Expression of GAD67 and Novel GAD67 Splice Variants During Human Fetal Pancreas Development: GAD67 Expression in the Fetal Pancreas

Glutamic acid decarboxylase (GAD) is a major inhibitory neurotransmitter in the brain, which catalyses the reaction of l-glutamate to γ-aminobutyric acid. There are two isoforms of GAD, a 65-kDa form and a 67-kDa form, which are encoded by two different genes. As previous studies suggested a role for GAD67 splice variants during fetal pancreas development, we have investigated the mRNA expression of GAD67 and GAD67 splice variants in a series of 14 human fetal pancreases between 14 weeks gestation and term and in adult control pancreases by RT-PCR. In this study, we demonstrate mRNA expression of GAD67 and four GAD67 splice variants, including GAD25, in human fetal and adult specimens. Some of the splice variants, including various proportions of exon 7 or a new exon between exons 6 and 7, have not been described before in the human pancreas. We speculate that the expression of these GAD67 splice variants might be related to human fetal pancreas development

Exposure assessment of process-related contaminants in food by biomarker monitoring

Exposure assessment is a fundamental part of the risk assessment paradigm, but can often present a number of challenges and uncertainties. This is especially the case for process contaminants formed during the processing, e.g. heating of food, since they are in part highly reactive and/or volatile, thus making exposure assessment by analysing contents in food unreliable. New approaches are therefore required to accurately assess consumer exposure and thus better inform the risk assessment. Such novel approaches may include the use of biomarkers, physiologically based kinetic (PBK) modelling-facilitated reverse dosimetry, and/or duplicate diet studies. This review focuses on the state of the art with respect to the use of biomarkers of exposure for the process contaminants acrylamide, 3-MCPD esters, glycidyl esters, furan and acrolein. From the overview presented, it becomes clear that the field of assessing human exposure to process-related contaminants in food by biomarker monitoring is promising and strongly developing. The current state of the art as well as the existing data gaps and challenges for the future were defined. They include (1) using PBK modelling and duplicate diet studies to establish, preferably in humans, correlations between external exposure and biomarkers; (2) elucidation of the possible endogenous formation of the process-related contaminants and the resulting biomarker levels; (3) the influence of inter-individual variations and how to include that in the biomarker-based exposure predictions; (4) the correction for confounding factors; (5) the value of the different biomarkers in relation to exposure scenario’s and risk assessment, and (6) the possibilities of novel methodologies. In spite of these challenges it can be concluded that biomarker-based exposure assessment provides a unique opportunity to more accurately assess consumer exposure to process-related contaminants in food and thus to better inform risk assessment

Genomewide Expression Analysis in Zebrafish mind bomb Alleles with Pancreas Defects of Different Severity Identifies Putative Notch Responsive Genes

10.1371/journal.pone.0001479PLoS ONE3

Correlation between the DNA methyltransferase (Dnmt) gene family and genome-wide 5-methylcytosine (5mC) in rotifer, copepod, and fish

DNA methyltransferases (DNMTs) are an enzyme family that catalyzes the transfer of a methyl group to DNA for a wide variety of biological functions. To determine whether the number and composition of the Dnmt gene family affects the 5-methylcytosine (5mc) ratio at the genome level, genome-wide 5mc ratios from three marine animals, the mangrove killifish (Kryptolebias marmoratus), an intertidal copepod (Tigriopus japonicus), and a monogonont rotifer (Brachionus koreanus), were analyzed in each organism after the cloning of Dnmt genes. Lineage- and teleost-specific gene evolution was observed in the vertebrate Dnmt3 gene family, while unique gene expansion was found in the T. japonicus Dnmt1 gene family. However, the rotifer did not have any apparent homologue of Dnmt1 or Dnmt3 in its genome. This gene information was highly supportive of genome-wide 5mc levels in the three marine animals. Therefore, the absence or presence of the Dnmt gene family could be an important evolutionary parameter of how this could affect genome-wide epigenetic metabolism