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M Hoch

Publications and source records attributed to M Hoch.

At least 37 records · Page 2Linked to original sources
PubMed1996

Germ line and embryonic expression of Fex, a member of the Drosophila F-element retrotransposon family, is mediated by an internal cis-regulatory control region.

The F elements of Drosophila melanogaster belong to the superfamily of long interspersed nucleotide element retrotransposons. To date, F-element transcription has not been detected in flies. Here we describe the isolation of a member of the F-element family, termed Fex, which is transcribed in specific cells of the female and male germ lines and in various tissues during embryogenesis of D. melanogaster. Sequence analysis revealed that this element contains two complete open reading frames coding for a putative nucleic acid-binding protein and a putative reverse transcriptase. Functional analysis of the 5' region, using germ line transformation of Fex-lacZ reporter gene constructs, demonstrates that major aspects of tissue-specific Fex expression are controlled by internal cis-acting elements that lie in the putative coding region of open reading frame 1. These sequences mediate dynamic gene expression in eight expression domains during embryonic and germ line development. The capacity of the cis-regulatory region of the Fex element to mediate such complex expression patterns is unique among members of the long interspersed nucleotide element superfamily of retrotransposons and is reminiscent of regulatory regions of developmental control genes.

Amino Acid Sequence↗
PubMed1995

Ca2+ entry and vasoconstriction during osmotic swelling of vascular smooth muscle cells.

Exposure of aortic strips from guinea-pigs to hypotonic extracellular fluid is followed by marked vasoconstriction, which is inhibited by D-600 (3 microM), a blocker of voltage-sensitive Ca2+ channels. Conventional electrophysiology, patch-clamp studies, pH determination with 2',7' bis(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF) and Ca2+ measurements with Fura-2 have been performed on smooth muscle cells cultured either from rat or human aorta to further elucidate the underlying mechanisms. Exposure of the cells to a 25% hypotonic extracellular fluid leads to a rapid and fully reversible depolarization, paralleled by an increase of the selectivity and conductance of the cell membrane to Cl-, an acidification of the cytoplasm and an increase of intracellular Ca2+ concentration ([Ca2+]i). The latter is inhibited by the Ca2+ channel blocker D-600 (1-3 microM). It is concluded that osmotic cell swelling leads to the activation of an anion channel. The subsequent depolarization of the cell membrane activates voltage-sensitive Ca2+ channels which increases [Ca2+]i, thus stimulating the contraction of vascular smooth muscle cells.

Animals↗
PubMed1995

Control of epithelial morphogenesis by cell signaling and integrin molecules in the Drosophila foregut.

Coordinated cell movements are critical for tissue and organ morphogenesis in animal development. We show that the Drosophila genes hedgehog and wingless, which encode signaling molecules, and the gene myospheroid, which encodes a beta subunit of the integrins, are required for epithelial morphogenesis during proventriculus development. In contrast, this morphogenetic process is suppressed by the decapentaplegic gene, which encodes a member of the TGF beta family of growth factors. These results identify a novel cell signaling center in the foregut that directs the formation of a multiply folded organ from a simple epithelial tube.

Animals↗
PubMed1995

[Combination of mitoxantrone-vinorelbine as first-line chemotherapy for metastatic breast carcinoma].

A phase II trial was performed to assess the efficacy and toxicity of the combination mitoxantrone (MXN) and vinorelbine (VNR) as first-line chemotherapy for metastatic breast cancer. Forty-one patients with metastatic disease or local relapse recruited between March 1991 and April 1993 received a first-line chemotherapy treatment consisting in 12 mg/m2 intravenous (IV) bolus of MXN on day 1 followed by a 20-minute perfusion of 25 mg/m2 of VNR on days 1 and 8. Cycles were repeated every 21 days until evidence of disease progression or of severe toxicity. Thirty-seven patients were evaluable for response and all 41 for toxicity. An objective response was observed in 19 patients (51%; 95% confidence interval, 45 to 74%). The response was complete in a further 11 (30%). Median time to treatment failure was 9 months. Median survival was 14 months. There were no treatment-related deaths. Limiting toxicity was myelosuppression. Leukopenia occurred in 29 patients (71%) and was grade 3 or 4 in nine of these (15%). Grade 2 or 3 anemia was encountered in six patients (15%), grade 1 thrombocytopenia in one, neurotoxicity (constipation) in two, and grade 2 or 3 alopecia in 12 (29%). Nausea/vomiting requiring antiemetic treatment was experienced by only two patients (5%). There were two cases of septicemia treated by antibiotic therapy in hospital.

