This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zweidler-Mckay, P. A.
Right arrow Articles by Tsichlis, P. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zweidler-Mckay, P. A.
Right arrow Articles by Tsichlis, P. N.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Aug 1996, 4024-4034, Vol 16, No. 8
Copyright © 1996, American Society for Microbiology

Gfi-1 encodes a nuclear zinc finger protein that binds DNA and functions as a transcriptional repressor

PA Zweidler-Mckay, HL Grimes, MM Flubacher and PN Tsichlis
Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.

The Gfi-1 proto-oncogene encodes a zinc finger protein with six C2H2- type, C-terminal zinc finger motifs and is activated by provirus integration in T-cell lymphoma lines selected for interleukin-2 independence in culture and in primary retrovirus-induced thymomas. Gfi- 1 expression in adult animals is restricted to the thymus, spleen, and testis and is enhanced in mitogen-stimulated splenocytes. In this report, we show that Gfi-1 is a 55-kDa nuclear protein that binds DNA in a sequence-specific manner. The Gfi-1 binding site, TAAATCAC(A/T)GCA, was defined via random oligonucleotide selection utilizing a bacterially expressed glutathione S-transferase-Gfi-1 fusion protein. Binding to this site was confirmed by electrophoretic mobility shift assays and DNase I footprinting. Methylation interference analysis and electrophoretic mobility shift assays with mutant oliginucleotides defined the relative importance of specific bases at the consensus binding site. Deletion of individual zinc fingers demonstrated that only zinc fingers 3, 4, and 5 are required for sequence-specific DNA binding. Potential Gfi-1 binding sites were detected in a large number of eukaryotic promoter-enhancers, including the enhancers of several proto-oncogenes and cytokine genes and the enhancer of the human cytomegalovirus (HCMV) major immediate-early promoter, which contains two such sites. HCMV major immediate-early- chloramphenicol acetyltransferase reporter constructs, transfected into NIH 3T3 fibroblasts, were repressed by Gfi-1, and the repression was abrogated by mutation of critical residues in the two Gfi-1 binding sites. These results suggest that Gfi-1 may play a role in HCMV biology and may contribute to oncogenesis and T-cell activation by repressing the expression of genes that inhibit these processes.


This article has been cited by other articles:

  • Ichiyama, K., Hashimoto, M., Sekiya, T., Nakagawa, R., Wakabayashi, Y., Sugiyama, Y., Komai, K., Saba, I., Moroy, T., Yoshimura, A. (2009). Gfi1 negatively regulates Th17 differentiation by inhibiting ROR{gamma}t activity. Int Immunol 21: 881-889 [Abstract] [Full Text]  
  • Horman, S. R., Velu, C. S., Chaubey, A., Bourdeau, T., Zhu, J., Paul, W. E., Gebelein, B., Grimes, H. L. (2009). Gfi1 integrates progenitor versus granulocytic transcriptional programming. Blood 113: 5466-5475 [Abstract] [Full Text]  
  • Zhu, J., Davidson, T. S., Wei, G., Jankovic, D., Cui, K., Schones, D. E., Guo, L., Zhao, K., Shevach, E. M., Paul, W. E. (2009). Down-regulation of Gfi-1 expression by TGF-{beta} is important for differentiation of Th17 and CD103+ inducible regulatory T cells. JEM 206: 329-341 [Abstract] [Full Text]  
