TY - JOUR A1 - Winkler, Christoph A1 - Wittbrodt, Joachim A1 - Lammers, Reiner A1 - Ullrich, Axel A1 - Schartl, Manfred T1 - Ligand-dependent tumor induction in medakafish embryos by a Xmrk receptor tyrosine kinase transgene N2 - Xmrk encodes a subclass 1 receptor tyrosine kinase (RTK) which has been cloned from the melanomainducing locus Tu of the poeciliid fish Xiphophorus. To demonstrate a high oncogenic potential in vivo we transferred the gene into early embryos of the closely related medakafish. Ectopic expression of the Xmrk oncogene under the control of a strong, constitutive promoter (CMVTk) led to the induction of embryonic tumors with high incidence, after short latency periods, and with a specific pattern of affected tissues. We demonstrate ligand-dependent transformation in vivo using a chimeric receptor consisting of the extracellular and transmembrane domains of the human EGF receptor (HER) and the cytoplasmatic domain of Xmrk. Expression of the chimeric receptor alone does not lead to ldnase activation or induction of tumors. Coexpression of the chimera with its corresponding ligand, human transforming growth factor alpha (bTGF(X), however, results in the activation of the chimeric RTK. In injected fish embryos the induction of the neoplastic growth is observed with similar incidence and tissue distribution as in embryos carrying the native Xmrk oncogene suggesting that the ligand as well as factors downstream of tbe RTK are required for tumor formation. In this study we show single-step induction of tumors by ectopic expression of RTKs in vivo substantiating tbe significance of autocrine stimulation in RTK induced tumors in vertebrales. KW - Japankärpfling KW - Ligand KW - Tumor Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87107 ER - TY - JOUR A1 - Vortkamp, Andrea A1 - Gessler, Manfred A1 - Paslier, D. Le A1 - Elaswarapu, R. A1 - Smith, S. A1 - Grzeschik, Karl-Heinz T1 - Isolation of a yeast artificial chromosome contig spanning the Greig cephalopolysyndactyly syndrome (GCPS) gene region N2 - Disruption of the zinc finger gene GLI3 has been shown to be the cause of Greig cephalopolysyndactyly syndrome (GCPS), at least in some GCPS translocation patients. To characterize this genomic region on human chromosome 7p13, we have isolated a VAC contig of more than 1000 kb including the GLI3 gene. In this contig the gene itself spans at least 200-250 kb. A CpG island is located in the vicinity of the 5' region of the known GLI3 cDNA, implying a potential promoter region. Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-30182 ER - TY - JOUR A1 - Tony, H. P. A1 - Shen, B. J. A1 - Reusch, P. A1 - Sebald, Walter T1 - Design of human interleukin-4 antagonists inhibiting interleukin-4-dependent and interleukin-13-dependent responses in T-cells and B-cells with high efficiency N2 - Human interleukin-4 possesses two distinct sites for receptor activation. A signaHing site, comprising residues near the C-terminus on helix D, determines the efficacy of interleukin-4 signal transduction without affecting the binding to the interleukin-4 receptor a subunit. A complete antagonist and a series of low-efficacy agonist variants of human interleukin-4 could be generated by introducing combinations of two or three negatively charged aspartic acid residues in this site at positions 121, 124, and 125. One of the double variants, designated [R121D,Y124D]interleukin-4, with replacements of böth Arg121 and Tyr124 by aspartic acid residues was completely inactive in all analysed cellular responses. The loss of efficacy in [R121D,Y124D]interleukin-4 is estimated to be larger than 2000-fold. Variant [R121D,Y124D]interleukin-4 was also a perfect antagonist for inhibition of interleukin-13-dependent responses in B-cells and the TF-1 cellline with a K\(_i\) value of approximately 100 pM. In addition, inhibition of both interleukin-4-induced and interleuk.in-13- induced responses could be obtained by monoclonal antibody X2/45 raised against interleukin-4Rm the extracellular domain of the interleuk.in-4 receptor a subunit. These results indicate that efficient interleukin-4 antagonists can be designed on the basis of a sequential two-step activation model. In addition, the experiments indicate the functional participation of the interleukin-4 receptor a subunit in the interleukin-13 receptor system. KW - Biochemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62394 ER - TY - JOUR A1 - Schwarz, Klaus A1 - Hameister, Horst A1 - Gessler, Manfred A1 - Grzeschik, Karl-Heinz A1 - Hansen-Hagge, Thomas E. A1 - Bartram, Claus R. T1 - Confirmation of the localization of the human recombination activating gene 1 (RAG1) to chromosome 11p13 N2 - The human recombination activating gene 1 (RAGl) has previously been mapped to chromosomes 14q and 11 p. Here we confirm the chromosome 11 assignment by two independent approaches: autoradiographic and fluorescence in situ hybridization to