Adult↗
PubMed1994

The interaction of DNA with the DNA-binding domain encoded by the Drosophila gene fork head.

The Drosophila gene fork head (fkh) encodes a nuclear protein which shares sequence similarity with the rat hepatocyte-enriched transcription factor family HNF3 alpha-gamma. The sequence similarity is restricted to the region that has been defined as the DNA-binding domain of these proteins, termed the fork head domain. In this study, we investigate the structural properties of the fork head domain of the prototype of this protein family encoded by fkh and its interaction with DNA. The core sequence required for DNA binding of the fork head domain consists of 114 amino acids and represents a stable and highly compact monomer of globular structure with an alpha-helix content of 37%. The fork head domain binds specifically to the DNA target sequence of HNF3 alpha-gamma and to an enhancer element that is derived from a regulatory sequence of an in vivo Drosophila target gene. The specific interaction between the DNA-binding domain of the fkh-encoded protein and its target DNA is mediated by two contact regions which are separated from each other by one turn of the DNA. Our data are consistent with a structural model which derived rom X-ray diffraction analysis of the DNA-binding domain of HNF3 gamma. Differences concerning the DNA contact sites between the DNA-binding domain of the fkh-encoded protein and the HNF3 protein family are discussed.

Animals↗
PubMed1994

Sequential fates in a single cell are established by the neurogenic cascade in the Malpighian tubules of Drosophila.

In each Malpighian tubule of Drosophila, one cell is singled out, the tip cell, whose function during embryogenesis is to promote cell division in its neighbours. We follow the segregation of this cell, explore the genetic interactions that underlie its specification and demonstrate that tip cell allocation closely resembles neurogenesis. The tip cell arises by division of a tip mother cell, which is selected from a cluster of equivalent cells in each tubule primordium. Each cluster is marked out by the expression of proneural genes and the selection of a single cell from each group involves lateral inhibition, mediated by the neurogenic genes. We confirm the mitogenic role of the tip cell during embryogenesis by mutational analysis and show that it subsequently adopts a second fate, differentiating neural characteristics. We demonstrate that both stages in the differentiation of this cell are established by the same sequence of genetic interactions, which have not previously been shown to occur outside the neurogenic ectoderm.

Animals↗
PubMed1993

Transcriptional regulation and spatial patterning in Drosophila.

Pattern formation in Drosophila is initiated by a small set of asymmetrically distributed maternal transcription factors that act as graded morphogens along the anterior-posterior and the dorsal-ventral axes of the embryo. Recent progress in the field provides first insight into the molecular mechanisms by which long-range positional information in the egg causes a series of localized zygotic transcription factors to position the developmental fate along the blastoderm.

Animals↗
PubMed1992

Competition for overlapping sites in the regulatory region of the Drosophila gene Krüppel.

A 730-base pair element regulates expression of the Drosophila gap gene Krüppel (Kr) in response to the fly anterior morphogen bicoid (bcd). Two hormone receptor-like proteins, encoded by the genes knirps (kni) and tailless (tll), bind specifically to the element. In vitro, kni protein competes with the homeodomain-containing bcd protein in binding to a 16-base pair target sequence. In vivo experiments suggest that both kni and tll act as competitive repressors of bcd-mediated activation of Kr. These results suggest a mechanism by which developmental genes can be regulated in response to an activating morphogen gradient antagonized by repressors.

Animals↗
PubMed1992

Spatial control of the gap gene knirps in the Drosophila embryo by posterior morphogen system.

The gap genes of Drosophila are the first zygotic genes to respond to the maternal positional signals and establish the body pattern along the anterior-posterior axis. The gap gene knirps, required for patterning in the posterior region of the embryo, can be activated throughout the wild-type embryo and is normally repressed from the anterior and posterior sides. These results provide direct molecular evidence that the posterior morphogen system interacts in a fundamentally different manner than do hunchback and bicoid, which are responsible for anterior pattern formation.

Animals↗
PubMed1992

Transcriptional control by Drosophila gap genes.