  • Montoya-Durango, D. E., Velu, C. S., Kazanjian, A., Rojas, M. E. B., Jay, C. M., Longmore, G. D., Grimes, H. L. (2008). Ajuba Functions as a Histone Deacetylase-dependent Co-repressor for Autoregulation of the Growth Factor-independent-1 Transcription Factor. J. Biol. Chem. 283: 32056-32065 [Abstract] [Full Text]  
  • Shinnakasu, R., Yamashita, M., Kuwahara, M., Hosokawa, H., Hasegawa, A., Motohashi, S., Nakayama, T. (2008). Gfi1-mediated Stabilization of GATA3 Protein Is Required for Th2 Cell Differentiation. J. Biol. Chem. 283: 28216-28225 [Abstract] [Full Text]  
  • Hou, Z., Peng, H., Ayyanathan, K., Yan, K.-P., Langer, E. M., Longmore, G. D., Rauscher, F. J. III (2008). The LIM Protein AJUBA Recruits Protein Arginine Methyltransferase 5 To Mediate SNAIL-Dependent Transcriptional Repression. Mol. Cell. Biol. 28: 3198-3207 [Abstract] [Full Text]  
  • Chandele, A., Joshi, N. S., Zhu, J., Paul, W. E., Leonard, W. J., Kaech, S. M. (2008). Formation of IL-7R{alpha}high and IL-7R{alpha}low CD8 T Cells during Infection Is Regulated by the Opposing Functions of GABP{alpha} and Gfi-1. J. Immunol. 180: 5309-5319 [Abstract] [Full Text]  
  • Xie, B., Charlton-Perkins, M., McDonald, E., Gebelein, B., Cook, T. (2007). Senseless functions as a molecular switch for color photoreceptor differentiation in Drosophila. Development 134: 4243-4253 [Abstract] [Full Text]  
  • Ayyanathan, K., Peng, H., Hou, Z., Fredericks, W. J., Goyal, R. K., Langer, E. M., Longmore, G. D., Rauscher, F. J. III (2007). The Ajuba LIM Domain Protein Is a Corepressor for SNAG Domain Mediated Repression and Participates in Nucleocytoplasmic Shuttling. Cancer Res. 67: 9097-9106 [Abstract] [Full Text]  
  • Duan, Z., Person, R. E., Lee, H.-H., Huang, S., Donadieu, J., Badolato, R., Grimes, H. L., Papayannopoulou, T., Horwitz, M. S. (2007). Epigenetic Regulation of Protein-Coding and MicroRNA Genes by the Gfi1-Interacting Tumor Suppressor PRDM5. Mol. Cell. Biol. 27: 6889-6902 [Abstract] [Full Text]  
  • Kuo, Y.-Y., Chang, Z.-F. (2007). GATA-1 and Gfi-1B Interplay To Regulate Bcl-xL Transcription. Mol. Cell. Biol. 27: 4261-4272 [Abstract] [Full Text]  
  • Vassen, L., Okayama, T., Moroy, T. (2007). Gfi1b:green fluorescent protein knock-in mice reveal a dynamic expression pattern of Gfi1b during hematopoiesis that is largely complementary to Gfi1. Blood 109: 2356-2364 [Abstract] [Full Text]  
  • Dahl, R., Iyer, S. R., Owens, K. S., Cuylear, D. D., Simon, M. C. (2007). The Transcriptional Repressor GFI-1 Antagonizes PU.1 Activity through Protein-Protein Interaction. J. Biol. Chem. 282: 6473-6483 [Abstract] [Full Text]  
  • Marteijn, J. A. F., van der Meer, L. T., Van Emst, L., de Witte, T., Jansen, J. H., van der Reijden, B. A. (2007). Diminished proteasomal degradation results in accumulation of Gfi1 protein in monocytes. Blood 109: 100-108 [Abstract] [Full Text]  
  • Sinclair, J., Sissons, P. (2006). Latency and reactivation of human cytomegalovirus. J. Gen. Virol. 87: 1763-1779 [Abstract] [Full Text]  
  • Acar, M., Jafar-Nejad, H., Giagtzoglou, N., Yallampalli, S., David, G., He, Y., Delidakis, C., Bellen, H. J. (2006). Senseless physically interacts with proneural proteins and functions as a transcriptional co-activator. Development 133: 1979-1989 [Abstract] [Full Text]  
