Search PubMedSearch

Biomedical subjects

M J Hansen

Publications and source records attributed to M J Hansen.

9 recordsLinked to original sources

microphthalmia, a critical factor in melanocyte development, defines a discrete transcription factor family.

The microphthalmia (mi) gene appears essential for pigment cell development and/or survival, based on its mutation in mi mice. It has also been linked to the human disorder Waardenburg Syndrome. The mi gene was recently cloned and predicts a basic/helix-loop-helix/leucine zipper (b-HLH-ZIP) factor with tissue-restricted expression. Here, we show that Mi protein binds DNA as a homo- or heterodimer with TFEB, TFE3, or TFEC, together constituting a new MiT family. Mi can also activate transcription through recognition of the M box, a highly conserved pigmentation gene promoter element, and may thereby determine tissue-specific expression of pigmentation enzymes. Six mi mutations shown recently to cluster in the b-HLH-ZIP region produce surprising and instructive effects on DNA recognition and oligomerization. An alternatively spliced exon located outside of the b-HLH-ZIP region is shown to significantly modulate DNA recognition by the basic domain. These findings suggest that Mi's critical roles in melanocyte survival and pigmentation are mediated by MiT family interactions and transcriptional activities.

Alternative Splicing

The ompA 5' untranslated region impedes a major pathway for mRNA degradation in Escherichia coli.

The unusual longevity of the Escherichia coli ompA transcript is determined by its 5' untranslated region (UTR), which functions in vivo as an mRNA stabilizer. Here we show that this 5' UTR can prolong the lifetime in E. coli of a variety of heterologous mRNAs to which it is joined, either as a gene fusion or as an operon fusion. Statistical extrapolation suggests that it is quite likely that most E. coli mRNAs could be stabilized in this manner. We conclude that the ompA 5' UTR impedes a major pathway for mRNA degradation in E. coli and that stabilization by fusion to this UTR does not require translational readthrough of the heterologous mRNA segment by ribosomes that initiate translation at the ompA ribosome-binding site. Additional experiments indicate that the E. coli ribonuclease whose action is slowed by the ompA 5' UTR is not RNase III.

Bacterial Outer Membrane Proteins

Inadequacy of the WHO classification of the thyroid gland.

In order to evaluate the reproducibility of the WHO classification of goitre, the observer variation was estimated as kappa coefficients. Three observers independently inspected and palpated the thyroid gland of 53 patients twice and assessed the thyroid according to the five grades of the WHO classification. The thyroid volume was also measured by ultrasonography. We found kappa values from 0.15 to 0.70 in the interobserver study, and from 0.02 to 0.89 in the intraobserver study. Considerable overlap between the five grades was demonstrated when the assessments were related to volume estimated by ultrasonography. Description of the thyroid gland according to the WHO classification is inaccurate and not reproducible and is therefore of limited value.

Adult