Evidence for three tumor suppressor loci on chromosome 9p involved in melanoma development

Cytogenetic and loss of heterozygosity (LOH) studies have long indicated the presence of a tumor suppressor gene (TSG) on 9p involved in the development of melanoma. Although LOH at 9p has been reported in approximately 60% of melanoma tumors, only 5-10% of these tumors have been shown to carry CDKN2A mutations, raising the possibility that another TSG involved in melanoma maps to chromosome 9p. To investigate this possibility, a panel of 37 melanomas derived from 35 individuals was analyzed for CDKN2A mutations by single-strand conformation polymorphism analysis and sequencing. The melanoma samples were then typed for 15 markers that map to 9p13-24 to investigate LOH trends in this region. In those tumors demonstrating retention of heterozygosity at markers flanking CDKN2A and LOH on one or both sides of the gene, multiplex microsatellite PCR was performed to rule out homozygous deletion of the region encompassing CDKN2A. CDKN2A mutations were found in tumors from 5 patients [5 (14%) of 35], 4 of which demonstrated LOH across the entire region examined. The remaining tumor with no observed LOH carried two point mutations, one on each allele. Although LOH was identified at one or more markers in 22 (59%) of 37 melanoma tumors corresponding to 20 (57%) of 35 individuals, only 11 tumors from 9 individuals [9 (26%) of 35] demonstrated LOH at D9S942 and D9S1748 the markers closest to CDKN2A. Of the remaining 11 tumors with LOH 9 demonstrated LOH at two or more contiguous markers either centromeric and/or telomeric to CDKN2A while retaining heterozygosity at several markers adjacent to CDKN2A. Multiplex PCR revealed one tumor carried a homozygous deletion extending from D9S1748 to the IFN-alpha locus. In the remaining eight tumors, multiplex PCR demonstrated that the observed heterozygosity was not attributable to homozygous deletion and stromal contamination at D9S1748, D9S942, or D9S974, as measured by comparative amplification strengths, which indicates that retention of heterozygosity with flanking LOH does not always indicate a homozygous deletion. This report supports the conclusions of previous studies that a least two TSGs involved in melanoma development in addition to CDKN2A may reside on chromosome 9p.

Modelling and performance evaluation of the IEEE 802.11 DCF for real-time control

Popular wireless networks, such as IEEE 802.11/15/16, are not designed for real-time applications. Thus, supporting real-time quality of service (QoS) in wireless real-time control is challenging. This paper adopts the widely used IEEE 802.11, with the focus on its distributed coordination function (DCF), for soft-real-time control systems. The concept of the critical real-time traffic condition is introduced to characterize the marginal satisfaction of real-time requirements. Then, mathematical models are developed to describe the dynamics of DCF based real-time control networks with periodic traffic, a unique feature of control systems. Performance indices such as throughput and packet delay are evaluated using the developed models, particularly under the critical real-time traffic condition. Finally, the proposed modelling is applied to traffic rate control for cross-layer networked control system design.

Implementation of ICD-11... perspectives from the Australian Bureau of Statistics

As the development of ICD-11 progresses, the Australian Bureau of Statistics is beginning to consider what will be required to successfully implement the new version of the classification. This paper will present early thoughts on the following: building understanding amongst the user community of upcoming changes and the implications of those changes; the need for training of coders and data users; development of analytical methods and conduct of comparability studies; processes to test, accept and implement new or updated coding software; assessment of coding quality; changes to data analyses and reporting processes; updates to regular publications; and assessing the resources required for successful implementation.

11:59

At first glance, the gallery seems to be empty. Upon entering however, 11:59 reveals itself to be masking tape placed lackadaisically in seemingly geometric forms. Enter the gallery at 11:59 and you would witness the light and shadows correlate with the gestural marks that have been made. Exploring ideas of time, space, gesture, value and mark-making, this work can be interpreted to be overflowing with confidence and/or impotence. It whispers about site and encounters, over-complication and simplicity, and boldness and hesitancy.

