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Julia Scheel

Publications and source records attributed to Julia Scheel.

3 recordsLinked to original sources

Variability of the human aryl hydrocarbon receptor nuclear translocator (ARNT) gene.

The aryl hydrocarbon receptor nuclear translocator (ARNT) plays an essential role in vertebrate transcriptional regulation as the common subunit of transcriptionally active complexes like the aryl hydrocarbon receptor (AHR)/ARNT heterodimer and hypoxia-inducible factor 1, mediating cellular responses to certain xenobiotics and to hypoxia, respectively. A cohort of healthy Caucasian volunteers was screened for genetic variations of ARNT. Six polymorphic sites could be identified, a variation in a G-stretch upstream of the ATG translation start site, a frequent silent mutation (G567C), two polymorphic sites in intron 9, and two single nucleotide substitutions leading to amino acid exchanges, G1531A (D511N) and T1551G (D517E). The frequencies were 0.005 for the Asn-coding allele and for the Glu-coding allele, respectively, with no linkage between these two mutations. Although no significant correlation with activities of CYP1A2, which is under regulatory control of the AHR/ARNT transcription complex, could be established, metabolic or pathological phenotypes may be associated with these variations.

Aryl Hydrocarbon Receptor Nuclear Translocator↗

Yellow pages to the transcriptome.

Transcriptomics has become an important tool for the large-scale analysis of biological processes. This review aims to provide sufficient criteria to make an appropriate choice among the variety of 'closed' systems, represented by DNA microarrays, and 'open' systems like fragment display, tag sequencing and subtractive hybridization, depending on the biological system under investigation. The most important technologies currently available are presented, their strengths and weaknesses are discussed and companies active in the field are listed. The potential of transcriptomics in the pharmaceutical research and development process is highlighted by applications in oncology, research on neurological diseases, and predictive toxicology. Finally, a prognosis for future developments of the technologies is given.

Animals↗

Transcriptomics in predictive toxicology.

Once again, genomics is about to change drug development. Following its major impact on target discovery and assay development, which increased the number of compounds at early stages of the process, genomics is now zeroing in on the prediction of potential toxicological problems of compounds. Toxicogenomics is the analysis of toxicological processes at the transcriptome level of a target organ or cell. By simultaneously monitoring the effect of a compound on the transcription levels of hundreds to thousands of genes, toxicogenomics can provide an enormous amount of data. This data bears information on the way in which compounds act at the molecular level, reaching far beyond the mere conclusion of whether or not a particular toxicological outcome is elicited. By compiling transcription profiles for well-known toxicants, we are beginning to learn how to analyze this novel type of data in the context of mechanistic and predictive toxicology.

Animals↗