TIGER : The gene expression regulatory variation landscape of human pancreatic islets

Genome-wide association studies (GWASs) identified hundreds of signals associated with type 2 diabetes (T2D). To gain insight into their underlying molecular mechanisms, we have created the translational human pancreatic islet genotype tissue-expression resource (TIGER), aggregating >500 human islet genomic datasets from five cohorts in the Horizon 2020 consortium T2DSystems. We impute genotypes using four reference panels and meta-analyze cohorts to improve the coverage of expression quantitative trait loci (eQTL) and develop a method to combine allele-specific expression across samples (cASE). We identify >1 million islet eQTLs, 53 of which colocalize with T2D signals. Among them, a low-frequency allele that reduces T2D risk by half increases CCND2 expression. We identify eight cASE colocalizations, among which we found a T2D-associated SLC30A8 variant. We make all data available through the TIGER portal (http://tiger.bsc.es), which represents a comprehensive human islet genomic data resource to elucidate how genetic variation affects islet function and translates into therapeutic insight and precision medicine for T2D.Peer reviewe

An Immunoassay for Dibutyl Phthalate Based on Direct Hapten Linkage to the Polystyrene Surface of Microtiter Plates

BACKGROUND: Dibutyl phthalate (DBP) is predominantly used as a plasticizer inplastics to make them flexible. Extensive use of phthalates in both industrial processes and other consumer products has resulted in the ubiquitous presence of phthalates in the environment. In order to better determine the level of pollution in the environment and evaluate the potential adverse effects of exposure to DBP, immunoassay for DBP was developed. METHODOLOGY/PRINCIPAL FINDINGS: A monoclonal antibody specific to DBP was produced from a stable hybridoma cell line generated by lymphocyte hybridoma technique. An indirect competitive enzyme-linked immunosorbent assay (icELISA) employing direct coating of hapten on polystyrene microtiter plates was established for the detection of DBP. Polystyrene surface was first oxidized by permanganate in dilute sulfuric acid to generate carboxyl groups. Then dibutyl 4-aminophthalate, which is an analogue of DBP, was covalently linked to the carboxyl groups of polystyrene surface with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC). Compared with conjugate coated format (IC(50)=106 ng/mL), the direct hapten coated format (IC(50)=14.6 ng/mL) improved assay sensitivity after careful optimization of assay conditions. The average recovery of DBP from spiked water sample was 104.4% and the average coefficient of variation was 9.95%. Good agreement of the results obtained by the hapten coated icELISA and gas chromatography-mass spectrometry further confirmed the reliability and accuracy of the icELISA for the detection of DBP in certain plastic and cosmetic samples. CONCLUSIONS/SIGNIFICANCE: The stable and efficient hybridoma cell line obtained is an unlimited source of sensitive and specific antibody to DBP. The hapten coated format is proposed as generally applicable because the carboxyl groups on modified microtiter plate surface enables stable immobilization of aminated or hydroxylated hapten with EDC. The developed hapten coated icELISA can be used as a convenient quantitative tool for the sensitive and accurate monitoring DBP in water, plastic and cosmetic samples

Sensitivity and efficacy of the succinate dehydrogenase inhibitor fluxapyroxad, against raspberry spur blight fungus Didymella applanata

Didymella applanata, the causal agent of raspberry spur blight, is a destructive plant pathogen that can cause serious reductions in total yield. The use of fungicides plays a crucial role in successful control of the pathogen. The sensitivity of 94 isolates (66 collected during 2013 and 28 in 2017) of D. applanata to the succinate dehydrogenase inhibitor, fluxapyroxad, was evaluated in this study. In addition, the efficacy of fluxapyroxad in raspberry spur blight control in the field was determined. The isolates tested in this study showed different sensitivity to fluxapyroxad in vitro. The EC50 values of total number of isolates tested were ranged from 0.82 to 5.92 mu gml(-1). The ranges of EC50 values for the isolates varied between the localities where the isolates originated from and also the year of isolation. The mean EC50 values in the group of isolates obtained in 2013 were 1.95 mu gml(-1)+/- 0.81 (0.82 to 4.05 mu gml(-1)), while the EC50 values for those isolated in 2017 were ranged from 1.16 to 5.78 mu gml(-1) (mean=3.24 mu gml(-1)+/- 1.38). The efficacy trials were conducted during 2017 and 2018 in a commercial raspberry field at two locations in western part of Serbia. Applied in both concentration rates 0.02 and 0.03% of the formulated product (0.006 and 0.009% of a.i.), fluxapyroxad showed a very high efficacy in spur blight control in practical condition