The association between maternal infant feeding practices and child weight at 11-17 months in first-time Australian mothers

Introduction: Emerging evidence reveals that early feeding practices are associated with child food intake, eating behaviour and weight status. This cross-sectional analysis examined the association between maternal infant feeding practices/beliefs and child weight in Australian infants aged 11-17 months. Methods: Participants were 293 first-time mothers of healthy term infants (144 boys, mean age 14±1 months) enrolled in the NOURISH RCT. Mothers self-reported infant feeding practices and beliefs using the Infant Feeding Questionnaire (Baughcum, 2001). Anthropometric data were also measured at baseline (infants aged 4 months). Multiple regression analysis was used, adjusting for infant age, gender, birth weight, infant feeding mode (breast vs. formula), maternal perceptions of infant weight status, pre-pregnancy weight, weight concern, age and education. Results: The average child weight-for-age z-score (WAZ) was 0.62±0.83 (range:-1.56 to 2.94) and the mean change in WAZ (WAZ change) from 4 to 14 months was 0.62±0.69 (range:-1.50 to 2.76). Feeding practices/beliefs partly explained child WAZ (R2=0.28) and WAZ change (R2=0.13) in the adjusted models. While child weight status at 14 months was inversely associated with responsive feeding (e.g. baby feeds whenever she wants, feeding to stop baby being unsettled) (β=-0.104, p=0.06) and maternal concern about the child becoming underweight (β=-0.224, p<0.001), it was positively associated with mother’s concern about child overweight (β=0.197, p<0.05). Birth weight, infant’s age, maternal weight concern and perceiving her child as overweight were significant covariates. WAZ change was only significantly associated with responsive feeding (β=-0.147, p<0.05). Conclusion: Responsive feeding may be an important strategy to promote healthy child weight.

Expression Pattern of the Alpha-Kafirin Promoter Coupled with a Signal Peptide from Sorghum bicolor L. Moench

Regulatory sequences with endosperm specificity are essential for foreign gene expression in the desired tissue for both grain quality improvement and molecular pharming. In this study, promoters of seed storage α-kafirin genes coupled with signal sequence (ss) were isolated from Sorghum bicolor L. Moench genomic DNA by PCR. The α-kafirin promoter (α-kaf) contains endosperm specificity-determining motifs, prolamin-box, the O2-box 1, CATC, and TATA boxes required for α-kafirin gene expression in sorghum seeds. The constructs pMB-Ubi-gfp and pMB-kaf-gfp were microprojectile bombarded into various sorghum and sweet corn explants. GFP expression was detected on all explants using the Ubi promoter but only in seeds for the α-kaf promoter. This shows that the α-kaf promoter isolated was functional and demonstrated seed-specific GFP expression. The constructs pMB-Ubi-ss-gfp and pMB-kaf-ss-gfp were also bombarded into the same explants. Detection of GFP expression showed that the signal peptide (SP)::GFP fusion can assemble and fold properly, preserving the fluorescent properties of GFP.

Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages

Syntaxin 11 (Stx11) is a SNARE protein enriched in cells of the immune system. Loss or mutation of Stx11 results in familial hemophagocytic lymphohistiocytosis type-4 (FHL-4), an autosomal recessive disorder of immune dysregulation characterized by high levels of inflammatory cytokines along with defects in T-cell and natural killer cell function. We show here Stx11 is located on endosomalmembranes including late endosomes and lysosomes in macrophages. While Stx11 did not form a typical trans-SNARE complex, it did bind to the Q-SNARE Vti1b and was able to regulate the availability of Vti1b to form the Q-SNARE complexes Stx6/Stx7/Vtib and Stx7/Stx8/Vti1b. The mutant form of Stx11 sequestered Vti1b from forming the Q-SNARE complex that mediates late endosome to lysosome fusion. Depletion of Stx11 in activated macrophages leads to an accumulation of enlarged late endocytic compartments, increased trafficking to the cell surface and inhibition of late endosome to lysosome fusion. These phenotypes arerescued by the expression of an siRNA-resistant Stx11 construct in Stx11-depleted cells. Our results suggest that by regulating the availability of Vti1b, Stx11 regulates trafficking steps between late endosomes, lysosomes and the cell surface in macrophages.

Children physical activity correlates and parent physical activity do not have a strong association with physical activity amongst adolescents