  • Jafar-Nejad, H., Tien, A.-C., Acar, M., Bellen, H. J. (2006). Senseless and Daughterless confer neuronal identity to epithelial cells in the Drosophila wing margin. Development 133: 1683-1692 [Abstract] [Full Text]  
  • Zhuang, D., Qiu, Y., Kogan, S. C., Dong, F. (2006). Increased CCAAT Enhancer-binding Protein {epsilon} (C/EBP{epsilon}) Expression and Premature Apoptosis in Myeloid Cells Expressing Gfi-1 N382S Mutant Associated with Severe Congenital Neutropenia. J. Biol. Chem. 281: 10745-10751 [Abstract] [Full Text]  
  • Duan, Z., Zarebski, A., Montoya-Durango, D., Grimes, H. L., Horwitz, M. (2005). Gfi1 Coordinates Epigenetic Repression of p21Cip/WAF1 by Recruitment of Histone Lysine Methyltransferase G9a and Histone Deacetylase 1. Mol. Cell. Biol. 25: 10338-10351 [Abstract] [Full Text]  
  • Huang, D.-Y., Kuo, Y.-Y., Chang, Z.-F. (2005). GATA-1 mediates auto-regulation of Gfi-1B transcription in K562 cells. Nucleic Acids Res 33: 5331-5342 [Abstract] [Full Text]  
  • Dwivedi, P. P, Anderson, P. H, Omdahl, J. L, Grimes, H L., Morris, H. A, May, B. K (2005). Identification of growth factor independent-1 (GFI1) as a repressor of 25-hydroxyvitamin D 1-alpha hydroxylase (CYP27B1) gene expression in human prostate cancer cells. Endocr Relat Cancer 12: 351-365 [Abstract] [Full Text]  
  • Reeves, M. B., MacAry, P. A., Lehner, P. J., Sissons, J. G. P., Sinclair, J. H. (2005). Latency, chromatin remodeling, and reactivation of human cytomegalovirus in the dendritic cells of healthy carriers. Proc. Natl. Acad. Sci. USA 102: 4140-4145 [Abstract] [Full Text]  
  • Wright, E., Bain, M., Teague, L., Murphy, J., Sinclair, J. (2005). Ets-2 repressor factor recruits histone deacetylase to silence human cytomegalovirus immediate-early gene expression in non-permissive cells. J. Gen. Virol. 86: 535-544 [Abstract] [Full Text]  
  • Vassen, L., Fiolka, K., Mahlmann, S., Möröy, T. (2005). Direct transcriptional repression of the genes encoding the zinc-finger proteins Gfi1b and Gfi1 by Gfi1b. Nucleic Acids Res 33: 987-998 [Abstract] [Full Text]  
  • Garcon, L., Lacout, C., Svinartchouk, F., Le Couedic, J.-P., Villeval, J.-L., Vainchenker, W., Dumenil, D. (2005). Gfi-1B plays a critical role in terminal differentiation of normal and transformed erythroid progenitor cells. Blood 105: 1448-1455 [Abstract] [Full Text]  
  • Yap, Y. L., Wong, M. P., Zhang, X. W., Hernandez, D., Gras, R., Smith, D. K., Danchin, A. (2005). Conserved transcription factor binding sites of cancer markers derived from primary lung adenocarcinoma microarrays. Nucleic Acids Res 33: 409-421 [Abstract] [Full Text]  
  • Jafar-Nejad, H., Bellen, H. J. (2004). Gfi/Pag-3/Senseless Zinc Finger Proteins: a Unifying Theme?. Mol. Cell. Biol. 24: 8803-8812 [Full Text]  
  • Kazanjian, A., Wallis, D., Au, N., Nigam, R., Venken, K. J. T., Cagle, P. T., Dickey, B. F., Bellen, H. J., Gilks, C. B., Grimes, H. L. (2004). Growth Factor Independence-1 Is Expressed in Primary Human Neuroendocrine Lung Carcinomas and Mediates the Differentiation of Murine Pulmonary Neuroendocrine Cells. Cancer Res. 64: 6874-6882 [Abstract] [Full Text]  
  • Yucel, R., Kosan, C., Heyd, F., Moroy, T. (2004). Gfi1:Green Fluorescent Protein Knock-in Mutant Reveals Differential Expression and Autoregulation of the Growth Factor Independence 1 (Gfi1) Gene during Lymphocyte Development. J. Biol. Chem. 279: 40906-40917 [Abstract] [Full Text]  
