Reduction of low- and high-grade cervical abnormalities associated with high uptake of the HPV bivalent vaccine in Scotland

In Scotland, a national HPV immunisation programme began in 2008 for 12-13 year olds, with a catch-up campaign from 2008-2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established.  We analysed colposcopy data from a cohort of women born between 1988-1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012.  By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1) (RR 0.71, 95% CI 0.58 to 0.87, p=0.0008), CIN 2 (RR 0.5, 95% CI 0.4, 0.63, p<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58, p< 0.0001) for women who received 3 doses of vaccine compared with unvaccinated women.  To our knowledge, this is one of the first studies to show a reduction of low and high grade cervical intraepithelial neoplasia associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake

Cervical, Anal and Oral HPV in an Adolescent Inner-City Health Clinic Providing Free Vaccinations

Published human papillomavirus (HPV) vaccine trials indicate efficacy is strongest for those naive to the vaccine-types. However, few high-risk young women have been followed and cervical HPV has been the predominant outcome measure.We collected cervical and anal swabs, as well as oral rinse specimens from 645 sexually active inner-city young females attending a large adolescent health-clinic in New York City that offers free care and HPV vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type-specific prevalence of HPV at each anatomic site was compared for individuals by vaccination dose using generalized estimating equation logistic regression models.The majority of subjects reported being of non-Caucasian (92%) and/or Hispanic ethnicity (61%). Median age was 18 years (range:14-20). All had practiced vaginal sex, a third (33%) practiced anal sex, and most (77%) had also engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had received three doses. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in 7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types, the detection of HPV in the cervix of vaccinated compared to unvaccinated adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19, 95%CI:0.06-0.75), HPV16 (OR = 0.31, 95%CI:0.11-0.88) and HPV18 (OR = 0.14, 95%CI:0.03-0.75). For anal HPV, the risk of detecting vaccine types HPV6/11 (OR = 0.27, 95%CI:0.10-0.72) and HPV18(OR = 0.12, 95%CI:0.01-1.16) were significantly reduced for vaccinated adolescents however, the risk for HPV16 was not significantly decreased (OR = 0.63, 95%CI:0.18-2.20).HPV Prevalence is extremely high in inner-city female adolescents. Administration of the HPV vaccine reduced the risk for cervical HPV; however continued follow-up is required to assess the protection for HPV at all sites in young women with high exposure

SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation

Salmonella enterica is a prominent bacterial pathogen with implications on human and animal health. Salmonella serovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network for Salmonella at the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource for Salmonella. It comprehensively contains interactions between proteins encoded in Salmonella pathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides a Salmonella resource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available at http://salmonet.org

Methyl-donor depletion of head and neck cancer cells in vitro establishes a less aggressive tumour cell phenotype

PURPOSE: DNA methylation plays a fundamental role in the epigenetic control of carcinogenesis and is, in part, influenced by the availability of methyl donors obtained from the diet. In this study, we developed an in-vitro model to investigate whether methyl donor depletion affects the phenotype and gene expression in head and neck squamous cell carcinoma (HNSCC) cells. METHODS: HNSCC cell lines (UD-SCC2 and UPCI-SCC72) were cultured in medium deficient in methionine, folate, and choline or methyl donor complete medium. Cell doubling-time, proliferation, migration, and apoptosis were analysed. The effects of methyl donor depletion on enzymes controlling DNA methylation and the pro-apoptotic factors death-associated protein kinase-1 (DAPK1) and p53 upregulated modulator of apoptosis (PUMA) were examined by quantitative-PCR or immunoblotting. RESULTS: HNSCC cells cultured in methyl donor deplete conditions showed significantly increased cell doubling times, reduced cell proliferation, impaired cell migration, and a dose-dependent increase in apoptosis when compared to cells cultured in complete medium. Methyl donor depletion significantly increased the gene expression of DNMT3a and TET-1, an effect that was reversed upon methyl donor repletion in UD-SCC2 cells. In addition, expression of DAPK1 and PUMA was increased in UD-SCC2 cells cultured in methyl donor deplete compared to complete medium, possibly explaining the observed increase in apoptosis in these cells. CONCLUSION: Taken together, these data show that depleting HNSCC cells of methyl donors reduces the growth and mobility of HNSCC cells, while increasing rates of apoptosis, suggesting that a methyl donor depleted diet may significantly affect the growth of established HNSCC

Ion homeostasis in the Chloroplast

peer reviewedThe chloroplast is an organelle of high demand for macro- and micro-nutrient ions, which are required for the maintenance of the photosynthetic process. To avoid deficiency while preventing excess, homeostasis mechanisms must be tightly regulated. Here, we describe the needs for nutrient ions in the chloroplast and briefly highlight their functions in the chloroplastidial metabolism. We further discuss the impact of nutrient deficiency on chloroplasts and the acclimation mechanisms that evolved to preserve the photosynthetic apparatus. We finally present what is known about import and export mechanisms for these ions. Whenever possible, a comparison between cyanobacteria, algae and plants is provided to add an evolutionary perspective to the description of ion homeostasis mechanisms in photosynthesis