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T Gutjahr

Publications and source records attributed to T Gutjahr.

9 recordsLinked to original sources

double-time is identical to discs overgrown, which is required for cell survival, proliferation and growth arrest in Drosophila imaginal discs.

We have isolated the discs overgrown gene of Drosophila and shown that it encodes a homolog of the Casein kinase I(delta)/(epsilon) subfamily and is identical to the double-time gene. However, in contrast to the weak double-time alleles, which appear to affect only the circadian rhythm, discs overgrown alleles, including bona fide null alleles, show strong effects on cell survival and growth control in imaginal discs. Analysis of their phenotypes and molecular lesions suggests that the Discs overgrown protein is a crucial component in the mechanism that links cell survival during proliferation to growth arrest in imaginal discs. This work provides the first analysis in a multicellular organism of Casein kinase I(delta)/(epsilon) functions necessary for survival. Since the amino acid sequences and three-dimensional structures of Casein kinase I(delta)/(epsilon) enzymes are highly conserved, the results suggest that these proteins may also function in controlling cell growth and survival in other organisms.

Amino Acid Sequence↗

Intra-operative epidural morphine, fentanyl, and droperidol for control of pain after spinal surgery. A prospective, randomized, placebo-controlled, and double-blind trial.

The present study was conducted to investigate the analgesic effects of intra-operatively administered epidural morphine in patients undergoing surgery for lumbar disc disease. Three treatment groups were constituted: one with 5.0 mg morphine and 2.5 mg dehydrobenzperidol (DHB) in 10 ml physiological saline, one with 5.0 mg morphine and 0.1 mg fentanyl in the same amount of saline, and one placebo group with saline only. The test solution was injected epidurally via catheter after haemostasis and before closure of the wound. Sixty eight patients were randomly assigned to each of the three groups and subjected to a double-blind evaluation. In the morphine/fentanyl and morphine/droperidol groups, significantly better analgesia was found as compared to the placebo group. No significant difference was found between the morphine/fentanyl and morphine/droperidol groups considering side effects of therapy, as well as duration and quality of analgesia. The side effects in the treatment groups were only slight and not significantly different from the placebo group. It was shown that additional epidural fentanyl offers no significant improvement of postoperative analgesia. No significant reduction of adverse effects could be found in the morphine/droperidol group compared to the morphine/fentanyl group. In conclusion, the intra-operative epidural application of morphine is a safe, effective and simple method for achieving sufficient analgesia in the first 24 hours after lumbar spinal surgery for disc disease.

Analgesia, Epidural↗

The Polycomb-group gene, extra sex combs, encodes a nuclear member of the WD-40 repeat family.

We have delimited the extra sex combs (esc) gene to < 4 kb that include a single transcript and are able to rescue both the maternal and zygotic esc phenotypes. Several mutations have been identified within the esc transcript. In agreement with earlier genetic studies, esc is expressed maternally and its product is most abundant during the early embryonic stages. It encodes a protein of the WD-40 repeat family, which localizes predominantly to the nucleus. During germ band extension, it is expressed in a stereotypic pattern of neuroblasts. We propose a model in which Esc is recruited by gap proteins both to act as a corepressor that competes with the TAFII80 coactivator to block transcription and also to mediate the transition to permanent repression by Polycomb-group proteins.

Amino Acid Sequence↗

Multiple regulatory elements direct the complex expression pattern of the Drosophila segmentation gene paired.

The paired (prd) gene of Drosophila belongs to the pair-rule class of segmentation genes involved in establishing the metameric organization of the Drosophila body plan. The complex expression pattern of prd has previously been shown to depend upon a number of segmentation genes, including gap and pair-rule genes. In an attempt to characterize and analyze the regulatory regions necessary and sufficient for prd expression, we have identified an 18-kb genomic fragment, consisting of the transcribed portion of prd and 10 kb of 5'- and 5 kb of 3'-flanking region, that is able to rescue prd mutant embryos to full viability. Analysis of a series of prd-lacZ fusion constructs containing progressively reduced lengths of prd 5'-flanking sequences delimits different cis-regulatory regions. The entire 5'-flanking region directs fusion gene expression in a pattern similar, but not identical, to the endogenous prd protein pattern. This 10-kb fragment contains both activator and repressor regions that mediate the establishment of the seven-stripe prd pattern, as well as the splitting into anterior and posterior stripes for the 14-stripe expression phase. The prd intron in combination with a minimal upstream region (0.15 kb) is able to direct low levels of prd-lacZ fusion gene expression in stripes. Information for expression of the anterior dorsal spot and of the early seven-stripe pattern is located downstream of the prd coding region. We propose that regulation of prd by pair-rule and gap gene products is mediated by upstream and downstream cis-regulatory elements. Regulation during separate but overlapping phases of expression by separable regulatory regions might be a general characteristic of segmentation genes.