  • Hertzano, R., Montcouquiol, M., Rashi-Elkeles, S., Elkon, R., Yucel, R., Frankel, W. N., Rechavi, G., Moroy, T., Friedman, T. B., Kelley, M. W., Avraham, K. B. (2004). Transcription profiling of inner ears from Pou4f3ddl/ddl identifies Gfi1 as a target of the Pou4f3 deafness gene. Hum Mol Genet 13: 2143-2153 [Abstract] [Full Text]  
  • Huang, D.-Y., Kuo, Y.-Y., Lai, J.-S., Suzuki, Y., Sugano, S., Chang, Z.-F. (2004). GATA-1 and NF-Y cooperate to mediate erythroid-specific transcription of Gfi-1B gene. Nucleic Acids Res 32: 3935-3946 [Abstract] [Full Text]  
  • Doan, L. L., Porter, S. D., Duan, Z., Flubacher, M. M., Montoya, D., Tsichlis, P. N., Horwitz, M., Gilks, C. B., Grimes, H. L. (2004). Targeted transcriptional repression of Gfi1 by GFI1 and GFI1B in lymphoid cells. Nucleic Acids Res 32: 2508-2519 [Abstract] [Full Text]  
  • Frankfort, B. J., Mardon, G. (2004). Senseless represses nuclear transduction of Egfr pathway activation. Development 131: 563-570 [Abstract] [Full Text]  
  • Jafar-Nejad, H., Acar, M., Nolo, R., Lacin, H., Pan, H., Parkhurst, S. M., Bellen, H. J. (2003). Senseless acts as a binary switch during sensory organ precursor selection. Genes Dev. 17: 2966-2978 [Abstract] [Full Text]  
  • Chandrasekaran, V., Beckendorf, S. K. (2003). senseless is necessary for the survival of embryonic salivary glands in Drosophila. Development 130: 4719-4728 [Abstract] [Full Text]  
  • Ayyanathan, K., Lechner, M. S., Bell, P., Maul, G. G., Schultz, D. C., Yamada, Y., Tanaka, K., Torigoe, K., Rauscher, F. J. III (2003). Regulated recruitment of HP1 to a euchromatic gene induces mitotically heritable, epigenetic gene silencing: a mammalian cell culture model of gene variegation. Genes Dev. 17: 1855-1869 [Abstract] [Full Text]  
  • Duan, Z., Horwitz, M. (2003). Targets of the transcriptional repressor oncoprotein Gfi-1. Proc. Natl. Acad. Sci. USA 100: 5932-5937 [Abstract] [Full Text]  
  • Yucel, R., Karsunky, H., Klein-Hitpass, L., Moroy, T. (2003). The Transcriptional Repressor Gfi1 Affects Development of Early, Uncommitted c-Kit+ T Cell Progenitors and CD4/CD8 Lineage Decision in the Thymus. JEM 197: 831-844 [Abstract] [Full Text]  
  • Osawa, M., Yamaguchi, T., Nakamura, Y., Kaneko, S., Onodera, M., Sawada, K.-i., Jegalian, A., Wu, H., Nakauchi, H., Iwama, A. (2002). Erythroid expansion mediated by the Gfi-1B zinc finger protein: role in normal hematopoiesis. Blood 100: 2769-2777 [Abstract] [Full Text]  
  • Breslin, M. B., Zhu, M., Notkins, A. L., Lan, M. S. (2002). Neuroendocrine differentiation factor, IA-1, is a transcriptional repressor and contains a specific DNA-binding domain: identification of consensus IA-1 binding sequence. Nucleic Acids Res 30: 1038-1045 [Abstract] [Full Text]  
  • Saleque, S., Cameron, S., Orkin, S. H. (2002). The zinc-finger proto-oncogene Gfi-1b is essential for development of the erythroid and megakaryocytic lineages. Genes Dev. 16: 301-306 [Abstract] [Full Text]  
  • Cameron, S., Clark, S. G., McDermott, J. B., Aamodt, E., Horvitz, H. R. (2002). PAG-3, a Zn-finger transcription factor, determines neuroblast fate in C. elegans. Development 129: 1763-1774 [Abstract] [Full Text]  
