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Biomedical subjects

F Sauer

Publications and source records attributed to F Sauer.

At least 37 records · Page 2Linked to original sources

Exact cone beam CT with a spiral scan.

A method is developed which makes it possible to scan and reconstruct an object with cone beam x-rays in a spiral scan path with area detectors much shorter than the length of the object. The method is mathematically exact. If only a region of interest of the object is to be imaged, a top circle scan at the top level of the region of interest and a bottom circle scan at the bottom level of the region of interest are added. The height of the detector is required to cover only the distance between adjacent turns in the spiral projected at the detector. To reconstruct the object, the Radon transform for each plane intersecting the object is computed from the totality of the cone beam data. This is achieved by suitably combining the cone beam data taken at different source positions on the scan path; the angular range of the cone beam data required at each source position can be determined easily with a mask which is the spiral scan path projected on the detector from the current source position. The spiral scan algorithm has been successfully validated with simulated cone beam data.

Algorithms↗

A randomized clinical trial comparing misoprostol with prostaglandin E2 gel for preinduction cervical ripening.

OBJECTIVE: Our purpose was to perform a randomized trial comparing intravaginal misoprostol to intravaginal prostaglandin E2 gel for preinduction cervical ripening evaluating efficacy and side effects. STUDY DESIGN: Seventy-five women seen for induction of labor were randomized to receive 100 micrograms of intravaginal misoprostol or 5 mg of pharmacy-prepared intravaginal prostaglandin E2 gel for cervical ripening before oxytocin induction. Six hours after placement of the study agent, patients were given oxytocin if they were not in labor. The primary outcome measure was induction-to-delivery time; secondary measures were change in Bishop score, delivery mode, and side effects. Results were analyzed by the Student t test and Fisher's exact test, with p < 0.05 considered significant. RESULTS: There was no difference in the incidence of primiparity or the median initial Bishop score between the two study groups. The mean time to delivery and the need for oxytocin was significantly less for subjects receiving misoprostol. There was no difference in the incidence of uterine hyperstimulation syndrome or cesarean delivery between the groups. CONCLUSIONS: This randomized clinical trial indicates that misoprostol is efficacious for preinduction cervical ripening. Misoprostol use resulted in a significantly shorter induction-to-delivery time compared with prostaglandin E2 gel use. The side effects associated with misoprostol may be dose related, and further studies to identify the optimum dosage and interval are needed.

Adult↗

Mechanisms of transcriptional activation: differences and similarities between yeast, Drosophila, and man.

Activation of transcription requires an interplay between enhancer-binding factors and components of the general transcription machinery. New developments within the past few years suggest that novel cofactors are required for relaying specific activation signals to the RNA polymerase II transcription complex in order to achieve enhanced levels of mRNA synthesis. The role of these different cofactors in mediating activation and potential differences in their utilization by divergent organisms, however, raise new questions about the mechanisms of transcriptional regulation.

Animals↗

TAF(II)s mediate activation of transcription in the Drosophila embryo.

Mutations in the genes for two highly conserved TAFs, TAF(II)60 and TAF(II)110, reduce transcription of Bicoid-dependent target genes in vivo. By means of several distinct genetic test systems, specific activator-TAF interactions are shown to support both simple and synergistic enhancement of transcription in the embryo. These studies provide in vivo evidence that TAFs can serve as coactivators to receive gene-specific transcriptional activation signals. This genetic system also presents the opportunity to study the function of basal transcription components in regulating development of complex organisms.

Alleles↗

Gene regulation in the Drosophila embryo.

Pattern formation in Drosophila depends on hierarchical interactions between the maternal and zygotic gene activities which subdivide the embryo into increasingly smaller metameric units along the anterior posterior axis. Here we describe those genes that encode the transcription factors which control precisely the expression of subordinate transcription factors in time and space. This regulation operates through the protein-protein interactions between transcription factors bound to the cis-acting enhancers, which eventually determine the frequency of transcription initiation by polymerase II. Our data show that taking into account the multiple transcriptional activators and repressors that bind to a typical enhancer element, it is likely that the regulation of gene expression in a given cell is defined by their concentration-dependent interplay which directs target gene expression in a position-dependent fashion.

Animals↗

Multiple TAFIIs directing synergistic activation of transcription.

Coordinate activation of transcription by multiple enhancer binding factors is essential for the regulation of pattern formation during development of Drosophila melanogaster. Cell-free transcription reactions are described that recapitulate transcriptional synergism directed by the Drosophila developmental regulators Bicoid (BCD) and Hunchback (HB). Within the basal transcription factor complex TFIID, two specific targets, TAFII110 and TAFII60, served as coactivators to mediate transcriptional activation by these two enhancer binding proteins. A quadruple complex containing TATA binding protein (TBP), TAFII250, TAFII110, and TAFII60 mediated transcriptional synergism by BCD and HB, whereas triple TBP-TAFII complexes lacking one or the other target coactivator failed to support synergistic activation. Deoxyribonuclease I footprint protection experiments revealed that an integral step leading to transcriptional synergism involves the recruitment of TBP-TAFII complexes to the promoter by way of multivalent contacts between activators and selected TAFIIs. Thus, the concerted action of multiple regulators with different coactivators helps to establish the pattern and level of segmentation gene transcription during Drosophila development.

