Drosophila fushi tarazu. a gene on the border of homeotic function.

BACKGROUND: Hox genes specify cell fate and regional identity during animal development. These genes are present in evolutionarily conserved clusters thought to have arisen by gene duplication and divergence. Most members of the Drosophila Hox complex (HOM-C) have homeotic functions. However, a small number of HOM-C genes, such as the segmentation gene fushi tarazu (ftz), have nonhomeotic functions. If these genes arose from a homeotic ancestor, their functional properties must have changed significantly during the evolution of modern Drosophila. RESULTS: Here, we have asked how Drosophila ftz evolved from an ancestral homeotic gene to obtain a novel function in segmentation. We expressed Ftz proteins at various developmental stages to assess their potential to regulate segmentation and to generate homeotic transformations. Drosophila Ftz protein has lost the inherent ability to mediate homeosis and functions exclusively in segmentation pathways. In contrast, Ftz from the primitive insect Tribolium (Tc-Ftz) has retained homeotic potential, generating homeotic transformations in larvae and adults and retaining the ability to repress homothorax, a hallmark of homeotic genes. Similarly, Schistocerca Ftz (Sg-Ftz) caused homeotic transformations of antenna toward leg. Primitive Ftz orthologs have moderate segmentation potential, reflected by weak interactions with the segmentation-specific cofactor Ftz-F1. Thus, Ftz orthologs represent evolutionary intermediates that have weak segmentation potential but retain the ability to act as homeotic genes. CONCLUSIONS: ftz evolved from an ancestral homeotic gene as a result of changes in both regulation of expression and specific alterations in the protein-coding region. Studies of ftz orthologs from primitive insects have provided a "snap-shot" view of the progressive evolution of a Hox protein as it took on segmentation function and lost homeotic potential. We propose that the specialization of Drosophila Ftz for segmentation resulted from loss and gain of specific domains that mediate interactions with distinct cofactors.

The nuclear receptor Ftz-F1 and homeodomain protein Ftz interact through evolutionarily conserved protein domains.

The Drosophila homeodomain protein Fushi Tarazu (Ftz) and its partner, the orphan receptor Ftz-F1, are members of two distinct families of DNA binding transcriptional regulators. Ftz and Ftz-F1 form a novel partnership in vivo as a Hox/orphan receptor heterodimer. Here we show that the murine Ftz-F1 ortholog SF-1 functionally substitutes for Ftz-F1 in vivo, rescuing the defects of ftz-f1 mutants. This finding identified evolutionarily conserved domains of Ftz-F1 as critical for activity of this receptor in vivo. These domains function, at least in part, by mediating direct protein interactions with Ftz. The Ftz-F1 DNA binding domain interacts strongly with Ftz and dramatically facilitates the binding of Ftz to target DNA. This interaction is augmented by a second interaction between the AF-2 domain of Ftz-F1 and the N-terminus of Ftz via an LRALL sequence in Ftz that is reminiscent of LXXLL motifs in nuclear receptor coactivators. We propose that Ftz-F1 serves as a cofactor for Ftz by facilitating the selection of target sites in the genome that contain Ftz/Ftz-F1 composite binding sites. Ftz, on the other hand, influences Ftz-F1 activity by interacting with its AF-2 domain in a manner that mimics a nuclear receptor coactivator.

Evaluation of five devices for self-monitoring of blood glucose in the normoglycaemic range.

Although hypoglycaemia is a serious risk of intensive insulin therapy, studies on the accuracy of devices for self-monitoring of blood glucose (SMBG) include only a few values below 100 mg/dl. This study evaluated five SMBG devices in the normal range of blood glucose. In three separate series, capillary blood was taken from 207, 214 and 49 healthy subjects and was analysed with the SMBG devices and a laboratory method. Mean (+/- standard deviation) blood glucose values were 86+/-13 mg/dl, 83+/-12 mg/dl and 90+/-16 in series 1-3. All measurements with SMBG devices differed significantly from the laboratory method. The relative deviation from the laboratory method was 5.5% (2.4-10.5%, median and interquartile range) for Accutrend, 7.1% (3.6-12.6%) for Precision QID, 7.5% (3.7-13.7%) for Accu-Chek III, 14.1% (6.2-22.2%) for Companion 2 and 15.2% (10.3-21.3%) for One Touch II (p < 0.05). In conclusion, this study shows important differences in the accuracy of five SMBG devices in the normoglycaemic range. Accutrend and--to a lesser degree--Accu-Chek III and Precision QID obtained better results and can be recommended for SMBG in patients treated with intensive insulin therapy.