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  • 1
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    AID enzyme-induced hypermutation in an actively transcribed gene in fibroblasts (2002)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2002-06-18
    Description: Activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is indispensable for somatic hypermutation (SHM), class switch recombination, and gene conversion of immunoglobulin genes, which indicates a common molecular mechanism for these phenomena. Here we show that ectopic expression of AID alone can induce hypermutation in an artificial GFP substrate in NIH 3T3 murine fibroblast cells. The frequency of mutations was closely correlated with the level of transcription of the target gene, and the distribution of mutations in NIH 3T3 cells was similar to those of SHM in B lymphocytes. These results indicate that AID is sufficient for the generation of SHM in an actively transcribed gene in fibroblasts, as well as B cells, and that any of the required cofactors must be present in these fibroblasts.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoshikawa, Kiyotsugu -- Okazaki, Il-Mi -- Eto, Tomonori -- Kinoshita, Kazuo -- Muramatsu, Masamichi -- Nagaoka, Hitoshi -- Honjo, Tasuku -- New York, N.Y. -- Science. 2002 Jun 14;296(5575):2033-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12065838" target="_blank"〉PubMed〈/a〉
    Keywords: 3T3 Cells ; Animals ; B-Lymphocytes/physiology ; Base Sequence ; Cytidine Deaminase/genetics/*metabolism ; DNA/chemistry/genetics ; Genes, Reporter ; Green Fluorescent Proteins ; Luminescent Proteins/genetics/metabolism ; Mice ; Molecular Sequence Data ; *Mutation ; Nucleic Acid Conformation ; Point Mutation ; Recombinant Proteins/metabolism ; Somatic Hypermutation, Immunoglobulin ; Transcription, Genetic ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Genetic restriction of AIDS pathogenesis by an SDF-1 chemokine gene variant. ALIVE Study, Hemophilia Growth and Development Study (HGDS), Multicenter AIDS Cohort Study (MACS), Multicenter Hemophilia Cohort Study (MHCS), San Francisco City Cohort (SFCC) (1998)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1998-02-07
    Description: Stromal-derived factor (SDF-1) is the principal ligand for CXCR4, a coreceptor with CD4 for T lymphocyte cell line-tropic human immunodeficiency virus-type 1 (HIV-1). A common polymorphism, SDF1-3'A, was identified in an evolutionarily conserved segment of the 3' untranslated region of the SDF-1 structural gene transcript. In the homozygous state, SDF1-3'A/3'A delays the onset of acquired immunodeficiency syndrome (AIDS), according to a genetic association analysis of 2857 patients enrolled in five AIDS cohort studies. The recessive protective effect of SDF1-3'A was increasingly pronounced in individuals infected with HIV-1 for longer periods, was twice as strong as the dominant genetic restriction of AIDS conferred by CCR5 and CCR2 chemokine receptor variants in these populations, and was complementary with these mutations in delaying the onset of AIDS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winkler, C -- Modi, W -- Smith, M W -- Nelson, G W -- Wu, X -- Carrington, M -- Dean, M -- Honjo, T -- Tashiro, K -- Yabe, D -- Buchbinder, S -- Vittinghoff, E -- Goedert, J J -- O'Brien, T R -- Jacobson, L P -- Detels, R -- Donfield, S -- Willoughby, A -- Gomperts, E -- Vlahov, D -- Phair, J -- O'Brien, S J -- New York, N.Y. -- Science. 1998 Jan 16;279(5349):389-93.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Science Applications International Corporation (SAIC), National Cancer Institute, Frederick, MD 21702, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9430590" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/genetics/*immunology/virology ; Adult ; Chemokine CXCL12 ; Chemokines/chemistry/*genetics/physiology ; *Chemokines, CXC ; Cohort Studies ; Continental Population Groups ; Disease Progression ; Genes ; Genetic Variation ; Genotype ; HIV Infections/genetics/*immunology/virology ; HIV-1/*physiology ; Heterozygote ; Humans ; Male ; Molecular Sequence Data ; Odds Ratio ; Polymorphism, Genetic ; Receptors, CCR2 ; Receptors, CCR5/genetics/physiology ; Receptors, CXCR4/metabolism ; Receptors, Chemokine/genetics/physiology ; Survival Analysis ; T-Lymphocytes/virology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
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    Generation of lymphohematopoietic cells from embryonic stem cells in culture (1994)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1994-08-19
    Description: An efficient system was developed that induced the differentiation of embryonic stem (ES) cells into blood cells of erythroid, myeloid, and B cell lineages by coculture with the stromal cell line OP9. This cell line does not express functional macrophage colony-stimulating factor (M-CSF). The presence of M-CSF had inhibitory effects on the differentiation of ES cells to blood cells other than macrophages. Embryoid body formation or addition of exogenous growth factors was not required, and differentiation was highly reproducible even after the selection of ES cells with the antibiotic G418. Combined with the ability to genetically manipulate ES cells, this system will facilitate the study of molecular mechanisms involved in development and differentiation of hematopoietic cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nakano, T -- Kodama, H -- Honjo, T -- New York, N.Y. -- Science. 1994 Aug 19;265(5175):1098-101.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Chemistry, Faculty of Medicine, Kyoto University Yoshida, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8066449" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/cytology ; Base Sequence ; Cell Differentiation ; Cell Line ; Cells, Cultured ; Culture Media ; Erythrocytes/cytology ; Erythropoiesis ; Gene Rearrangement ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology ; Lymphocytes/*cytology ; Macrophage Colony-Stimulating Factor/pharmacology ; Macrophages/cytology ; Mesoderm/cytology ; Mice ; Molecular Sequence Data ; Recombinant Proteins/pharmacology ; Stromal Cells/cytology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 4
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    Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins (1993)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1993-07-30
    Description: A method was developed to clone, without the use of specific functional assays, complementary DNAs (cDNAs) that carry specific amino-terminal signal sequences, such as those encoding intercellular signal-transducing molecules and receptors. The vector used in this system directed the cell surface expression of interleukin-2 receptor fusion proteins when inserts with signal sequences were cloned in-frame with the correct orientation. An expression cDNA library was constructed from a bone marrow stromal cell line, which contained 5' portion-enriched cDNAs (the average size was 400 base pairs). Two cDNAs that encoded putative cytokine molecules, stromal cell-derived factor-1 alpha (SDF-1 alpha) and SDF-1 beta, which belong to the intercrine-macrophage inflammatory protein superfamily, were cloned.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tashiro, K -- Tada, H -- Heilker, R -- Shirozu, M -- Nakano, T -- Honjo, T -- New York, N.Y. -- Science. 1993 Jul 30;261(5121):600-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/8342023" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Base Sequence ; Cell Line ; Chemokine CXCL12 ; *Chemokines, CXC ; Cloning, Molecular/*methods ; Cytokines/chemistry/*genetics ; Genetic Vectors ; Molecular Sequence Data ; Open Reading Frames ; Protein Sorting Signals/chemistry/*genetics/metabolism ; Receptors, Interleukin-2/genetics ; Recombinant Fusion Proteins/biosynthesis ; Transfection
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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