The segmented body pattern along the longitudinal axis of the Drosophila embryo is established by a cascade of specific transcription factor activities. This cascade is initiated by maternal gene products that are localized at the polar regions of the egg. The initial long-range positional information of the maternal factors, which are transcription factors (or are factors which activate or localize transcription factors), is transferred through the activity of the zygotic segmentation genes. The gap genes act at the top of this regulatory hierarchy. Expression of the gap genes occurs in discrete domains along the longitudinal axis of the preblastoderm and defines specific, overlapping sets of segment primordia. Their protein products, which are DNA-binding transcription factors mostly of the zinc finger type, form broad and overlapping concentration gradients which are controlled by maternal factors and by mutual interactions between the gap genes themselves. Once established, these overlapping gap protein gradients provide spatial cues which generate the repeated pattern of the subordinate pair-rule gene expression, thereby blue-printing the pattern of segmental units in the blastoderm embryo. Our results show different strategies by which maternal gene products, in combination with various gap gene proteins, provide position-dependent sets of transcriptional activator/repressor systems which regulate the spatial pattern of specific gap gene expression. Region-specific combinations of different transcription factors that derive from localized gap gene expression eventually generate the periodic pattern of pair-rule gene expression by the direct interaction with individual cis-acting "stripe elements" of particular pair-rule gene promoters. Thus, the developmental fate of blastoderm cells is programmed according to their position within the anterior-posterior axis of the embryo: maternal transcription factors regulate the region-specific expression of first zygotic transcription factors which, by their specific and unique combinations, control subordinate zygotic transcription factors, thereby subdividing the embryo into increasingly smaller units later seen in the larva.

Animals↗
PubMed1991

Gene expression mediated by cis-acting sequences of the Krüppel gene in response to the Drosophila morphogens bicoid and hunchback.

The initial expression of the gap gene Krüppel (Kr) occurs in a precisely bounded central region of the Drosophila blastoderm embryo. According to genetic analysis, the spatial limits of the Kr expression domain are controlled by the morphogenetic activities of the anterior organizer gene bicoid (bcd) and the anterior gap gene hunchback (hb). Using gene fusion analysis, we assayed for cis-acting sequences of the Kr gene which mediate transcriptional activation and localized gene expression in response to trans-acting factors. A 730 bp Kr control element drives gene expression in place of the endogenous Kr central domain. This cis-acting element, Kr730, is composed of bcd and hb responsive sequences. They map into regions of multiple hb and bcd protein in vitro binding sites. A 142 bp core fragment containing one low affinity hb and five medium to strong bcd protein binding sites drives gene expression in a Kr-like location in the centre of the embryo. Our results show that this fragment represents a target for the redundant activator/repressor system provided by the anterior morphogens bcd and hb.

Animals↗
PubMed1991

Target sequences for hunchback in a control region conferring Ultrabithorax expression boundaries.

Boundaries of Ultrabithorax expression are mediated by long-range repression acting through the PBX or ABX control region. We show here that either of these control regions confers an early band of beta-galactosidase expression which is restricted along the anteroposterior axis of the blastoderm embryo. This band is succeeded by a stripe pattern with very similar anteroposterior limits. Dissection of the PBX control region demonstrates that the two patterns are conferred by distinct cis-regulatory sequences contained within separate PBX subfragments. We find several binding sites for hunchback protein within both PBX subfragments. Zygotic hunchback function is required to prevent ectopic PBX expression. Moreover, the PBX pattern is completely suppressed in embryos containing uniformly distributed maternal hunchback protein. Our results strongly suggest that hunchback protein directly binds to the PBX control region and acts as a repressor to specify the boundary positions of the PBX pattern.

Animals↗
PubMed1990

cis-acting control elements for Krüppel expression in the Drosophila embryo.

Krüppel (Kr), a gap gene of Drosophila, shows complex spatial patterns of expression during the different stages of embryogenesis. In order to identify cis-acting sequences required for normal Kr gene expression, we analysed the expression patterns of fusion gene constructs in transgenic embryos. In these constructs, bacterial lacZ expression was placed under the control of Kr sequences in front of a basal promoter. We identified cis-acting Kr control units which drive beta-galactosidase expression in 10 known locations of Kr expression in early and late embryos. More than one cis-regulatory element drives the expression in the anterior domain at the blastoderm stage, in the nervous system, the midline precursor cells and in the amino-serosa. In addition, two cis-acting elements direct the first zygotic expression of Kr in a striped subpattern within the central region of the blastoderm embryo. Both elements respond to alterations in the activities of maternal organizer genes known to be required for Kr expression in establishing the thoracic and anterior abdominal segments in the wild-type embryo.

