Het 'VELD'-project, addendum : uitwerking juli en augustus 2003

In een gebied van 3x3 km rond het dorp Vragender in de Achterhoek zijn uitgebreid metingen van ammoniakconcentraties (NH3) gedaan en emissies berekend aan de hand van in detail geregistreerde agrarische activiteiten. Op basis van deze emissies zijn modelberekeningen gedaan met het OPS-STe (korte termijn) verspreidingsmode

MicroRNAs as possible indicators of drug sensitivity in breast cancer cell lines

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. In this way they might influence whether a cell is sensitive or resistant to a certain drug. So far, only a limited number of relatively small scale studies comprising few cell lines and/or drugs have been performed. To obtain a broader view on miRNAs and their association with drug response, we investigated the expression levels of 411 miRNAs in relation to drug sensitivity in 36 breast cancer cell lines. For this purpose IC50 values of a drug screen involving 34 drugs were associated with miRNA expression data of the same breast cancer cell lines. Since molecular subtype of the breast cancer cell lines is considered a confounding factor in drug association studies, multivariate analysis taking subtype into account was performed on significant miRNA-drug associations which retained 13 associations. These associations consisted of 11 different miRNAs and eight different drugs (among which Paclitaxel, Docetaxel and Veliparib). The taxanes, Paclitaxel and Docetaxel, were the only drugs having miRNAs in common: hsa-miR-187-5p and hsa-miR-106a-3p indicative of drug resistance while Paclitaxel sensitivity alone associated with hsa-miR-556-5p. Tivantinib was associated with hsalet-7d-5p and hsa-miR-18a-5p for sensitivity and hsa-miR-637 for resistance. Drug sensitivity was associated with hsa-let-7a-5p for Bortezomib, hsa-miR-135a-3p for JNJ-707 and hsa-miR-185-3p for Panobinostat. Drug resistance was associated with hsa-miR-182-5p for Veliparib and hsa-miR-629-5p for Tipifarnib. Pathway analysis for significant miRNAs was performed to reveal biological roles, aiding to find a potential mechanistic link for the observed associations with drug response. By doing so hsa-miR-187-5p was linked to the cell cycle G2-M checkpoint in line with this checkpoint being the target of taxanes. In conclusion, our study shows that miRNAs could potentially serve as biomarkers for intrinsic drug resistance and that pathway analyses can provide additional information in this contex

MiRNA expression profiling of 51 human breast cancer cell lines reveals subtype and driver mutation-specific miRNAs

Introduction: Breast cancer is a genetically and phenotypically complex disease. To understand the role of miRNAs in this molecular complexity, we performed miRNA expression analysis in a cohort of molecularly well-characterized human breast cancer cell lines to identify miRNAs associated with the most common molecular subtypes and the most frequent genetic aberrations. Methods: Using a microarray carrying LNA™ modified oligonucleotide capture probes), expression levels of 725 human miRNAs were measured in 51 breast cancer cell lines. Differential miRNA expression was explored by unsupervised cluster analysis and was then associated with the molecular subtypes and genetic aberrations commonly present in breast cancer. Results: Unsupervised cluster analysis using the most variably expressed miRNAs divided the 51 breast cancer cell lines into a major and a minor cluster predominantly mirroring the luminal and basal intrinsic subdivision of breast cancer cell lines. One hundred and thirteen miRNAs were differentially expressed between these two main clusters. Forty miRNAs were differentially expressed between basal-like and normal-like/claudin-low cell lines. Within the luminal-group, 39 miRNAs were associated with ERBB2 overexpression and 24 with E-cadherin gene mutations, which are frequent in this subtype of breast cancer cell lines. In contrast, 31 miRNAs were associated with E-cadherin promoter hypermethylation, which, contrary to E-cadherin mutation, is exclusively observed in breast cancer cell lines that are not of luminal origin. Thirty miRNAs were associated with p16INK4 status while only a fe

Deficiency of TET3 leads to a genome-wide DNA hypermethylation episignature in human whole blood (vol 6, 92, 2021)

Genetics of disease, diagnosis and treatmen

Depositie van metalen van de atmosfeer in de Noordzee: modelberekeningen

De resultaten van een berekening van de jaargemiddelde atmosferische depositie van de spoorelementen As, Sb, Cd, Cu, Ni en Pb in de Noordzee worden gepresenteerd. Het model beschrijft de verspreiding in de atmosfeer dichtbij de bron met een Gaussische pluim en gaat voor grotere afstanden over in een doossector model met meerdere lagen in de verticaal. Droge en natte depositie worden beschreven als factor van de deeltjesgrootte en meteorologische variabelen. Emissies van alle Europese landen zijn in de berekening opgenomen. De berekende concentraties in het Noodzee-gebied zijn in het algemeen iets lager dan de overeenkomstige metingen op kustposities. Een verdere evaluatie vergt zowel betere emissieschattingen als betere metingen. De grootste bijdragen aan de depositie van bovenvermelde elementen is afkomstig van emissies van de landen aan de Noordzee: Verenigd Koninkrijk, Belgie, West-Duitsland, Frankrijk en Nederland.Abstract not availableDGMH/BWS-

Het 'VELD'-project, addendum : uitwerking juli en augustus 2003

In een gebied van 3x3 km rond het dorp Vragender in de Achterhoek zijn uitgebreid metingen van ammoniakconcentraties (NH3) gedaan en emissies berekend aan de hand van in detail geregistreerde agrarische activiteiten. Op basis van deze emissies zijn modelberekeningen gedaan met het OPS-STe (korte termijn) verspreidingsmode

The VELD experiment: An evaluation of the ammonia emissions and concentrations in an agricultural area

From July 2002until September 2003, a detailed ammonia emission inventory was carried out in concurrence with detailed measurements of the ammonia concentrations in air in a 3 × 3 km area in the East of the Netherlands. The main goal of the project was to validate the emission inventory by comparing modelled ammonia concentrations based on these emissions to the measured concentrations. It was found that the emissions from animal housings are the dominant source of ammonia over the year. Only incidentally, emissions of manure spreading were larger. The spatial and temporal variations in the concentrations over the year are well represented by the OPS model based on these emissions. For the entire period, the model shows an underestimation of the concentrations of about 15% (explained variance of the regression line of 76%). In the winter period, which is characterized by a dominance of the emissions from animal housings, the underestimation is only 5%. This most likely indicates that the emissions from animal housings, which in the area is mainly from pigs, are estimated correctly, as well as the modeling of the concentrations, for this period. In both the Spring and August 2003 period, a gap between calculated and measured ammonia concentrations was found. Under spring conditions, this gap is most likely the result of an underestimation of the emission during manure spreading. A part of the underestimation may be attributed to a reduction in the dry deposition process in the successive weeks after spreading which is caused by a saturation of the grassland with ammonium. Taking into account the uncertainty in this dry deposition process, it was estimated that the underestimate of the emissions by manure spreading could amount from 15% to 60%. The gap in August 2003, which was a very warm and dry month, is most probably caused by re-emission of ammonia at a large scale in and around the VELD area. The re-emission of ammonia from grass and crop land in August 2003 has a typical density of 14 g/ha/day during daytime. On a national scale this would mean for the Netherlands a re-emission of about 1 Gg during these three weeks of August