Background: Physical activity is a key modifiable behavior impacting a number of important health outcomes. The path to developing chronic diseases commonly commences with lifestyle patterns developed during childhood and adolescence. This study examined whether parent physical activity and other factors correlated with physical activity amongst children are associated with self-reported physical activity in adolescents. Methods: A total of 115 adolescents (aged 12-14) and their parents completed questionnaire assessments. Self-reported physical activity was measured amongst adolescents and their parents using the International Physical Activity Questionnaire for Adolescents (IPAQ-A), and the International Physical Activity Questionnaire (IPAQ) respectively. Adolescents also completed the Children’s Physical Activity Correlates (CPAC), which measured factors that have previously demonstrated association with physical activity amongst children. To examine whether parent physical activity or items from the CPAC were associated with self-reported adolescent physical activity, backward step-wise regression was undertaken. One item was removed at each step in descending order of significance (until two tailed item alpha=0.05 was achieved). Results: A total of 93 (80.9%) adolescents and their parents had complete data sets and were included in the analysis. Independent variables were removed in the order: perceptions of parental role modeling; importance of exercise; perceptions of parental encouragement; peer acceptance; fun of physical exertion; perceived competence; parent physical activity; self-esteem; liking of exercise; and parental influence. The only variable remaining in the model was ‘liking of games and sport’ (p=0.003, adjusted r-squared=0.085). Discussion: These findings indicate that factors associated with self-reported physical activity in adolescents are not necessarily the same as younger children (aged 8-11). While ‘liking of games and sport’ was included in the final model, the r-squared value did not indicate a strong association. Interestingly, parent self-reported physical activity was not included in the final model. It is likely that adolescent physical activity may be influenced by a variety of direct and indirect forms of socialization. These findings do support the view that intrinsically motivated themes such as the liking of games and sport take precedence over outside influences, like those presented by parents, in determining youth physical activity behaviors. These findings do not suggest that parents have no influence on adolescent physical activity patterns, but rather, the influence is likely to be more complex than physical activity behavior modeling perceived by the adolescent. Further research in this field is warranted in order to better understand potential contributors to successful physical activity promotion interventions amongst young adolescents.

Eliciting metacognitive experiences and reflection in a year 11 chemistry classroom : an activity theory perspective

Concerns regarding students' learning and reasoning in chemistry classrooms are well documented. Students' reasoning in chemistry should be characterized by conscious consideration of chemical phenomenon from laboratory work at macroscopic, molecular/sub-micro and symbolic levels. Further, students should develop metacognition in relation to such ways of reasoning about chemistry phenomena. Classroom change eliciting metacognitive experiences and metacognitive reflection is necessary to shift entrenched views of teaching and learning in students. In this study, Activity Theory is used as the framework for intepreting changes to the rules/customs and tools of the activity systems of two different classes of students taught by the same teacher, Frances, who was teaching chemical equilibrium to those classes in consecutive years. An interpretive methodolgy involving multiple data sources was employed. Frances explicitly changed her pedagogy in the second year to direct students attention to increasingly consider chemical phenomena at the molecular/sub-micro level. Additonally, she asked students not to use the textbook until toward the end of the equilibrium unit and sought to engage them in using their prior knowledge of chemistry to understand their observations from experiments. Frances' changed pedagogy elicited metacognitive experiences and reflection in students and challenged them to reconsider their metacognitive beliefs about learning chemistry and how it might be achieved. While teacher change is essential for science education reform, students are not passive players in the change efforts and they need to be convinced of the viability of teacher pedagogical change in the context of their goals, intentions, and beliefs.

Criminology, Crime and Politics Before and After 9/11

Criminologists have mostly followed the criminal law in adopting an apolitical concept of crime. They paid limited attention to both political crime and the political power to criminalise. The article traces efforts to redress this since the 1960s. It nevertheless remained a minority concern, mostly of critical criminology. Yet crime has been politicised in various ways by other developments, also examined in the article. The events of 9/11 have crowned the emergence of crime as a strategic security issue posing a challenge to criminology to engage with politically inspired crime and its control.

Tolerance, Freedom, Justice and Peace?: Britain, Australia and anti-Muslim Racism in the UK and Australia before 11 September 2001

Since 11 September 2001, Muslim minorities have experienced intensive "othering" in “Western” countries, above all in those US-led anglophone nations which invaded Afghanistan and Iraq to prosecute their "war on terror". This paper examines the cases of Britain and Australia, where whole communities of Muslims have been criminalised as "evil" and a "fifth column" enemy within by media, politicians, the security services and the criminal justice system. Although constituted by disparate ethnic groups, the targeted communities in each of these nations have experienced similar treatment in the State's anti-terrorist measures, as well as ideological responses and everyday racism, making comparable the two cases.

Climates of Hate: Media and State Inspired Victimisation of Muslims in Canada and Australia since 9/11

This article represents a preliminary comparative exploration of anti-Muslim racism and violence in Australia and Canada, especially since September 11. We contextualise the anti-Muslim vilification and victimisation within parallel – yet still distinct – political climates that bestow permission to hate. That is, negative media portrayals, together with discriminatory rhetoric, policy and practices at the level of the state create an enabling environment that signals the legitimacy of public hostility toward the Muslim communities. We conclude by pointing toward the need for more extensive empirical exploration of the phenomenon in both countries.