metaphase spreads and analysis of human-hamster somatic cell hybrid DNA by the polymerase chain reaction (PCR) and Southern blotting. Our results unequivocally localize RAG1 to llp13. KW - Biochemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59136 ER - TY - JOUR A1 - Schwartz, Faina A1 - Neve, Rachel A1 - Eisenman, Robert A1 - Gessler, Manfred A1 - Bruns, Gail T1 - A WAGR region gene between PAX-6 and FSHB expressed in fetal brain N2 - Developmental delay or mental retardation is a frequent component of multi-system anomaly syndromes associated with chromosomal deletions. Isolation of genes involved in the mental dysfunction in these disorders should define loci important in brain formation or function. We have identified a highly conserved locus in the distal part of 11 p 13 that is prominently expressed in fetal brain. Minimal expression is observed in a number of other fetal tissues. The gene maps distal to PAX-6 but proximal to the loci for brain-derived neurotrophic factor (BDNF) and the beta subunit of follicle stimulating hormone (FSHB), within a region previously implicated in the mental retardation component of some WAGR syndrome patients. Within fetal brain, the corresponding transcript is prominent in frontal, motor and primary visual cortex as weil as in the caudate-putamen. The characteristics of this gene, including the striking evolutionary conservation at the locus, suggest that the encoded protein may function in brain development. KW - Biochemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-59125 ER - TY - CHAP A1 - Schreibman, Martin P. A1 - Schartl, Manfred A1 - Kallman, Klaus D. A1 - Magliulo-Cepriano, Lucia T1 - Molecular approaches to study the genetic regulation of the fish reproductive system N2 - No abstract available. KW - Fische Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-86679 ER - TY - JOUR A1 - Schmuck, R. A1 - Geise, W. A1 - Linsenmair, Karl Eduard T1 - Life cycle strategies and physiological adjustments of Reedfrog Tadpoles (Amphibia, Anura, Hyperoliidae) in relation to environmental conditions. N2 - The relationship between different degrees of intraspecific crowding of reedfrog tadpoles and their physiological responses to a deterioration of the natal pond water quality was examined under laboratory conditions. Tadpoles that were reared at a lower density metamorphosed significantly earlier than those raised at a higher density. As density increases, the average body length at metamorphosis decreases. However, at low tadpole density, a significantly higher diversity of body size classes among freshly metamorphosed froglets was observed than under more crowded conditions. Mortality increased during metamorphic climax and was inversely correlated with the tadpole density. In ephemeral ponds, an accumulation of nitrogenous wastes from metabolic processes and/or a concentration by evaporation in prolonged rainless periods can pose a considerable chemical stress to reedfrog tadpoles. Hyperolius viridiflavus ommatostictus responded to an increasing ammonia concentration with an activity increase of the ornithine cycle (intensified urea synthesis). hi contrast, Hyperolius marmoratus taeniatus exhibited a strong tolerance against high ammonia levels. A deterioration of the natal pond water quality caused H. v. ommatostictus and H. v. nitidulus tadpoles to adjust to harsher climatic conditions at the time of metamorphosis. This physiological preadjustment enabled the froglets to start feeding and growing immediately after metamorphosis even at low air humidity and rare precipitation events. In contrast, froglets that were raised in daily refreshed water exhibited high mortality rates if subjected to identical conditions. As one possible indicator of the actual climatic conditions prevailing in the surrounding terrestrial habitat, fluctuations in the water ammonia level are discussed. Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31009 ER - TY - JOUR A1 - Scheer, Ulrich A1 - Weisenberger, Dieter T1 - The nucleolus N2 - No abstract available Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-32037 ER - TY - JOUR A1 - Scheer, Ulrich T1 - Harold Garnet Callan 1917-1993 N2 - Professor Harold Gamet Callan, honorary member of the German Society for Cell Biology, died on the 3rd November 1993, at the age of 76. His name is inseparably connected with lampbrush chromosomes, the most spectacular and aesthetically ailuring form of chromosomes, which occupied the major part of his scientific career. " Mick" Callan's pioneering studies led to fruitful new concepts, served as a building block for many subsequent studies by others, and contributed enormously to our current understanding of chromosome organization and activity ... KW - Harold Garnet Callan Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-80789 ER - TY - JOUR A1 - Schartl, A. A1 - Dimitrijevic, N. A1 - Schartl, Manfred T1 - Evolutionary origin and molecular