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  • gene expression  (195)
  • Chemistry
  • Springer  (199)
  • Cell Press
  • 1990-1994  (199)
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  • 1
    ISSN: 1420-9071
    Keywords: Aldehyde dehydrogenase ; developmental changes ; gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Previous reports suggested that the major cytosolic aldehyde dehydrogenase (ALDH1) was present in fetal and infant livers, but the major mitochondrial isozyme (ALDH2) was absent or severely diminished. Re-examination by means of starch gel electrophoresis followed by enzyme activity staining, and by means of dot blot immuno-hybridization of liver samples with known genotypes of theALDH 2 locus, indicated that bothALDH 1 andALDH 2 genes are expressed in fetal and infant livers. In addition, ALDH4 isozyme was also observed. The results imply that a fetus with the ‘usual’ homozygousALDH 2 1 /ALDH 2 1 genotype, but not one with the atypicalALDH 2 1 /ALDH 2 2 orALDH 2 2 /ALDH 2 2 , is capable of detoxifying acetaldehyde transferred from the mother.
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 47 (1991), S. 321-331 
    ISSN: 1420-9071
    Keywords: Symbiosis ; ectomycorrhiza ; ectomycorrhiza development ; gene expression ; ectomycorrhizins ; protein patterns
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary An ectomycorrhiza, a specialized root organ, is the result of a complex interaction leading to a finely-tuned symbiosis between a plant and a compatible ectomycorrhizal fungus. Ultrastructural observations combined with cytochemical and biochemical studies reveal that structural and metabolic changes in the symbiont cells lead to the final phenotype of the active ectomycorrhiza. In the present review these changes are interpreted as changes in gene expression and discussed within the context of ectomycorrhiza development. Recent genetic data indicate that the continued vegetative growth of the ectomycorrhizal hyphae and the root tissues, and their ability to switch to symbiotic organ formation, is basically controlled by developmentally critical genes. The activity of these ‘symbiotic genes’ during the differentiation of ectomycorrhizas is associated with extensive changes in the concentration of particular polypeptides and protein biosynthesis. The present state of knowledge about the developmental biology of ectomycorrhizas allows only speculation about the events during their development.
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 49 (1993), S. 133-137 
    ISSN: 1420-9071
    Keywords: Fetal hemoglobin ; sickle cell anemia ; β thalassemia ; butyrate ; gene expression
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The inherited β-hemoglobinopathies (sickle cell disease and β thalassemia) are the result of a mutation in the adult (β) globin gene. The fetal globin chain, encoded by the γ globin genes, can substitute for the mutated or defective β globin chain, but expression of the γ globin gene is developmentally inactivated prior to birth. Reinducing expression of the normal fetal globin genes is a preferred method of ameliorating sickle cell disease and the β thalassemias. Stimulation of as little as 4–8% fetal globin synthesis in the bone marrow can produce 〉20% fetal hemoglobin in the peripheral circulation, due to enhanced survival of red blood cells containing both sickle and fetal hemoglobin, compared to those containing sickle hemoglobin alone. Butyric acid and butyrate derivatives are generally safe compounds which induce fetal hemoglobin production by stimulating the promoter of the fetal globin genes. An initial trial with the parent compound, delivered as Arginine Butyrate, has demonstrated rapid stimulation of fetal globin expression to levels that have been shown to ameliorate these conditions. Phase 1 trials of an oral butyrate derivative with a long plasma half-life have just begun. These agents now provide a specific new apporach for ameliorating these classic molecular disorders and merit further investigation in larger patient populations.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 50 (1994), S. 958-962 
    ISSN: 1420-9071