Driver sleepiness self-regulation : physiological and subjective evidence

Introduction: Sleepiness contributes to a substantial proportion of fatal and severe road crashes. Efforts to reduce the incidence of sleep-related crashes have largely focussed on driver education to promote self-regulation of driving behaviour. However, effective self-regulation requires accurate self-perception of sleepiness. The aim of this study was to assess capacity to accurately identify sleepiness, and self-regulate driving cessation, during a validated driving simulator task. Methods: Participants comprised 26 young adult drivers (20-28 years) who had open licenses. No other exclusion criteria where used. Participants were partially sleep deprived (05:00 wake up) and completed a laboratory-based hazard perception driving simulation, counterbalanced to either at mid-morning or mid-afternoon. Established physiological measures (i.e., EEG, EOG) and subjective measures (Karolinska Sleepiness Scale), previously found sensitive to changes in sleepiness levels, were utilised. Participants were instructed to ‘drive’ on the simulator until they believed that sleepiness had impaired their ability to drive safely. They were then offered a nap opportunity. Results: The mean duration of the drive before cessation was 36.1 minutes (±17.7 minutes). Subjective sleepiness increased significantly from the beginning (KSS=6.6±0.7) to the end (KSS=8.2±0.5) of the driving period. No significant differences were found for EEG spectral power measures of sleepiness (i.e., theta or alpha spectral power) from the start of the driving task to the point of cessation of driving. During the nap opportunity, 88% of the participants (23/26) were able to reach sleep onset with an average latency of 9.9 minutes (±7.5 minutes). The average nap duration was 15.1 minutes (±8.1 minutes). Sleep architecture during the nap was predominately comprised of Stages I and II (combined 92%). Discussion: Participants reported high levels of sleepiness during daytime driving after very moderate sleep restriction. They were able to report increasing sleepiness during the test period despite no observed change in standard physiological indices of sleepiness. This increased subjective sleepiness had behavioural validity as the participants had high ‘napability’ at the point of driving cessation, with most achieving some degree of subsequent sleep. This study suggests that the nature of a safety instruction (i.e. how to view sleepiness) can be a determinant of driver behaviour.

Expression of HPV-11 L1 protein in transgenic Arabidopsis thaliana and Nicotiana tabacum

Background We have investigated the possibility and feasibility of producing the HPV-11 L1 major capsid protein in transgenic Arabidopsis thaliana ecotype Columbia and Nicotiana tabacum cv. Xanthi as potential sources for an inexpensive subunit vaccine. Results Transformation of plants was only achieved with the HPV-11 L1 gene with the C-terminal nuclear localization signal (NLS-) encoding region removed, and not with the full-length gene. The HPV-11 L1 NLS- gene was stably integrated and inherited through several generations of transgenic plants. Plant-derived HPV-11 L1 protein was capable of assembling into virus-like particles (VLPs), although resulting particles displayed a pleomorphic phenotype. Neutralising monoclonal antibodies binding both surface-linear and conformation-specific epitopes bound the A. thaliana-derived particles and - to a lesser degree - the N. tabacum-derived particles, suggesting that plant-derived and insect cell-derived VLPs displayed similar antigenic properties. Yields of up to 12 μg/g of HPV-11 L1 NLS- protein were harvested from transgenic A. thaliana plants, and 2 μg/g from N. tabacum plants - a significant increase over previous efforts. Immunization of New Zealand white rabbits with ∼50 μg of plant-derived HPV-11 L1 NLS- protein induced an antibody response that predominantly recognized insect cell-produced HPV-11 L1 NLS- and not NLS+ VLPs. Evaluation of the same sera concluded that none of them were able to neutralise pseudovirion in vitro. Conclusion We expressed the wild-type HPV-11 L1 NLS- gene in two different plant species and increased yields of HPV-11 L1 protein by between 500 and 1000-fold compared to previous reports. Inoculation of rabbits with extracts from both plant types resulted in a weak immune response, and antisera neither reacted with native HPV-11 L1 VLPs, nor did they neutralise HPV-11 pseudovirion infectivity. This has important and potentially negative implications for the production of HPV-11 vaccines in plants. © 2007 Kohl et al; licensee BioMed Central Ltd.