as in RECQL5.

UafB is a serine-rich repeat adhesin of Staphylococcus saprophyticus that mediates binding to fibronectin, fibrinogen and human uroepithelial cells

Staphylococcus saprophyticus is an important cause of urinary tract infection (UTI), particularly among young women, and is second only to uropathogenic Escherichia coli as the most frequent cause of UTI. The molecular mechanisms of urinary tract colonization by S. saprophyticus remain poorly understood. We have identified a novel 6.84 kb plasmid-located adhesin-encoding gene in S. saprophyticus strain MS1146 which we have termed uro-adherence factor B (uafB). UafB is a glycosylated serine-rich repeat protein that is expressed on the surface of S. saprophyticus MS1146. UafB also functions as a major cell surface hydrophobicity factor. To characterize the role of UafB we generated an isogenic uafB mutant in S. saprophyticus MS1146 by interruption with a group II intron. The uafB mutant had a significantly reduced ability to bind to fibronectin and fibrinogen. Furthermore, we show that a recombinant protein containing the putative binding domain of UafB binds specifically to fibronectin and fibrinogen. UafB was not involved in adhesion in a mouse model of UTI; however, we observed a striking UafB-mediated adhesion phenotype to human uroepithelial cells. We have also identified genes homologous to uafB in other staphylococci which, like uafB, appear to be located on transposable elements. Thus, our data indicate that UafB is a novel adhesin of S. saprophyticus that contributes to cell surface hydrophobicity, mediates adhesion to fibronectin and fibrinogen, and exhibits tropism for human uroepithelial cells.

The plasticity of NBS resistance genes in sorghum is driven by multiple evolutionary processes

Background Increased disease resistance is a key target of cereal breeding programs, with disease outbreaks continuing to threaten global food production, particularly in Africa. Of the disease resistance gene families, the nucleotide-binding site plus leucine-rich repeat (NBS-LRR) family is the most prevalent and ancient and is also one of the largest gene families known in plants. The sequence diversity in NBS-encoding genes was explored in sorghum, a critical food staple in Africa, with comparisons to rice and maize and with comparisons to fungal pathogen resistance QTL. Results In sorghum, NBS-encoding genes had significantly higher diversity in comparison to non NBS-encoding genes and were significantly enriched in regions of the genome under purifying and balancing selection, both through domestication and improvement. Ancestral genes, pre-dating species divergence, were more abundant in regions with signatures of selection than in regions not under selection. Sorghum NBS-encoding genes were also significantly enriched in the regions of the genome containing fungal pathogen disease resistance QTL; with the diversity of the NBS-encoding genes influenced by the type of co-locating biotic stress resistance QTL. Conclusions NBS-encoding genes are under strong selection pressure in sorghum, through the contrasting evolutionary processes of purifying and balancing selection. Such contrasting evolutionary processes have impacted ancestral genes more than species-specific genes. Fungal disease resistance hot-spots in the genome, with resistance against multiple pathogens, provides further insight into the mechanisms that cereals use in the “arms race” with rapidly evolving pathogens in addition to providing plant breeders with selection targets for fast-tracking the development of high performing varieties with more durable pathogen resistance.

Franklin Barley: Patent law and plant breeders’ rights

This paper considers the relationship between patent law and plant breeders' rights in light of modern developments in biotechnology. It examines how a number of superior courts have sought to manage the tensions and conflicts between these competing schemes of intellectual property protection. Part 1 considers the High Court of Australia case of Grain Pool of Western Australia v the Commonwealth dealing with Franklin barley. Part 2 examines the significance of the Supreme Court of the United States decision in JEM Ag Supply Inc v Pioneer Hi-Bred International Inc with respect to utility patents and hybrid seed. Part 3 considers the Supreme Court of Canada case of Harvard College v the Commissioner of Patents dealing with the transgenic animal, oncomouse, and discusses its implications for the forthcoming appeal from the Federal Court case of Percy Schmeiser v Monsanto.

