33 research outputs found
Determination of zearalenone and its metabolites in endometrial cancer by coupled separation techniques
This study presents a selective method of isolation of zearalenone (ZON) and its metabolite, α-zearalenol (α-ZOL), in neoplastically changed human tissue by accelerated solvent and ultrasonic extractions using a mixture of acetonitrile/water (84/16% v/v) as the extraction solvent. Extraction effectiveness was determined through the selection of parameters (composition of the solvent mixture, temperature, pressure, number of cycles) with tissue contamination at the level of nanograms per gram. The produced acetonitrile/water extracts were purified, and analytes were enriched in columns packed with homemade molecularly imprinted polymers. Purified extracts were determined by liquid chromatography (LC) coupled with different detection systems (diode array detection - DAD and mass spectrometry - MS) involving the Ascentis RP-Amide as a stationary phase and gradient elution. The combination of UE-MISPE-LC (ultrasonic extraction - molecularly imprinted solid-phase extraction - liquid chromatography) produced high (Râââ95â98%) and repeatable (RSDâ<â3%) recovery values for ZON and α-ZOL
Identification of a Novel Risk Locus for Multiple Sclerosis at 13q31.3 by a Pooled Genome-Wide Scan of 500,000 Single Nucleotide Polymorphisms
Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system with an important genetic component and strongest association driven by the HLA genes. We performed a pooling-based genome-wide association study of 500,000 SNPs in order to find new loci associated with the disease. After applying several criteria, 320 SNPs were selected from the microarrays and individually genotyped in a first and independent Spanish Caucasian replication cohort. The 8 most significant SNPs validated in this cohort were also genotyped in a second US Caucasian replication cohort for confirmation. The most significant association was obtained for SNP rs3129934, which neighbors the HLA-DRB/DQA loci and validates our pooling-based strategy. The second strongest association signal was found for SNP rs1327328, which resides in an unannotated region of chromosome 13 but is in linkage disequilibrium with nearby functional elements that may play important roles in disease susceptibility. This region of chromosome 13 has not been previously identified in MS linkage genome screens and represents a novel risk locus for the disease
Allele-Specific Gene Expression Is Widespread Across the Genome and Biological Processes
Allelic specific gene expression (ASGE) appears to be an important factor in human phenotypic variability and as a consequence, for the development of complex traits and diseases. In order to study ASGE across the human genome, we have performed a study in which genotyping was coupled with an analysis of ASGE by screening 11,500 SNPs using the Mapping 10 K Array to identify differential allelic expression. We found that from the 5,133 SNPs that were suitable for analysis (heterozygous in our sample and expressed in peripheral blood mononuclear cells), 2,934 (57%) SNPs had differential allelic expression. Such SNPs were equally distributed along human chromosomes and biological processes. We validated the presence or absence of ASGE in 18 out 20 SNPs (90%) randomly selected by real time PCR in 48 human subjects. In addition, we observed that SNPs close to -but not included in- segmental duplications had increased levels of ASGE. Finally, we found that transcripts of unknown function or non-coding RNAs, also display ASGE: from a total of 2,308 intronic SNPs, 1510 (65%) SNPs underwent differential allelic expression. In summary, ASGE is a widespread mechanism in the human genome whose regulation seems to be far more complex than expected
Tracking Chemical Processing Pathways in Combinatorial Polymer Libraries via Data Mining
Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2
The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality
Influence of initiator and different polymerisation conditions on performance of molecularly imprinted polymers
A set of polymers was imprinted with (â)-ephedrine using two different
initiators. A chemometrics approach was used to optimise experiments aimed at
analysis of the interplay of parameters such as polymerisation time, temperature
and percentage of initiator. The results presented demonstrate the importance of
keeping the right balance between these various parameters of polymerisation
conditions. It is shown that enhancing one single parameter such as polymer
rigidity does not necessarily improve polymer performance. In general it could
be concluded that MIPs should be synthesised over a long period of time using
low concentration of initiator and low temperature. The best selectivity was
achieved for polymers prepared by photo-initiation with 2,2-dimethoxy-2-
phenylacetophenone as initiat
The Ultratrace Determination of Fluoroquinolones in River Water Samples by an Online Solid-Phase Extraction Method Using a Molecularly Imprinted Polymer as a Selective Sorbent
Fluoroquinolones (FQs) are broad-spectrum antibiotics widely used to treat animal and human infections. The use of FQs in these activities has increased the presence of antibiotics in wastewater and food, triggering antimicrobial resistance, which has severe consequences for human health. The detection of antibiotics residues in water and food samples has attracted much attention. Herein, we report the development of a highly sensitive online solid-phase extraction methodology based on a selective molecularly imprinted polymer (MIP) and fluorescent detection (HPLC-FLD) for the determination of FQs in water at low ng L−1 level concentration. Under the optimal conditions, good linearity was obtained ranging from 0.7 to 666 ng L−1 for 7 FQs, achieving limits of detection (LOD) in the low ng L−1 level and excellent precision. Recoveries ranged between 54 and 118% (RSD < 17%) for all the FQs tested. The method was applied to determining FQs in river water. These results demonstrated that the developed method is highly sensitive and selective