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  • 1
    ISSN: 1432-041X
    Keywords: Key words Pigment pattern ; Fin ; Fish skeleton ; Tyrosinase ; Zebrafish
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract  Mutations causing a visible phenotype in the adult serve as valuable visible genetic markers in multicellular genetic model organisms such as Drosophila melanogaster, Caenorhabditis elegans and Arabidopsis thaliana. In a large scale screen for mutations affecting early development of the zebrafish, we identified a number of mutations that are homozygous viable or semiviable. Here we describe viable mutations which produce visible phenotypes in the adult fish. These predominantly affect the fins and pigmentation, but also the eyes and body length of the adult. A number of dominant mutations caused visible phenotypes in the adult fish. Mutations in three genes, long fin, another long fin and wanda affected fin formation in the adult. Four mutations were found to cause a dominant reduction of the overall body length in the adult. The adult pigment pattern was found to be changed by dominant mutations in wanda, asterix, obelix, leopard, salz and pfeffer. Among the recessive mutations producing visible phenotypes in the homozygous adult, a group of mutations that failed to produce melanin was assayed for tyrosinase activity. Mutations in sandy produced embryos that failed to express tyrosinase activity. These are potentially useful for using tyrosinase as a marker for the generation of transgenic lines of zebrafish.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature structural biology 2 (1995), S. 835-837 
    ISSN: 1072-8368
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Sir—Structural similarity between unrelated proteins has important theoretical and practical consequences. Proteins are often compared by the topology of their secondary structures12. This is difficult, however, for small proteins poor in regular secondary structures, which rely on disulphide ...
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7276
    Keywords: B16 melanoma ; c-met ; HGF/SF ; liver metastasis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Metastasis to the liver is a frequent event in clinical oncology, the molecular mechanisms of which are not fully understood. We have recently reported a consistent overexpression of c-met in B16 melanoma cells selected in vivo for enhanced liver metastatic ability. In this study we address the question as to whether constitutive activation of c-met is a necessary and sufficient condition for enhanced liver colonization B16 melanoma cells. Different levels of c-met expression and/or activation in B16 cells were achieved subcloning, or by c-DNA transfection with either HGF/SF or the oncogenic form of c-met (tpr-met). Metastatic ability of the different populations was then evaluated in vivo by the lung colonization (experimental metastasis) assay. Results indicate that c-met (but not tpr-met) activation in B16 melanoma cells may increase their liver colonizing potential, probably by enhancing motility and invasion in response paracrine interactions with its ligand. C-met expres sion per se, however, is not able to change the organ specificity of the cells. C-met activation appears instead to be required at later stages of liver colonization by B16 melanoma cells, in order to enhance their site-specific metastatic ability. © Rapid Science 1998
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature America Inc.
    Nature genetics 23 (1999), S. 15-16 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] The ability of the immune system to respond to an endless number of foreign antigens is conferred by V(D)J recombination, which occurs specifically in immature lymphocytes and is controlled by the highly conserved recombination activating genes rag1 and rag2 (refs 2–4). Despite the ...
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature America Inc.
    Nature genetics 20 (1998), S. 239-243 
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Defects in the enzymes involved in the haem biosynthetic pathway can lead to a group of human diseases known as the porphyrias. yquem (yqe tp61) is a zebrafish mutant with a photosensitive porphyria syndrome. Here we show that the porphyric phenotype is due to an inherited homozygous mutation ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    Proteins: Structure, Function, and Genetics 31 (1998), S. 445-452 
    ISSN: 0887-3585
    Keywords: chorismate mutase ; activity ; allosteric ; electrostatics ; Chemistry ; Biochemistry and Biotechnology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The predicted active site of chorismate mutase of baker's yeast Saccharomyces cerevisiae has been studied by continuum electrostatics, molecular surface/volume calculations, and molecular modeling. Our study shows that despite being subject to an allosteric transition, the enzyme's active-site pocket neither decreased in volume nor deformed significantly in shape between the active R state and the inactive T state. We find that the polar atmosphere in the pocket is responsible for the enzyme's affinity. A single amino acid, Glu23, can adequately account for the atmospheric variation. This residue swings into the active-site pocket from the R state to the T state. In the R state, Glu23 on helix H2 doubly pairs with Arg204 and Lys208 of H11, which is packed against H2. In the T state, a slide occurs between H11 and H2 such that Glu23 can no longer interact with Lys208 and competes with Asp24 for interacting with Arg204. Consequently, Glu23 is found in the T state to couple with Arg157, an active-site residue critical to substrate binding. The tandem sliding of H11 in both monomers profoundly changes the interactions in the dimer interface. The loop between H11 and H12 demonstrates the largest conformational change. Hence, we establish a connection between the allosteric transition and the activity of the enzyme. The conformational change in the transition is suggested to propagate into the active-site pocket via a series of polar interactions that result in polarity reversal in the active-site pocket, which regulates the enzyme's activity. Proteins 31:445-452, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 71 (1998), S. 264-276 
    ISSN: 0730-2312
    Keywords: HGF/SF ; MSH ; c-met ; tyrosinase ; B16 melanoma ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Reiterated selection in vivo of B16 murine melanoma cells for enhanced liver metastatic ability yielded a cell line (B16-LS9) dramatically overexpressing a constitutively active hepatocyte growth factor/scatter factor (HGF/SF) receptor, the product of the c-met proto-oncogene. Most likely because of their overexpressing c-met, B16-LS9 cells appear to be more responsive than parental B16-F1 cells to HGF stimulation, in terms of motility, invasion, and growth. They are also more pigmented, and express higher levels of tyrosinase as compared to parental B16-F1 cells. Therefore, we set out to explore whether HGF/SF and the liver might influence the differentiation state of B16 cells. We found that HGF/SF and MSH, two factors which reportedly have a strong influence on the phenotype and the malignant behavior of melanoma cells, may act at different levels, and with opposite results, on the regulation of gene expression. In fact, while MSH induces, at the transcriptional level, an increase in the production of both c-met and tyrosinase, HGF/SF, in contrast, promotes a decrease in the expression of both c-met and tyrosinase, however at a posttranscriptional level. These two opposite effects can counter-balance each other, when the cells are treated with both factors at the same time, apparently through a mechanism involving MAP kinase activation. The effects were, however, additive when morphological changes were considered. Most intriguingly, we also describe a very strong downregulatory activity, limited to tyrosinase expression, by hepatocytes in coculture with B16 cells. This activity, also at the posttranscriptional level, is much stronger than that exerted by HGF/SF, and appears to be due to a labile soluble factor produced by the hepatocytes. J. Cell. Biochem. 71:264-276, 1998. © 1998 Wiley-Liss, Inc.
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
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