Investigating the population structure of Queensland invasive Streptococcus pneumoniae isolates in children: Using a modified multi-locus variable number of tandem repeat analysis and a novel minimum SNPs capsular typing method

This research investigated the use of DNA fingerprinting to characterise the bacteria Streptococcus pneumoniae or pneumococcus, and hence gain insight into the development of new vaccines or antibiotics. Different bacterial DNA fingerprinting methods were studied, and a novel method was developed and validated, which characterises different cell coatings that pneumococci produce. This method was used to study the epidemiology of pneumococci in Queensland before and after the introduction of the current pneumococcal vaccine. This study demonstrated that pneumococcal disease is highly prevalent in children under four years, that the bacteria can `switch' its cell coating to evade the vaccine, and that some DNA fingerprinting methods are more discriminatory than others. This has an impact on understanding which strains are more prone to cause invasive disease. Evidence of the excellent research findings have been published in high impact internationally refereed journals.

Association of FOXE1 Polyalanine Repeat Region with Papillary Thyroid Cancer

CONTEXT: Polyalanine tract variations in transcription factors have been identified for a wide spectrum of developmental disorders. The thyroid transcription factor forkhead factor E1 (FOXE1) contains a polymorphic polyalanine tract with 12-22 alanines. Single-nucleotide polymorphisms (SNP) close to this locus are associated with papillary thyroid cancer (PTC), and a strong linkage disequilibrium block extends across this region. OBJECTIVE: The objective of the study was to assess whether the FOXE1 polyalanine repeat region was associated with PTC and to assess the effect of polyalanine repeat region variants on protein expression, DNA binding, and transcriptional function on FOXE1-responsive promoters. DESIGN: This was a case-control study. SETTING: The study was conducted at a tertiary referral hospital. PATIENTS AND METHODS: The FOXE1 polyalanine repeat region and tag SNP were genotyped in 70 PTC, with a replication in a further 92 PTC, and compared with genotypes in 5767 healthy controls (including 5667 samples from the Wellcome Trust Case Control Consortium). In vitro studies were performed to examine the protein expression, DNA binding, and transcriptional function for FOXE1 variants of different polyalanine tract lengths. RESULTS: All the genotyped SNP were in tight linkage disequilibrium, including the FOXE1 polyalanine repeat region. We confirmed the strong association of rs1867277 with PTC (overall P = 1 × 10(-7), odds ratio 1.84, confidence interval 1.31-2.57). rs1867277 was in tight linkage disequilibrium with the FOXE1 polyalanine repeat region (r(2) = 0.95). FOXE1(16Ala) was associated with PTC with an odds ratio of 2.23 (confidence interval 1.42-3.50; P = 0.0005). Functional studies in vitro showed that FOXE1(16Ala) was transcriptionally impaired compared with FOXE1(14Ala), which was not due to differences in protein expression or DNA binding. CONCLUSIONS: We have confirmed the previous association of FOXE1 with PTC. Our data suggest that the coding polyalanine expansion in FOXE1 may be responsible for the observed association between FOXE1 and PTC.

Why, how, what for? : motivations, actions and expectations in habitual entrepreneurship

Principal topic: Is habitual entrepreneurship different? Answering this is important to the field, however there is little systematic evidence, thus far. We addresses this by examining the role experience plays at three possible points of difference: motivations, actions and expectations; and by comparing those currently in the process of starting a business with those who have recent success in business creation. Firstly, we assess the balance of opportunity versus necessity motivation, internally versus externally stimulated decision processes and future growth aspirations. Literature suggests novices are more likely motivated to nascency out of necessity, and favour a manageable business size, while habitual entrepreneurs are more likely motivated by internally stimulated or idea driven processes. Secondly, we examine actions undertaken by successful experienced founders during gestation, contrasting ‘information collection’ and ‘opportunity definition’. Drawing on prior research we expect novices more likely to have enacted ‘information search’ while habitual entrepreneurs enact ‘opportunity definition’. Thirdly, we examine perceptions of venture success, where findings on overconfidence suggest that habitual entrepreneurs expect a higher chance of success for their ventures, while inexperience leads novices to underestimate the difficulty of entrepreneurial survival. Method: Empirical evidence to test these conjectures was drawn from a screened random sample of over 1100 Australian nascent and newly started business ventures. This information was collected during 2007/8 using a telephone survey. Results and Implications: Why do habitual entrepreneurs keep coming back? Findings suggest that while the pursuit of opportunity is shared by novice and experienced entrepreneur alike, consideration of repeat entrepreneurship may be motivated by a desire for growth. While idea driven motivations might not delineate a distinction during nascency, it does seem to be a factor contributing to the success of young firms. This warrants further research. How do habitual entrepreneurs behave differently? It seems they act to clearly define market opportunities as a matter of priority during venture gestation. What effect does entrepreneurial experience have on future expectations? Clearly a sense of realism is drawn over the difficulties that might be faced, and accords more circumspect judgements of venture survival. This finding informs practitioners considering entrepreneurship for the first time.

