Publisher Correction: Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper

Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases

Trends for in situ and invasive melanoma in Queensland, Australia, 1982-2002

Objectives Queensland, the north-eastern state of Australia, has the highest incidence of melanoma in the world. Control measures started earlier here than probably anywhere else in the world; early detection programmes started in the 1960s and primary prevention in the 1980s. Data from the population-based Queensland Cancer Registry therefore provide an internationally unique data source with which to assess trends for in situ and invasive melanomas and to consider the implications for early detection and primary prevention. Methods We used Poisson regression to estimate the annual percentage change in rates across 21 years of incidence data for in situ and invasive lesions, stratified by age and sex. Joinpoint analyses were used to assess whether there had been a statistically significant change in the trends. Results In situ melanomas increased by 10.4% (95% CI: 10.1%, 11.1%) per year among males and 8.4% (7.9%, 8.9%) per year among females. The incidence of invasive lesions also increased, but not as quickly; males 2.6% (2.4%, 2.8%), females 1.2% (0.9%, 1.5%). Valid data on thickness was only available for 1991 to 2002 and for this period thin-invasive lesions were increasing faster than thick-invasive lesions (for example, among males: thin 3.8%, thick 2.0%). We found some suggestive evidence of lower proportionate increase for the most recent years for both in-situ and invasive lesions, but this did not achieve statistical significance. Among people younger than 35 years, the incidence of invasive melanoma was stable and there was a suggestion of a birth cohort effect from about 1958. Mortality rates were stable across all ages, and there was a suggestion of decreasing rates among young women, although this did not achieve statistical significance. Conclusion Age-standardised incidence is continuing to increase and this, in combination with a shift to proportionately more in situ lesions, suggests that the stabilisation of mortality rates is due, in large part, to earlier detection. For primary prevention, after a substantial period of sustained effort in Queensland, there is some suggestive, but not definitive, evidence that progress is being made. Incidence rates are stabilising in those younger than 35 years and the proportionate increase for both in situ and invasive lesions appears to be lower for the most recent period compared with previous periods. However, even taking the most favourable view of these trends, primary prevention is unlikely to lead to decreases in the overall incidence rate of melanoma for at least another 20 years. Consequently, the challenge for primary prevention programmes will be to maintain momentum over the long term. If this can be achieved, the eventual public-health benefits are likely to be substantial

Publisher Correction: Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.</jats:p