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Biomedical subjects

V Kay

Publications and source records attributed to V Kay.

5 recordsLinked to original sources

Scaffold/matrix-attached regions: structural properties creating transcriptionally active loci.

The expression characteristics of the human interferon-beta gene, as part of a long stretch of genomic DNA, led to the discovery of the putative domain bordering elements. The chromatin structure of these elements and their surroundings was determined during the process of gene activation and correlated with their postulated functions. It is shown that these "scaffold-attached regions" (S/MAR elements) have some characteristics in common with and others distinct from enhancers with which they cooperate in various ways. Our model of S/MAR function will focus on their properties of mediating topological changes within the respective domain.

Base Sequence

A plant scaffold attached region detected close to a T-DNA integration site is active in mammalian cells.

Integration of foreign genes into plant genomes by the Agrobacterium T-DNA transfer system has been considered to occur at random. It has been speculated that the chromosomal structure of the integration site might affect the expression pattern of the introduced genes. To gain insight into the molecular structure of T-DNA integration sites and its possible impact on gene expression, we have examined plant DNA sequences in the vicinity of T-DNA borders. Analysis of a transgenic petunia plant containing a chloramphenicol acetyltransferase (CAT) gene regulated by the hemoglobin promoter (PAR) from Parasponia andersonii revealed a scaffold attachment region (SAR) close to one T-DNA end. In addition to having strong binding affinities for both animal and plant nuclear scaffolds this petunia SAR element is as active in mammalian cells as the authentic elements from mammalian sources.

Agrobacterium tumefaciens

Binding specificity of a nuclear scaffold: supercoiled, single-stranded, and scaffold-attached-region DNA.

Scaffold-attached-region (SAR) elements of DNA enhance transcriptional rates, and this has been correlated with their ability to undergo separation into single strands (ssDNA) under conditions of negative superhelicity (Bode et al., 1992). The competition studies presented here suggest that the SAR-scaffold interaction is based, in part, on the recognition of single strands, while about one-half of SAR sites are inaccessible to ssDNA. Conversely, since there are 20,000 SAR sites but more than 60,000 sites for ssDNA per nuclear equivalent, not all ssDNA sites are open for SARs. In addition, a completely separate set of binding centers recognizing and enzymatically converting DNA of superhelical density below -0.04 can be titrated. These findings reflect multiple binding specificities for scaffold preparations that are routinely used for screening scaffold-attached regions.

Animals

Skeletal hyperostosis and extraosseous calcification in patients receiving long-term etretinate (Tigason).

In an ongoing study of patients on long-term etretinate (Tigason) therapy, 13 patients with a congenital or inherited disorder of keratinization and 10 patients with psoriasis were examined to investigate the incidence of, and the factors associated with, skeletal hyperostosis. Skeletal scintigraphy, plain radiographs, haematological and biochemical analyses were performed. Using all criteria, 7 of 13 patients with a congenital or inherited disorder of keratinization showed evidence of hyperostosis. No single investigation was able to detect all these cases; in particular, skeletal scintigraphy was positive in only nine of the 13 patients who showed hyperostosis. Eleven of the 13 patients with hyperostosis gave a history of musculoskeletal symptoms compared with three of the 10 patients without hyperostosis. There was no clear association with total dose or duration of treatment. Serum chemistry and haematological studies were normal. In two patients the 24-h urinary calcium excretion was significantly elevated, an abnormality which has not been described previously. Annual lateral thoracic spine radiographs with additional views of symptomatic areas are recommended for patients on long-term etretinate therapy.

Adult

Laterality effects for tactile patterns.

A series of studies was carried out to investigate laterality effects in the discrimination of tactile patterns presented to the fingertips of right-handed subjects. When both hands were stimulated simultaneously, a small right-hand advantage (RHA) was observed for a sequential task and a small left-hand advantage (LHA) was found for a spatial task, but only in women and only when there was a delay or mask between presentation and response. This may indicate different attentional strategies for men and women, or better shielding against interhemispheric interference in women. When only one hand was stimulated at a time (unimanual tasks), no laterality effects were found with sequential tasks, but a substantial RHA for a spatial task was observed. Because the unimanual spatial task involves more possible alternatives than the unimanual sequential ones, this RHA may be a consequence of increased information load rather than a the spatial/sequential distinction. While laterality effects in tactile laterality studies are relatively inconsistent, there are clear differences between bimanual and unimanual presentation. Effects related to hemispheric specialization are much more evident with bilateral presentation.

Female