Project learning through project histories

Many people and organisations continually repeat mistakes or fail to take advantage of opportunities because they have not learned from their past history, frequently as a result of not having taken the time to reflect and take stock of their experiences. This common error is avoidable, particularly with today’s capacity for information and communication technology (ICT) to enable organisations to not only record lessons learned but to easily make these available throughout an organisation. Moreover, the evidence of the literature and experience suggests that currently companies do not rigorously analyse past experience and log lessons learned using manual methods so it is hardly surprising that this trend is not changed by the availability of ICT.

Boys 'doing' and 'undoing' media education : new possibilities for theory and practice

The purpose of this study is to investigate how secondary school media educators might best meet the needs of students who prefer practical production work to ‘theory’ work in media studies classrooms. This is a significant problem for a curriculum area that claims to develop students’ media literacies by providing them with critical frameworks and a metalanguage for thinking about the media. It is a problem that seems to have become more urgent with the availability of new media technologies and forms like video games. The study is located in the field of media education, which tends to draw on structuralist understandings of the relationships between young people and media and suggests that students can be empowered to resist media’s persuasive discourses. Recent theoretical developments suggest too little emphasis has been placed on the participatory aspects of young people playing with, creating and gaining pleasure from media. This study contributes to this ‘participatory’ approach by bringing post structuralist perspectives to the field, which have been absent from studies of secondary school media education. I suggest theories of media learning must take account of the ongoing formation of students’ subjectivities as they negotiate social, cultural and educational norms. Michel Foucault’s theory of ‘technologies of the self’ and Judith Butler’s theories of performativity and recognition are used to develop an argument that media learning occurs in the context of students negotiating various ‘ethical systems’ as they establish their social viability through achieving recognition within communities of practice. The concept of ‘ethical systems’ has been developed for this study by drawing on Foucault’s theories of discourse and ‘truth regimes’ and Butler’s updating of Althusser’s theory of interpellation. This post structuralist approach makes it possible to investigate the ways in which students productively repeat and vary norms to creatively ‘do’ and ‘undo’ the various media learning activities with which they are required to engage. The study focuses on a group of year ten students in an all boys’ Catholic urban school in Australia who undertook learning about video games in a three-week intensive ‘immersion’ program. The analysis examines the ethical systems operating in the classroom, including formal systems of schooling, informal systems of popular cultural practice and systems of masculinity. It also examines the students’ use of semiotic resources to repeat and/or vary norms while reflecting on, discussing, designing and producing video games. The key findings of the study are that students are motivated to learn technology skills and production processes rather than ‘theory’ work. This motivation stems from the students’ desire to become recognisable in communities of technological and masculine practice. However, student agency is not only possible through critical responses to media, but through performative variation of norms through creative ethical practices as students participate with new media technologies. Therefore, the opportunities exist for media educators to create the conditions for variation of norms through production activities. The study offers several implications for media education theory and practice including: the productive possibilities of post structuralism for informing ways of doing media education; the importance of media teachers having the autonomy to creatively plan curriculum; the advantages of media and technology teachers collaborating to draw on a broad range of resources to develop curriculum; the benefits of placing more emphasis on students’ creative uses of media; and the advantages of blending formal classroom approaches to media education with less formal out of school experiences.