  • Li, J.-H., Chia, M., Shi, W., Ngo, D., Strathdee, C. A., Huang, D., Klamut, H., Liu, F.-F. (2002). Tumor-targeted Gene Therapy for Nasopharyngeal Carcinoma. Cancer Res. 62: 171-178 [Abstract] [Full Text]  
  • Delany, A. M., Durant, D., Canalis, E. (2001). Glucocorticoid Suppression of IGF I Transcription in Osteoblasts. Mol. Endocrinol. 15: 1781-1789 [Abstract] [Full Text]  
  • Feral, C., Guellaen, G., Pawlak, A. (2001). Human testis expresses a specific poly(A)-binding protein. Nucleic Acids Res 29: 1872-1883 [Abstract] [Full Text]  
  • Mellott, J. K., Nick, H. S., Waters, M. F., Billiar, T. R., Geller, D. A., Chesrown, S. E. (2001). Cytokine-induced changes in chromatin structure and in vivo footprints in the inducible NOS promoter. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L390-L399 [Abstract] [Full Text]  
  • Mundt, C. A., Nicholson, I. C., Zou, X., Popov, A. V., Ayling, C., Bruggemann, M. (2001). Novel Control Motif Cluster in the IgH {{delta}}-{{gamma}}3 Interval Exhibits B Cell-Specific Enhancer Function in Early Development. J. Immunol. 166: 3315-3323 [Abstract] [Full Text]  
  • Meier, J. L. (2001). Reactivation of the Human Cytomegalovirus Major Immediate-Early Regulatory Region and Viral Replication in Embryonal NTera2 Cells: Role of Trichostatin A, Retinoic Acid, and Deletion of the 21-Base-Pair Repeats and Modulator. J. Virol. 75: 1581-1593 [Abstract] [Full Text]  
  • Tateno, M., Fukunishi, Y., Komatsu, S., Okazaki, Y., Kawai, J., Shibata, K., Itoh, M., Muramatsu, M., Held, W. A., Hayashizaki, Y. (2001). Identification of a Novel Member of the Snail/Gfi-1 Repressor Family, mlt 1, Which Is Methylated and Silenced in Liver Tumors of SV40 T Antigen Transgenic Mice. Cancer Res. 61: 1144-1153 [Abstract] [Full Text]  
  • Meier, J. L., Pruessner, J. A. (2000). The Human Cytomegalovirus Major Immediate-Early Distal Enhancer Region Is Required for Efficient Viral Replication and Immediate-Early Gene Expression. J. Virol. 74: 1602-1613 [Abstract] [Full Text]  
  • Ma, L, Merenmies, J, Parada, L. (2000). Molecular characterization of the TrkA/NGF receptor minimal enhancer reveals regulation by multiple cis elements to drive embryonic neuron expression. Development 127: 3777-3788 [Abstract]  
  • Lundquist, C. A., Meier, J. L., Stinski, M. F. (1999). A Strong Negative Transcriptional Regulatory Region between the Human Cytomegalovirus UL127 Gene and the Major Immediate-Early Enhancer. J. Virol. 73: 9039-9052 [Abstract] [Full Text]  
  • Sinn, P. L., Zhang, X., Sigmund, C. D. (1999). JG cell expression and partial regulation of a human renin genomic transgene driven by a minimal renin promoter. Am. J. Physiol. Renal Physiol. 277: F634-F642 [Abstract] [Full Text]  
  • Iuchi, S., Green, H. (1999). Basonuclin, a zinc finger protein of keratinocytes and reproductive germ cells, binds to the rRNA gene promoter. Proc. Natl. Acad. Sci. USA 96: 9628-9632 [Abstract] [Full Text]  
  • Nicol, R., Zheng, G., Sutrave, P., Foster, D. N., Stavnezer, E. (1999). Association of Specific DNA Binding and Transcriptional Repression with the Transforming and Myogenic Activities of c-Ski. Cell Growth Differ. 10: 243-254 [Abstract] [Full Text]  