biology of the melanoma-inducing oncogene of Xiphophorus N2 - No abstract available KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61954 ER - TY - JOUR A1 - Reusch, P. A1 - Arnold, S. A1 - Heusser, C. A1 - Wagner, K. A1 - Weston, B. A1 - Sebald, Walter T1 - Neutralizing monoclonal antibodies define two different functional sites in human interleukin-4 N2 - Human interleukin-4 (IL-4) is a small four-helix-bundle protein which is essential for organizing defense reactions against macroparasites, in particular helminths. Human IL-4 also appears to exert a pathophysiological role during various IgE-mediated allergic diseases. Seven different monoclonal antibodies neutralizing the activity of human IL-4 were studied in order to identify functionally important epitopes. A collection of 41 purified IL-4 variants was used to analyse how defined amino acid replacements affect binding affinity for each individual mAb. Specific amino acid positions could be assigned to four different epitopes. mAbs recognizing epitopes on helix A and/or C interfered with IL-4 receptor binding and thus inhibited IL-4 function. However, other mAbs also inhibiting IL-4 function recognized an epitope on helix D of IL-4 and did not inhibit IL-4 binding to the receptor protein. One mAb, recognizing N-terminal and C-terminal residues, partially competed for binding to the receptor. The results of these mAb epitope analyses confirm and extend previous data on the functional consequences of the amino acid replacements which showed that amino acid residues in helices A and C of IL-4 provide a binding site for the cloned IL-4 receptor and that a signalling site in helix D interacts with a further receptor protein. KW - Biochemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62418 ER - TY - JOUR A1 - Nakayama, Ichiro A1 - Foresti, Fausto A1 - Tewari, Rita A1 - Schartl, Manfred A1 - Chourrout, Daniel T1 - Sex chromosome polymorphism and heterogametic males revealed by two cloned DNA probes in the ZW/ZZ fish Leporinus elongatus N2 - In order to study the divergence of teleost sex chromosomes, subtractive cloning was carried out between genomic DNA ofmales and females ofthe rainbow trout (XX/XY) and of Leporinus elongatus (ZW /ZZ). Inserts cloned in a plasmid vector were individually tested on Southern blots of DNA of males and females for sex specificity. No sex-specific insert was obtained from trout, but two out of ten inserts cloned from L. elongatus showed sex-specific patterns in this species: one corresponds to a sequence present on both Z and W chromosomes, while the other is W specific. Sequences of these two inserts show neither clear homology with other known sequences, nor an open reading frame. They cross-hybridize with the genomic DNA of Leporinusfriderici, but without sex-specific patterns. Twenty-four L. elongatus adults were sexed by gonadal observation, chromosomed examination and Southern hybridization with one or the other insert. Ten males and 11 females had chromosomes and hybridization patterns typical of their sex. One ZW female was recognized as a male with the W-specific probe. This was also the case for two unusual ZW males, one having a male hybridization pattern with the other probe. These three atypical individuals may result from single genetic exchanges between four regions of the Z and the W, giving rise to three atypical W chromosomes. Finding males with such atypical heterochromosomes in a female heterogametic species may indicate that a gradual transition occurs between the heterogametic systems. KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61583 ER - TY - JOUR A1 - Müller, T. A1 - Sebald, Walter A1 - Oschkinat, H. T1 - Antagonist design through forced electrostatic mismatch N2 - No abstract available KW - Biochemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62408 ER - TY - JOUR A1 - Müller, T. A1 - Dieckmann, T. A1 - Sebald, Walter A1 - Oschkinat, H. T1 - Aspects of receptor binding and signalling of interleukin-4 investigated by site-directed mutagenesis and NMR spectroscopy N2 - Cytokines are hormones that carry information from ceJI to ceH. This information is read from their surface upon binding to transmembrane receptors and by the subsequent initiation of receptor oligomerization. An inftuence on this process through mutagenesis on the hormone surface is highly desirab)e for medical reasons. However, an understanding of hormone-receptor interactions requires insight into the structural changes introduced by the mutations. In this line structural studies on human TL-4 and the medically important IL-4 antagonists YI24D and Y124G are presented. The site a.round YI24 is an important epitope responsible for the a.bility of 11-4 t.o ca.use a signal in the target cells. It is shown that the local main-chain structure around residue 124 in the variants remains unchanged. A strategy is presented here which allows the study of these types of proteins