50 research outputs found

    Smoking initiation is followed by the early acquisition of epigenetic change in cervical epithelium: a longitudinal study

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    background: To prove a causal link between an epigenetic change and an environmental or behavioural risk factor for a given disease, it is first necessary to show that the onset of exposure precedes the first detection of that epigenetic change in subjects who are still free of disease. methods: Towards this end, a cohort of women aged 15–19 years, recruited soon after they first had sexual intercourse, were used to provide sequential observations on the relationship between cigarette smoking and the detection in cervical cytological samples of methylated forms of CDKN2A (p16) using nested methylation-specific polymerase chain reaction. results: Among women who remained cytologically normal and who tested negative for human papillomavirus DNA in cervical smears during follow-up, those who first started to smoke during follow-up had an increased risk of acquiring CDKN2A methylation compared with never-smokers (odds ratio=3.67; 95% confidence interval 1.09–12.33; P=0.04). conclusion: Smoking initiation is associated with the appearance of methylated forms of CDKN2A

    Cell Cycle Gene Networks Are Associated with Melanoma Prognosis

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    BACKGROUND: Our understanding of the molecular pathways that underlie melanoma remains incomplete. Although several published microarray studies of clinical melanomas have provided valuable information, we found only limited concordance between these studies. Therefore, we took an in vitro functional genomics approach to understand melanoma molecular pathways. METHODOLOGY/PRINCIPAL FINDINGS: Affymetrix microarray data were generated from A375 melanoma cells treated in vitro with siRNAs against 45 transcription factors and signaling molecules. Analysis of this data using unsupervised hierarchical clustering and Bayesian gene networks identified proliferation-association RNA clusters, which were co-ordinately expressed across the A375 cells and also across melanomas from patients. The abundance in metastatic melanomas of these cellular proliferation clusters and their putative upstream regulators was significantly associated with patient prognosis. An 8-gene classifier derived from gene network hub genes correctly classified the prognosis of 23/26 metastatic melanoma patients in a cross-validation study. Unlike the RNA clusters associated with cellular proliferation described above, co-ordinately expressed RNA clusters associated with immune response were clearly identified across melanoma tumours from patients but not across the siRNA-treated A375 cells, in which immune responses are not active. Three uncharacterised genes, which the gene networks predicted to be upstream of apoptosis- or cellular proliferation-associated RNAs, were found to significantly alter apoptosis and cell number when over-expressed in vitro. CONCLUSIONS/SIGNIFICANCE: This analysis identified co-expression of RNAs that encode functionally-related proteins, in particular, proliferation-associated RNA clusters that are linked to melanoma patient prognosis. Our analysis suggests that A375 cells in vitro may be valid models in which to study the gene expression modules that underlie some melanoma biological processes (e.g., proliferation) but not others (e.g., immune response). The gene expression modules identified here, and the RNAs predicted by Bayesian network inference to be upstream of these modules, are potential prognostic biomarkers and drug targets

    Remote detection of invasive alien species

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    The spread of invasive alien species (IAS) is recognized as the most severe threat to biodiversity outside of climate change and anthropogenic habitat destruction. IAS negatively impact ecosystems, local economies, and residents. They are especially problematic because once established, they give rise to positive feedbacks, increasing the likelihood of further invasions and spread. The integration of remote sensing (RS) to the study of invasion, in addition to contributing to our understanding of invasion processes and impacts to biodiversity, has enabled managers to monitor invasions and predict the spread of IAS, thus supporting biodiversity conservation and management action. This chapter focuses on RS capabilities to detect and monitor invasive plant species across terrestrial, riparian, aquatic, and human-modified ecosystems. All of these environments have unique species assemblages and their own optimal methodology for effective detection and mapping, which we discuss in detail

    Appraisal of anti-smoking advertising by youth at risk for regular smoking : a comparative study in the United States, Australia, and Britain

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    We compare the similarity in how youth in the United States, Australia, and Britain appraise anti-smoking advertisements with different characteristics. Each participant viewed and evaluated a set of 10 anti-smoking adverts (from an overall total of 50 adverts) in a controlled experimental context using an audience response methodology. A structured telephone interview was completed one week after viewing the adverts, in which recall and engagement with the adverts by participants was evaluated. 615 youths who were experimenting with smoking or were susceptible nonsmokers. Measures of advert appraisal and engagement. Youth in the United States, Australia, and Britain responded in very similar ways to the same anti-smoking advertisements. In full multivariate models, the target audience of the advert and the advert theme were not related to the main outcome measures employed in this study. However, adverts with visceral negative or personal testimonial executional characteristics were appraised more positively by youths and were more likely to be recalled, thought about, and discussed at follow up one week later. Youths in three different countries responded to anti-smoking advertisements in very similar ways, suggesting that such adverts might be more actively shared among nations. The appraisal of, and engagement with, the anti-smoking adverts, however, varied substantially depending on executional characteristics. In the design of effective anti-smoking adverts, due attention needs to be paid to those characteristics that appear to most engage youth across different social and cultural environments
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