Animals↗
PubMed1989

Krüppel requirement for knirps enhancement reflects overlapping gap gene activities in the Drosophila embryo.

Segmental pattern formation in Drosophila proceeds in a hierarchical manner whereby the embryo is stepwise divided into progressively finer regions until it reaches its final metameric form. Maternal genes initiate this process by imparting on the egg a distinct antero-posterior polarity and by directing from the two polar centres the activities of the zygotic genes. The anterior system is strictly dependent on the product of the maternal gene bicoid (bcd), without which all pattern elements in the anterior region of the embryo fail to develop. The posterior system seems to lack such a morphogen. Rather, the known posterior maternal determinants simply define the boundaries within which abdominal segmentation can occur, and the process that actively generates the abdominal body pattern may be entirely due to the interactions between the zygotic genes. The most likely candidates among the zygotic genes that could fulfil the role of initiating the posterior pattern-forming process are the gap genes, as they are the first segmentation genes to be expressed in the embryo. Here we describe the interactions between the gap genes Krüppel (Kr), knirps (kni) and tailless (tll). We show that kni expression is repressed by tll activity, whereas it is directly enhanced by Kr activity. Thus, Kr activity is present throughout the domain of kni expression and forms a long-range protein gradient, which in combination with kni activity is required for abdominal segmentation of the embryo.

Animals↗
PubMed1989

Synthesis of different nucleoside 5'-diphospho-sulfoquinovoses and their use for studies on sulfolipid biosynthesis in chloroplasts.

6-Sulfo-alpha-D-quinovopyranosyl phosphate was reacted with different nucleoside monophosphate morpholidates to form ADP-, CDP-, GDP- and UDP-sulfoquinovose. Analytical and preparative HPLC of these nucleotides was performed on reversed-phase columns using volatile buffer systems as eluant. The isolated compounds were characterized by NMR spectroscopy (except the CDP derivative) and used for an investigation of sulfolipid biosynthesis by chloroplasts. For this purpose intact spinach chloroplasts were biosynthetically preloaded with radioactive diacylglycerol to provide a sulfoquinovosyl acceptor. When sulfosugar nucleotides were added to such prelabelled intact organelles, the background levels of sulfolipid biosynthesis did not rise. On the other hand, after osmotic shock of prelabelled chloroplasts sulfolipid labelling was significantly increased by the addition of UDP- or GDP-sulfoquinovose. The same stimulation was observed with isolated envelope membranes, and UDP-sulfoquinovose proved to be twice as active as the GDP derivative. From these results it was concluded that the final step in sulfolipid biosynthesis is catalyzed by a UDP-sulfoquinovose: 1,2-diacylglycerol 3-O-alpha-D-sulfoquinovosyltransferase. This chloroplast enzyme cannot use exogenously supplied sulfosugar nucleotides, which as membrane-impermeable compounds are expected to be formed in vivo within chloroplasts.

Bacterial Proteins↗
PubMed1988

[Breast cancer: the role of scintigraphy in the initial evaluation and follow-up of patients with small tumors (T less than or equal to 3 cm)].

To evaluate the utility of bone scans for the follow-up of patients with small breast cancers (T less than or equal to 3 cm), the files for 133 patients whose disease was diagnosed between Jan. 1, 1979 and Dec. 31, 1980 were reviewed. At initial presentation, two of these patients already had bone metastases. During their disease course, 30 patients developed metastases and 16 of them had at least one bone metastasis. In 7 of these 16 cases, the bone metastasis was solitary; in 4 cases bone lesions were symptomatic. A total of 178 bone scans were performed during the follow-up of these 133 patients; 16 of these scans were positive, but only 4 examinations allowed the diagnosis of bone metastasis. Despite the slight prognostic value of initial bone scanning in this series, the technique is of little value unless it is combined with clinical examinations aimed at early detection of disease recurrence or metastasis. Except as part of clinical trial protocols, systematic bone scans appear unnecessary for the staging and follow-up of patients with small breast cancers.

Adult↗