Animals↗

Direct role for Myc in transcription initiation mediated by interactions with TFII-I.

The nuclear proto-oncoprotein Myc has been implicated in the control of cell proliferation and differentiation. Myc participates in transcription and belongs to the basic-helix-loop-helix (bHLH) family of regulatory proteins. Here we show that Myc interacts with TFII-I, a transcription initiation factor that activates core promoters through an initiator element (Inr). As previously observed for the bHLH activator USF, Myc was found to interact cooperatively with TFII-I at both Inr and upstream E-box promoter elements. However, in this case Myc interactions with TFII-I at the Inr lead to an inhibition of transcription initiation. This inhibition is selective for a TFII-I-dependent (as opposed to TFIIA-dependent) initiation pathway and correlates with the prevention of complex formation between the TATA-binding protein TBP (TFIID tau), TFII-I and the promoter. TBP probably interacts with Myc, but only slowly. These observations indicate that Myc has the potential to interact physically and functionally with components of the general transcription machinery.

Adenoviridae↗

Separable regulatory elements mediate the establishment and maintenance of cell states by the Drosophila segment-polarity gene gooseberry.

During Drosophila embryogenesis, position along the anteroposterior axis is specified within each segment by the products of the segment-polarity genes which include wingless (wg) and gooseberry (gsb). The striped expression of these genes in each segment is initially established by the pair-rule gene products during late blastoderm. This pattern is subsequently maintained after germ band extension by interaction among the segment-polarity genes themselves. Here we show that the maintenance of gsb, a PHox gene encoding a paired-domain and a homeodomain, is controlled by the wg signal, the homolog of the murine Wnt-1 protein. A control element responsible for wg-dependent maintenance of gsb expression, gsb-late element, is separable from an element required for the initial activation of gsb by pair-rule transcription factors, gsb-early element. The significance of such a regulatory strategy is discussed with respect to the establishment and maintenance of cell states within each segment by segment-polarity genes.

Animals↗

Complex regulation of early paired expression: initial activation by gap genes and pattern modulation by pair-rule genes.

The paired gene is one of approximately 30 zygotic segmentation genes responsible for establishing the segmented body plan of Drosophila melanogaster. To gain insight into the mechanism by which the paired gene is expressed in a complex temporal and spatial pattern, we have examined paired protein expression in wild-type and mutant embryos. In wild-type embryos, paired protein is expressed in several phases. Initial expression in broad domains evolves into a pair-rule pattern of eight stripes during cellularization. Subsequently, a segment-polarity-like pattern of fourteen stripes emerges. Later, at mid-embryogenesis, paired is expressed in specific regions of the head and in specific cells of the central nervous system. Analysis of the initial paired expression in the primary pair-rule mutants even-skipped, runt and hairy, and in all gap mutants suggests that the products of the gap genes hunchback, Krüppel, knirps and giant activate paired expression in stripes. With the exception of stripe 1, which is activated by even-skipped, and stripe 8, which depends upon runt, the primary pair-rule proteins are required for subsequent modulation rather than activation of the paired stripes. The factors activating paired expression in the pair-rule mode appear to interact with those activating it along the dorsoventral axis.

Animals↗

Analysis of the gooseberry locus in Drosophila embryos: gooseberry determines the cuticular pattern and activates gooseberry neuro.

The segment-polarity class of segmentation genes in Drosophila are primarily involved in the specification of sub-segmental units. In addition, some of the segment-polarity genes have been shown to specify cell fates within the central nervous system. One of these loci, gooseberry, consists of two divergently transcribed genes, gooseberry and gooseberry neuro, which share a paired box as well as a paired-type homebox. Here, the expression patterns of the two gooseberry gene products are described in detail. The gooseberry protein appears in a characteristic segment-polarity pattern of stripes at gastrulation and persists until head involution. It is initially restricted to the ectodermal and neuroectodermal germ layer, but is later detected in mesodermal and neuronal cells as well. The gooseberry neuro protein first appears during germ band extension in cells of the central nervous system and also, much later, in epidermal stripes and in a small number of muscle cells. P-element-mediated transformation with the gooseberry gene has been used to demonstrate that gooseberry transactivates gooseberry neuro and is sufficient to rescue the gooseberry cuticular phenotype in the absence of gooseberry neuro.

Animals↗