Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial.

Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients' response before treatment.

Functional characterization of a conducting polymer-based immunoassay system.

Experiments have been performed to characterize the electrical properties and functionality of a poly(3-hexylthiophene)-coated platinum electrode developed as a sensor for immunoassay read-out. Admittance measurements were performed on the coated electrodes as a function of frequency. The admittance spectra obtained show that the sensor is capacitive in nature. A circuit model is presented for comparison to other conducting polymer systems. Dynamic sensor response is characterized by oxidizing the polymer via a hydrogen peroxide-iodide pathway. Hydrogen peroxide is introduced either by direct injection or through a glucose-glucose oxidase reaction to determine electrode functionality and sensitivity. Sensor response to chemical oxidation is measured as a function of frequency and applied signal amplitude. System response is linear in frequency from 1 Hz to 70 Hz and in excitation amplitude up to approximately 600 mV. System sensitivity is analyzed based on oxidant generation from the enzyme-initiated pathway, sensor baseline drift, and the noise band on the quiescent sensor current.

Determination of atrazine in water by magnetic particle immunoassay: collaborative study.

A collaborative study was performed to determine mean recovery and precision for analysis of atrazine in drinking and surface waters by immunoassay. The study design was based on the blind duplicate test plan for collaborative studies. Three blank waters (municipal drinking water, well water, and surface water) were spiked at 3 atrazine levels. Two water samples with naturally incurred atrazine loads were also spiked with atrazine at 3 levels. In the enzyme-linked immunoassay method, the water sample is mixed with a pesticide-enzyme conjugate and added to paramagnetic particles with triazine-specific antibodies attached. After separation of antibody-bound atrazine and atrazine-enzyme conjugate from free components, the bound enzyme conjugate catalyzes a reaction producing a colored end product. The color developed is inversely proportional to the original concentration of atrazine in the water sample. Fourteen laboratories participated in the collaborative study. Data were analyzed for repeatability and reproducibility, and average recoveries at the spike levels were calculated. Over the concentration range tested, the mean recovery of atrazine spiked into blank and pesticide-contaminated waters was 104%. Overall RSDR averaged about 40% for atrazine concentrations near the method detection limit (0.05 microgram/L) and about 15% at concentrations above 5 times the detection limit (0.25 microgram/L). Corresponding single-analyst RSDr values were 24 and 10%. Recovery and precision for the 3 blank water matrixes and the waters that had been naturally contaminated with atrazine showed no significant differences. The magnetic particle immunoassay for determination of atrazine in water has been adopted first action by AOAC INTERNATIONAL.

Comparison of three bioassays for rat interferon.

Compared to the well-characterized murine and human interferons, few studies have been conducted on rat interferons. In the present study, we compared three rat interferon bioassays: a plaque-reduction method, a hemagglutination yield-reduction method, and a method involving reduction in viral cytopathic effect. These methods were evaluated in order to better assay rat interferons and thus facilitate investigations to determine the antiviral, antitumor, and immunoregulatory role of interferon in existing rat model systems. Each method has certain desirable characteristics; the choice of bioassay depends on the specific application required. Overall, the reduction in viral cytopathic effect bioassay combines most of the desired features of a rat interferon bioassay including sensitivity, precision, convenience, rapidity, and economy.