Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma

Menstrual bleeding patterns: A community-based cross-sectional study among women aged 18-45 years in Southern Brazil

Abstract Background Population variation in the duration and amount of menstrual bleeding has received little attention in the literature. This study describes these characteristics and investigates the distribution of self-perceived amount of menstrual bleeding according to socio-demographic, behavioral, and reproductive characteristics. Methods A community-based cross-sectional study was conducted among 18-45 years old women users of the 31 primary health care (PHC) facilities in Pelotas city (Brazil). Interviews with structured questionnaire were carried out in the waiting rooms during two work shifts. Heaviness of menstrual bleeding was determined through the answer to the question: "Usually how much blood do you lose in every period?" Crude and adjusted analyses through Poisson regression took into account the aggregation per PHC facility. Results A total of 865 women were enrolled. Prevalence of heavy menstrual flow was 35.3% (95% CI 32.1-38.6%). In adjusted analyses, heavy menstrual bleeding was higher among the older, less educated and obese women, with higher number of pregnancies and who reported longer menstrual periods, extra-menstrual bleeding and clots in the flow. Use of hormonal contraceptive methods was protective against heavy menses. Conclusion Heavy menstrual bleeding is highly prevalent at the community level, and is associated with socio-demographic and anthropometric women's characteristics, as well as with duration of menstruation, extra-bleeding and presence of clots.</p

Evaluation of DNA Damage Induced by Environmental Exposure to Mercury in Liza aurata Using the Comet Assay

Mercury (Hg) is one of the major aquatic contaminants even though emissions have been reduced over the years. Despite the relative abundance of investigations carried out on Hg toxicity, there is a scarcity of studies on its DNA damaging effects in fish under realistic exposure conditions. This study assessed the Hg genotoxicity in Golden grey mullets (Liza aurata) at Laranjo basin, a particularly contaminated area of Ria de Aveiro (Portugal) well known for its Hg contamination gradient. (1) Fish were seasonally caught at Laranjo basin and at a reference site (S. Jacinto), and (2) animals from the reference site were transplanted and caged (at bottom and surface), for 3 days, in two different locations within Laranjo basin. Using the comet assay, blood was analyzed for genetic damage and apoptotic cell frequency. The seasonal survey showed greater DNA damage in the Hg-contaminated area for all sampling seasons excluding winter. The temporal variation pattern of DNA lesions was: summer ≈ autumn > winter > spring. Fish caged at Laranjo also exhibited greater DNA damage than those caged at the reference site, highlighting the importance of gill uptake on the toxicity of this metal. No increased susceptibility to apoptosis was detected in either wild or caged fish, indicating that mercury damages DNA of blood cells by a nonapoptotic mechanism. Both L. aurata and the comet assay proved to be sensitive and suitable for genotoxicity biomonitoring in mercury-contaminated coastal systems