Novel Antennapedia and Ultrabithorax trimeric complexes with TBP and Exd regulate transcription.

BACKGROUND: Hox proteins interact with DNA and many other proteins, co-factors, transcriptional factors, chromatin remodeling components, non-coding RNAs and even the extracellular matrix that assembles the Hox complexes. The number of interacting partners continues to grow with diverse components and more transcriptional factors than initially thought. Hox complexes present many activities, but their molecular mechanisms to modulate their target genes remain unsolved. RESULTS: In this paper we showed the protein-protein interaction of Antp with Ubx through the homeodomain using BiFC in Drosophila. Analysis of Antp-deletional mutants showed that AntpHD helixes 1 and 2 are required for the interaction with Ubx. Also, we found a novel interaction of Ubx with TBP, in which the PolyQ domain of TBP is required for the interaction. Moreover, we also detected the formation of two new trimeric complexes of Antp with Ubx, TBP and Exd using BiFC-FRET; these proteins, however, do not form a trimeric interaction with BIP2 or TFIIEß. The novel trimeric complexes reduced Antp transcriptional activity, indicating that they could confer specificity for repression. CONCLUSIONS: Our results increase the number of transcriptional factors in the Antp and Ubx interactomes that form two novel trimeric complexes with TBP and Exd. We also report a new Ubx interaction with TBP. These novel interactions provide important clues of the dynamics of Hox-interacting complexes involved in transcriptional regulation, contributing to better understand Hox function.

Trimeric complexes of Antp-TBP with TFIIEß or Exd modulate transcriptional activity.

BACKGROUND: Hox proteins finely coordinate antero-posterior axis during embryonic development and through their action specific target genes are expressed at the right time and space to determine the embryo body plan. As master transcriptional regulators, Hox proteins recognize DNA through the homeodomain (HD) and interact with a multitude of proteins, including general transcription factors and other cofactors. HD binding specificity increases by protein-protein interactions with a diversity of cofactors that outline the Hox interactome and determine the transcriptional landscape of the selected target genes. All these interactions clearly demonstrate Hox-driven transcriptional regulation, but its precise mechanism remains to be elucidated. RESULTS: Here we report Antennapedia (Antp) Hox protein-protein interaction with the TATA-binding protein (TBP) and the formation of novel trimeric complexes with TFIIEß and Extradenticle (Exd), as well as its participation in transcriptional regulation. Using Bimolecular Fluorescence Complementation (BiFC), we detected the interaction of Antp-TBP and, in combination with Förster Resonance Energy Transfer (BiFC-FRET), the formation of the trimeric complex with TFIIEß and Exd in living cells. Mutational analysis showed that Antp interacts with TBP through their N-terminal polyglutamine-stretches. The trimeric complexes of Antp-TBP with TFIIEß and Exd were validated using different Antp mutations to disrupt the trimeric complexes. Interestingly, the trimeric complex Antp-TBP-TFIIEß significantly increased the transcriptional activity of Antp, whereas Exd diminished its transactivation. CONCLUSIONS: Our findings provide important insights into the Antp interactome with the direct interaction of Antp with TBP and the two new trimeric complexes with TFIIEß and Exd. These novel interactions open the possibility to analyze promoter function and gene expression to measure transcription factor binding dynamics at target sites throughout the genome.

Tall Cell Carcinoma With Reversed Polarity of the Breast.

Tall cell carcinoma with reversed polarity (TCCRP) of the breast is a rare entity with low potential for malignancy that exhibits some morphological similarities to the tall cell variant of papillary thyroid carcinoma. Immunohistochemical and molecular studies help establish the mammary origin of this neoplasm. Here, we describe the case of a 63-year-old woman with a finding of a nodular lesion during a screening mammogram, whose morphological findings and immunohistochemical studies confirmed the diagnosis of papillary high cell carcinoma with the reverse polarity of the mammary gland.

Relationship of Body Mass Index and Footprint Morphology to the Actual Height of the Medial Longitudinal Arch of the Foot.

The medial longitudinal arch height of the foot is linked to individual characteristics such as sex and body mass index, and these characteristics have been shown to be associated with conditions such as flat feet. In this cross-sectional descriptive study, we examined the medial longitudinal arch morphology in an adult population to determine if there are differences related to sex and body mass index, and values were obtained for the foot posture index. Normalized anthropometric measurements and arch indices were calculated from footprints. Groups, defined by sex and body mass index, were compared, and the correlations between body mass index and the variables were determined. In the population studied (266 women and 177 men), significant differences between men and women for the foot posture index and normalized arch measurements were found. Analysis of the variables related to body mass index indicated there were significant differences in arch indices. Significant differences and positive correlations were also found between the arch index and body mass index for the left and right feet among the men and women studied. The results obtained allow us to reflect on and analyze whether the medial longitudinal arch morphology classification methods used in the clinical and research setting are adequate or whether the influence of factors such as body mass index can generate confusion.

Effectiveness of custom-made foot orthoses in patients with rheumatoid arthritis: a randomized controlled trial.

OBJECTIVE:: To determine the effect of custom-made foot orthoses versus placebo insoles on pain, disability, foot functionality, and quality of life. DESIGN:: Double-blinded randomized controlled trial. SETTING:: University Podiatric Clinical Area. SUBJECTS:: Patients with rheumatoid arthritis. INTERVENTIONS:: Patients were randomly assigned to either group A, which received custom-made foot orthoses, or group B, which received placebo, flat cushioning insoles, for three months. MAIN MEASURES:: The primary outcome was foot pain, measured by visual analog scale. Foot functionality, foot-related disability, and quality of life were measured using the Foot Function Index, the Manchester Foot Pain and Disability Index, and 12-Item Short Form Health Survey (SF-12) questionnaires, respectively, at the beginning and at days 30, 60, and 90. RESULTS:: A total of 53 patients, aged 59.21 ± 11.38 years, received either the custom-made foot orthoses ( N = 28) or the placebo ( N = 25). For the analysis of the data, only participants who had been measured at the four time points (0, 30, 60, and 90 days) were included. In group A, all variables showed statistically significant differences when comparing the initial and final measurements. Pain showed 6.61 ± 2.33 and 4.11 ± 2.66 in group A, at baseline and at 90 days, respectively, and Group B showed 6.16 ± 1.77 and 5.60 ± 2.71 at baseline and at 90 days, respectively. This was the only variable that showed statistically significant difference between groups ( P = 0.048). CONCLUSION:: The custom-made foot orthoses significantly reduced the participants' foot pain, although they did not have positive effects on disability, foot functionality, and quality of life compared with only cushioning.