Genetic and Non-genetic Predictors of LINE-1 Methylation in Leukocyte DNA.

Background: Altered DNA methylation has been associated with various diseases. Objective: We evaluated the association between levels of methylation in leukocyte DNA at long interspersed nuclear element 1 (LINE-1) and genetic and non-genetic characteristics of 892 control participants from the Spanish Bladder Cancer/EPICURO study. Methods: We determined LINE-1 methylation levels by pyrosequencing. Individual data included demographics, smoking status, nutrient intake, toenail concentrations of 12 trace elements, xenobiotic metabolism gene variants, and 515 polymorphisms among 24 genes in the one-carbon metabolism pathway. To assess the association between LINE-1 methylation levels (percentage of methylated cytosines) and potential determinants, we estimated beta coefficients (βs) by robust linear regression. Results: Women had lower levels of LINE-1 methylation than men (β = –0.7, p = 0.02). Persons who smoked blond tobacco showed lower methylation than nonsmokers (β = –0.7, p = 0.03). Arsenic toenail concentration was inversely associated with LINE-1 methylation (β = –3.6, p = 0.003). By contrast, iron (β = 0.002, p = 0.009) and nickel (β = 0.02, p = 0.004) were positively associated with LINE-1 methylation. Single nucleotide polymorphisms (SNPs) in DNMT3A (rs7581217-per allele, β = 0.3, p = 0.002), TCN2 (rs9606756-GG, β = 1.9, p = 0.008; rs4820887-AA, β = 4.0, p = 4.8 × 10–7; rs9621049-TT, β = 4.2, p = 4.7 × 10–9), AS3MT (rs7085104-GG, β = 0.7, p = 0.001), SLC19A1 (rs914238, TC vs. TT: β = 0.5 and CC vs. TT: β = –0.3, global p = 0.0007) and MTHFS (rs1380642, CT vs. CC: β = 0.3 and TT vs. CC; β = –0.8, global p = 0.05) were associated with LINE-1 methylation. Conclusions: We identified several characteristics, environmental factors, and common genetic variants that predicted DNA methylation among study participants.This work was partially supported by the Association for International Cancer Research (AICR; grant 09-0780, and a doctoral scholarship awarded to S.M.T.); Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, MINECO, Spain (grants 00/0745, PI051436, PI061614, PI09-02102, and G03/174); Red Temática de Investigación Cooperativa en Cáncer (grant RD06/0020-RTICC); the U.S. National Institutes of Health (grant RO1-CA089715); a postdoctoral fellowship awarded to A.F.S.A. from the Fundación Científica de la AECC; Fundació Marató TV3; and The Johns Hopkins University Vredenburg Scholarship awarded to A.L.C

Detection of Apparent Early Rabies Infection by LN34 Pan-Lyssavirus Real-Time RT-PCR Assay in Pennsylvania

The Pennsylvania Department of Health Bureau of Laboratories (PABOL) tested 6855 animal samples for rabies using both the direct fluorescent antibody test (DFA) and LN34 pan-lyssavirus reverse transcriptase quantitative PCR (RT-qPCR) during 2017–2019. Only two samples (0.03%) were initially DFA negative but positive by LN34 RT-qPCR. Both cases were confirmed positive upon re-testing at PABOL and confirmatory testing at the Centers for Disease Control and Prevention by LN34 RT-qPCR and DFA. Rabies virus sequences from one sample were distinct from all positive samples processed at PABOL within two weeks, ruling out cross-contamination. Levels of rabies virus antigen and RNA were low in all brain structures tested, but were higher in brain stem and rostral spinal cord than in cerebellum, hippocampus or cortex. Taken together, the low level of rabies virus combined with higher abundance in more caudal brain structures suggest early infection. These cases highlight the increased sensitivity and ease of interpretation of LN34 RT-qPCR for low positive cases

Integrating nowcasting with crisis management and risk prevention in a transnational and interdisciplinary framework

This paper presents the recent WWRP/WMO Forecast Demonstration Project INCA-CE (INtegrating nowCAsting for Central Europe) co-funded by the European Union. Twenty-four partners of national and regional hydro-meteorological services, national and regional crisis and disaster management centers, and authorities for road management world-wide have participated in INCA-CE for international cooperation on nowcasting development, interdisciplinary cooperation for nowcasting applications and transnational cooperation for nowcasting services. INCA-CE has implemented the nowcasting system INCA at the project partner countries, applied INCA nowcasting in civil protection, operational hydrology and road safety, and improved the INCA system based on the end user's requirements. The main difference to other similar projects is that end user's involvement and the improvements involve the whole end user value chain. The project has developed several ideas for end users on how to interpret nowcasting products (INCA-SWING) and on how to deal with the nowcasting products in their working practice (INCA-MCPEX and ISW). INCA-CE is also oriented strongly to transnational cooperation in nowcasting development and implementation, in easy access to a homogenized set of nowcasting products from those INCA providers to end users in the region, and in the transnational use of real-time products by end users in cases of high impact weather across borders