    Keywords: Plasminogen activator ; active oxygen ; gene expression ; radical scavengers ; endothelial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Active oxygen, produced by cultured cells following stimulation with various growth factors, seems to be involved in signal transduction leading to cellular responses such as gene expression and growth modulation. In the present study, the intracellular oxidation state was measured in immortalized human endothelial cells (ECV304) after treatment with tumor necrosis factor (TNF)α, using a fluorescent dye and a laser-scanning confocal microscope. The intracellular oxidation state was increased 60 min after the addition of TNFα, and this increase was abolished by a radical scavenger, N-acetylcysteine (NAC), which is also a precursor of glutathione, and by pyrrolidine dithiocarbamate (PDTC). TNFα increased the steady state level of urokinase-type plasminogen activator (uPA), and NAC inhibited this increase at a dose that also inhibited the increase in the intracellular oxidation state. PDTC, on the other hand, did not affect the induction of the uPA gene by TNFα. These results suggest that intracellular glutathione level rather than the oxidation state is necessary for the induction of the uPA gene by TNFα.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 49 (1993), S. 447-455 
    ISSN: 1420-9071
    Keywords: Proteoglycan ; chondroitin sulfate ; decorin ; gene expression ; tumor stroma ; DNA methylation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Tumor stroma is a specialized form of tissue that is associated with epithelial neoplasms. Recent evidence indicates that significant changes in proteoglycan content occur in the tumor stroma and that these alterations could support tumor progression and invasion as well as tumor growth. Our main hypothesis is that the generation of tumor stroma is under direct control of the neoplastic cells and that, via a feedback loop, altered proteoglycan gene expression would influence the behavior of tumor cells. In this review, we will focus primarily on the work from our laboratory related to the altered expression of chondroitin sulfate proteoglycan and its role in tumor development and progression. The connective tissue stroma of human colon cancer is enriched in chondroitin sulfate and the stromal cell elements, primarily colon fibroblasts and smooth muscle cells, are responsible for this biosynthetic increase. These changes can be reproduced in vitro by using either tumor metabolites or co-cultures of human colon carcinoma cells and colon mesenchymal cells. The levels of decorin, a leucine-rich proteoglycan involved in the regulation of matrix assembly and cell proliferation, are markedly elevated in the stroma of colon carcinoma. These changes correlate with a marked increase in decorin mRNA levels and a concurrent hypomethylation of decorin gene, a DNA alteration associated with enhanced gene expression. Elucidation of decorin gene structure has revealed an unexpected degree of complexity in the 5′ untranslated region of the gene with two leader exons that are alternatively spliced to the second coding exon. Furthermore, a transforming growth factor beta (TGF-β)-negative element is present in the promoter region of decorin gene. This regulatory domain is likely to be implicated in the silencing of decorin gene by TGF-β and may contribute to the regulation of this matrix gene in the tumor stroma.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Antonie van Leeuwenhoek 59 (1991), S. 65-76 
    ISSN: 1572-9699
    Keywords: anaerobic respiration ; FNR protein ; oxygen regulation ; gene expression ; E. coli
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Molecular oxygen is an important regulatory signal in facultative anaerobic bacteria and controles the expression of a great variety of genes positively or negatively. The expression of anaerobic respiration and of related functions of E. coli is controlled by the positive gene regulator FNR, which activates transcription in the absence of O2. The regulated genes carry a FNR consensus sequence upstream of the promoter. Under the same conditions FNR represses some of the genes of aerobic respiration. The binding to the DNA occurs by an α-helix-turn-α-helix DNA-binding domain. FNR contains 5 cysteine residues, four of which are arranged in a cluster close to the N-terminal end. For the function of FNR as a O2-dependent regulator three of the cysteine residues in the cluster and the residue outside the cluster are essential. FNR binds iron as a cofactor which most likely is involved in the O2-sensing by the protein. The experiments indicate that the cysteine residues are responsible for the binding of the iron. From the protein in vivo two functional states can be differentiated, an aerobic or metal-depleted form and an anaerobic form. Only the anaerobic form acts as a gene activator or repressor. Sensing of O2 or of positive redox potentials by the iron ion is thought to cause the conversion of the two functional states. The FNR protein in addition contains a potential nucleotide binding domain. The significance and function of this site is not clear.