  • Varrault, A., Ciani, E., Apiou, F., Bilanges, B., Hoffmann, A., Pantaloni, C., Bockaert, J., Spengler, D., Journot, L. (1998). hZAC encodes a zinc finger protein with antiproliferative properties and maps to a chromosomal region frequently lost in cancer. Proc. Natl. Acad. Sci. USA 95: 8835-8840 [Abstract] [Full Text]  
  • Tong, B., Grimes, H. L., Yang, T.-Y., Bear, S. E., Qin, Z., Du, K., El-Deiry, W. S., Tsichlis, P. N. (1998). The Gfi-1B Proto-Oncoprotein Represses p21WAF1 and Inhibits Myeloid Cell Differentiation. Mol. Cell. Biol. 18: 2462-2473 [Abstract] [Full Text]  
  • Adachi, K., Saito, H., Tanaka, T., Oka, T. (1998). Molecular Cloning and Characterization of the Murine Staf cDNA Encoding a Transcription Activating Factor for the Selenocysteine tRNA Gene in Mouse Mammary Gland. J. Biol. Chem. 273: 8598-8606 [Abstract] [Full Text]  
  • Tsatsanis, C., Patriotis, C., Bear, S. E., Tsichlis, P. N. (1998). The Tpl-2 protooncoprotein activates the nuclear factor of activated T cells and induces interleukin 2 expression in T cell lines. Proc. Natl. Acad. Sci. USA 95: 3827-3832 [Abstract] [Full Text]  
  • Hahm, K., Cobb, B. S., McCarty, A. S., Brown, K. E., Klug, C. A., Lee, R., Akashi, K., Weissman, I. L., Fisher, A. G., Smale, S. T. (1998). Helios, a T cell-restricted Ikaros family member that quantitatively associates with Ikaros at centromeric heterochromatin. Genes Dev. 12: 782-796 [Abstract] [Full Text]  
  • Yet, S.-F., McA'Nulty, M. M., Folta, S. C., Yen, H.-W., Yoshizumi, M., Hsieh, C.-M., Layne, M. D., Chin, M. T., Wang, H., Perrella, M. A., Jain, M. K., Lee, M.-E. (1998). Human EZF, a Kruppel-like Zinc Finger Protein, Is Expressed in Vascular Endothelial Cells and Contains Transcriptional Activation and Repression Domains. J. Biol. Chem. 273: 1026-1031 [Abstract] [Full Text]  
  • Jahnen-Dechent, W., Schinke, T., Trindl, A., Muller-Esterl, W., Sablitzky, F., Kaiser, S., Blessing, M. (1997). Cloning and Targeted Deletion of the Mouse Fetuin Gene. J. Biol. Chem. 272: 31496-31503 [Abstract] [Full Text]  
  • Greisman, H. A., Pabo, C. O. (1997). A General Strategy for Selecting High-Affinity Zinc Finger Proteins for Diverse DNA Target Sites. Science 275: 657-661 [Abstract] [Full Text]  
  • Jia, Y, Xie, G, McDermott, J., Aamodt, E (1997). The C. elegans gene pag-3 is homologous to the zinc finger proto-oncogene gfi-1. Development 124: 2063-2073 [Abstract]  
  • Grimes, H. L., Gilks, C. B., Chan, T. O., Porter, S., Tsichlis, P. N. (1996). The Gfi-1 protooncoprotein represses Bax expression and inhibits T-cell death. Proc. Natl. Acad. Sci. USA 93: 14569-14573 [Abstract] [Full Text]  
  • Perdomo, J., Holmes, M., Chong, B., Crossley, M. (2000). Eos and Pegasus, Two Members of the Ikaros Family of Proteins with Distinct DNA Binding Activities. J. Biol. Chem. 275: 38347-38354 [Abstract] [Full Text]  
  • Dreier, B., Beerli, R. R., Segal, D. J., Flippin, J. D., Barbas, C. F. III (2001). Development of Zinc Finger Domains for Recognition of the 5'-ANN-3' Family of DNA Sequences and Their Use in the Construction of Artificial Transcription Factors. J. Biol. Chem. 276: 29466-29478 [Abstract] [Full Text]  
  • Jegalian, A. G., Wu, H. (2002). Regulation of Socs Gene Expression by the Proto-oncoprotein GFI-1B. TWO ROUTES FOR STAT5 TARGET GENE INDUCTION BY ERYTHROPOIETIN. J. Biol. Chem. 277: 2345-2352 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»