and their variants by NMR which does not require carbon Iabeiied sa.mples. KW - Biochemie KW - Interleukin-4 KW - protein structure KW - NMR KW - signal transduction Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-62444 ER - TY - JOUR A1 - Meyer, Axel A1 - Morrissey, Jean M. A1 - Schartl, Manfred T1 - Recurrent origin of a sexually selected trait in Xiphophorus fishes inferred from a molecular phylogeny N2 - DARWIN\(^1\) believed that sexual selection accounts for the evolution of exaggerated male ornaments, such as the sword-like caudal fin extensions of male fishes of the genus Xiphophorus, that appear detrimental to survival. Swordtails continue to feature prominently in empirical work and theories of sexual selection; the pre-existing bias hypothesis has been offered as an explanation for the evolution of swords in these fishes\(^{2,3}\). Based upon a largely morphological phylogeny, this hypothesis suggests that female preference to mate with sworded males arose in ancestrally swordless species, thus pre-dating the origin of the sword itself and directly driving its evolution. Here we present a molecular phylogeny (based on mitochondrial and nuclear DNA sequences) of Xiphophorus which differs from the traditional one: it indicates that the sword originated and was lost repeatedly. Our phylogeny suggests that the ancestor of the genus is more likely to have possessed a sword than not, thus questioning the applicability of the pre-existing bias hypothesis as an explanation for the cvolution of this sexually selected trait. KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61569 ER - TY - JOUR A1 - Maschwitz, Ulrich A1 - Fiala, Brigitte A1 - Linsenmair, Karl Eduard T1 - Clerodendrum fistulosum (Verbenanceae), an unspecific myrmecophyte from Borneo with spontaneously opening domatia N2 - Clerodendrumjistulosum Becc. is a true myrmecophyte as it offers nesting space for ants in hollow intemodes. In contrast to previous reports our investigations proved that these domatia open by themselves, thus providing cavities for a variety of different ant species. In Sarawak, Malaysia, we did not find an obligate relationship between C. jistulosum and a specific ant-partner. For comparison, studies on herbarium material of other Clerodendrum species were carried out a further species, C. deflexum from the Malay Peninsula and Sumatra presumably also is myrmecophytic. Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31013 ER - TY - JOUR A1 - Maschwitz, Ulich A1 - Fiala, Brigitte A1 - Saw, L. G. A1 - Norma-Rashid, Yusoff A1 - Idris, Azarae Haji T1 - Ficus obscura var. borneensis (Moraceae), a new non-specific ant-plant from Malesia N2 - Ficus obscura var. borneensis is a true myrmecophyte. It spontaneously forms cavities (domatia) in parts of its twigs which open by slits, These occur in the internodes and are usually not swollen. The domatia are inhabited by a variety of non-specific tree-living ants including Crematogaster spp., Cataulacus sp., Tetramorium sp., Cardio condyla sp. and Camponotus sp.. Additionally the plant providL a su~ar-containing secretion from extrafloral nectaries on the lower surfaces of the leaves. Examination of herbarium specimens of 37 other South-east Asian Ficus species did not reveal a single specimen with domatia. Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-42926 ER - TY - JOUR A1 - Malitschek, Barbara A1 - Wittbrodt, Joachim A1 - Fischer, Petra A1 - Lammers, Reiner A1 - Ullrich, Axel A1 - Schartl, Manfred T1 - Autocrine stimulation of the Xmrk receptor tyrosine kinase in Xiphophorus melanoma cells and identification of a source for the physiological ligand N2 - The melanoma·inducing gene of Xiphophorus fish encodes the Xmrk receptor tyrosine kinase. U sing a highly specific antiserum p~oduced against the recombinant receptor expressed with a baculovirus, it is shown that Xmrk is the most abundant phosphotyrosine protein in fish melanoma and thus highly activated in the tumors. Studies on a melanoma cellline revealed that these cells produce an activity that considerably stimulates receptor autophosphorylation. The stimulating activity induces receptor down-regulation and can be depleted from the melanoma cellsupernatant by the immobilized recombinant receptor protein. The fish melanoma cells can thus be considered autocrine tumor cells providing a source for future purification and characterization of the Xmrk ligand. KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61551 ER - TY - JOUR A1 - Lubjuhn, T. A1 - Schartl, Manfred A1 - Epplen, J. T. T1 - Methodik und Anwendungsgebiete des genetischen Fingerabdruckverfahrens N2 - No abstract available KW - Physiologische Chemie Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61978 ER - TY - JOUR A1 - Linsenmair, Karl Eduard T1 - Biologische Vielfalt und ökologische Stabilität N2 - No abstract available Y1 - 1994 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31157 ER -