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Antonie van Leeuwenhoek 62 (1992), S. 131-153 
    ISSN: 1572-9699
    Keywords: mitochondrial DNA ; mutational analysis ; nucleo-mitochondrial interactions ; gene expression ; membrane assembly ; respiratory deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In contrast to most other organisms, the yeastSaccharomyces cerevisiae can survive without functional mitochondria. This ability has been exploited in genetic approaches to the study of mitochondrial biogenesis. In the last two decades, mitochondrial genetics have made major contributions to the identification of genes on the mitochondrial genome, the mapping of these genes and the establishment of structure-function relationships in the products they encode. In parallel, more than 200 complementation groups, corresponding to as many nuclear genes necessary for mitochondrial function or biogenesis have been described. Many of the latter are required for post-transcriptional events in mitochondrial gene expression, including the processing of mitochondrial pre-RNAs, the translation of mitochondrial mRNAs, or the assembly of mitochondrial translation products into the membrane. The aim of this review is to describe the genetic approaches used to unravel the intricacies of mitochondrial biogenesis and to summarize recent insights gained from their application.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 47 (1991), S. 22-31 
    ISSN: 1420-9071
    Keywords: Atherosclerosis ; cellular differentiation ; gene expression ; foam cells ; lipoproteins ; phorbol esters ; transcription factors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary THP-1 is a human monocytic leukemia cell line. After treatment with phorbol esters, THP-1 cells differentiate into macrophage-like cells which mimic native monocyte-derived macrophages in several respects. Compared to other human myeloid cell lines, such as HL-60, U937, KG-1, or HEL cell lines, differentiated THP-1 cells behave more like native monocyte-derived macrophages. Because of these characteristics, the THP-1 cell line provides a valuable model for studying the mechanisms involved in macrophage differentiation, and for exploring the regulation of macrophage-specific genes as they relate to physiological functions displayed by these cells.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 47 (1991), S. 905-912 
    ISSN: 1420-9071
    Keywords: Gene transfer ; gene modification ; gene expression ; livestock ; transgenic animal ; pharmaceutical proteins ; milk composition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract There is every reason to expect that it will be possible within the next few years to begin to use farm animals to produce large quantities of some of the human proteins that are needed for the treatment of disease. Revolutionary new opportunities for the production of novel proteins in milk have been created by the development of methods for gene transfer. Exploitation of these opportunities depends upon selection and cloning of milk protein genes and identification of the sequences that govern tissue specific hormonally induced expression in the mammary gland. Studies with three genes, ovine β-lactoglobulin, rat β-casein and whey acidic protein of rat and mouse, suggest that they may all meet this requirement. Fragments of the ovine β-lactoglobulin, murine whey acidic protein and rabbit β-casein genes have directed production of novel proteins in the milk of transgenic mice, sheep, rabbits and pigs. The proteins were biologically active and usually co-migrated with authentic proteins. In early experiments, protein concentration was low, but our recent observations suggest that fusion genes containing genomic clones direct production of concentrations of protein that are suitable for commercial exploitation. In the longer term, two approaches may offer the potential of more reliable expression. Control elements capable of directing expression that is independent of site of insertion of the gene, but dependent on the number of copies of the gene, have been identified for a small number of genes. The availability of such elements for the milk protein genes would increase the reliability of gene expression considerably. Alternatively, targeted mutation of genes may allow the insertion of coding sequences within an existing gene so avoiding position effects.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 47 (1991), S. 866-877 
    ISSN: 1420-9071
    Keywords: Transgenic mice ; microinjection ; recombinant DNA ; gene expression ; transcription factors ; chromatin ; homologous recombination ; episomal maintenance ; embryonic stem cells ; germ line ; position-effect ; mosaicism ; globin genes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract This chapter is an attempt to summarize some commonly accepted and some more subjective opinions about the regulation of transgene expression in laboratory animals. After a short historical introduction, I present some general notions regarding gene structure/function. The spotlight shifts then to the description of the most popular techniques for gene transfer, including the targeted gene replacement. The different approaches are briefly discussed in terms of intrinsic advantages and limitations regarding gene expression patterns. Furthermore, the role of enhancers, promoters and othercis-acting elements such as silencers and dominant control regions as well as their involvement in the chromatin on-off state are discussed on the basis of a specific example studied in our laboratory. The review concludes by presenting recent results and the new perspectives opening in the field of ‘surrogate’ (also called ‘reversed’) genetics. Some problems which remain to be solved both at the technical as well as at the social-ethical level are also briefly presented.
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