Animals↗

DNA template and activator-coactivator requirements for transcriptional synergism by Drosophila bicoid.

The template and coactivator requirements for synergistic transcription directed by a single activator, Bicoid (BCD), bound to multiple sites have been determined. Mutagenesis studies in combination with protein binding experiments and reconstituted transcription reactions identified two independent activation domains of BCD that target different coactivator subunits (TAFII110 and TAFII60) of the basal transcription factor IID (TFIID). The presence of both coactivators is required for BCD to recruit the TATA binding protein (TBP)-TAF complex to the promoter and direct synergistic activation of transcription. Thus, contact between multiple activation domains of BCD and different targets within the TFIID complex can mediate transcriptional synergism.

Animals↗

Heterodimeric Drosophila gap gene protein complexes acting as transcriptional repressors.

The Drosophila gap gene Krüppel (Kr) encodes a transcriptional regulator. It acts both as an integral part of the Drosophila segmentation gene in the early blastoderm and in a variety of tissues and organs at later stages of embryogenesis. In transfected tissue culture cells, the Kr protein (Kr) was shown to both activate and repress gene expression in a concentration-dependent manner when acting from a single binding site close to the promoter. Here we show that KR can associate with the transcription factors encoded by the gap genes knirps (kni) and hunchback (hb) which affect KR-dependent gene expression in Drosophila tissue culture cells. The association of DNA-bound hb protein or free kni protein with distinct but different regions of KR results in the formation of DNA-bound transcriptional repressor complexes. Our results suggest that individual transcription factors can associate to form protein complexes which act as direct repressors of transcription. The interactions shown here add an unexpected level of complexity to the control of gene expression.

Animals↗

Control of transcription by Krüppel through interactions with TFIIB and TFIIE beta.

The zinc-finger protein Krüppel (Kr) is an integral part of the Drosophila segmentation gene cascade and is essential in organogenesis during later embryonic development. In tissue culture, Kr regulates transcription. Monomeric Kr can act as a transcriptional activator, whereas Kr dimers formed at high concentrations cause repression. Here we show that Kr-dependent control of transcription involves functional interactions with components of the basal RNA polymerase II transcription machinery, which includes the initiation factors TFIIA, B, E, F, H and I (refs 10, 11) as well as the TATA-binding protein (TBP) and TBP-associated factors (TAFs) contained in the multisubunit TFIID (ref. 12). Our results indicate that when acting from a site close to a basal promoter, monomeric Kr interacts with TFIIB to activate transcription, whereas an interaction of the Kr dimer with TFIIE beta, a subunit of TFIIE, results in transcriptional repression.

Animals↗

Functional and conserved domains of the Drosophila transcription factor encoded by the segmentation gene knirps.

The Drosophila gap gene knirps (kni) is required for abdominal segmentation. It encodes a steroid/thyroid orphan receptor-type transcription factor which is distributed in a broad band of nuclei in the posterior region of the blastoderm. To identify essential domains of the kni protein (KNI), we cloned and sequenced the DNA encompassing the coding region of nine kni mutant alleles of different strength and kni-homologous genes of related insect species. We also examined in vitro-modified versions of KNI in various assay systems both in vitro and in tissue culture. The results show that KNI contains several functional domains which are arranged in a modular fashion. The N-terminal 185-amino-acid region which includes the DNA-binding domain and a functional nuclear location signal fails to provide kni activity to the embryo. However, a truncated KNI protein that contains additional 47 amino acids exerts rather strong kni activity which is functionally defined by a weak kni mutant phenotype of the embryo. The additional 47-amino-acid stretch includes a transcriptional repressor domain which acts in the context of a heterologous DNA-binding domain of the yeast transcriptional activator GAL4. The different domains of KNI as defined by functional studies are conserved during insect evolution.

Amino Acid Sequence↗

Dimerization and the control of transcription by Krüppel.

Krüppel (KR), a Drosophila zinc finger-type transcription factor, can both activate and repress gene expression through interaction with a single DNA-binding site. The opposite regulatory effects of KR are concentration-dependent, and they require distinct portions of KR such as the N-terminal region for activation and the C-terminal region for repression. Here we show that KR is able to form homodimers through sequences located within the C terminus. When these sequences were fused to separated functional parts of the yeast transcription factor GAL4, they reconstituted a functional transcriptional activator on dimerization in vivo. Our results suggest that the KR monomer is a transcriptional activator. At higher concentration KR forms a homodimer and becomes a repressor that functions through the same target sequences as the activator.

Animals↗

Transcriptional cascades in Drosophila.

Genetics and molecular analyses have combined to yield insights into a functional cascade of transcription factors necessary to establish the molecular blueprint of the Drosophila body pattern in response to positional information in the egg. Recent progress in this field raises exciting questions regarding the molecular mechanisms involved, and their conservation in biological pattern-forming processes.

Animals↗