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2006

Genetics and Genomics

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Activated Checkpoint Kinase 2 Provides A Survival Signal For Tumor Cells, Jagadish C. Ghosh, Takehiko Dohi, Christopher M. Raskett, Timothy F. Kowalik, Dario C. Altieri Dec 2006

Activated Checkpoint Kinase 2 Provides A Survival Signal For Tumor Cells, Jagadish C. Ghosh, Takehiko Dohi, Christopher M. Raskett, Timothy F. Kowalik, Dario C. Altieri

Open Access Articles

Tumor cells often become resistant to DNA damage-based therapy; however, the underlying mechanisms are not yet understood. Here, we show that tumor cells exposed to DNA damage counteract cell death by releasing the antiapoptotic protein, survivin, from mitochondria. This is independent of p53, and requires activated checkpoint kinase 2 (Chk2), a putative tumor suppressor. Molecular or genetic targeting of Chk2 prevents the release of survivin from mitochondria, enhances DNA damage-induced tumor cell apoptosis, and inhibits the growth of resistant in vivo tumors. Therefore, activated Chk2 circumvents its own tumor-suppressive functions by promoting tumor cell survival. Inhibiting Chk2 in combination with ...


Cbfbeta Reduces Cbfbeta-Smmhc-Associated Acute Myeloid Leukemia In Mice, Susan Ann Heilman, Ya-Huei Kuo, Chantal S. Goudswaard, Peter J. Valk, Lucio H. Castilla Dec 2006

Cbfbeta Reduces Cbfbeta-Smmhc-Associated Acute Myeloid Leukemia In Mice, Susan Ann Heilman, Ya-Huei Kuo, Chantal S. Goudswaard, Peter J. Valk, Lucio H. Castilla

Open Access Articles

The gene encoding for core-binding factor beta (CBFbeta) is altered in acute myeloid leukemia samples with an inversion in chromosome 16, expressing the fusion protein CBFbeta-SMMHC. Previous studies have shown that this oncoprotein interferes with hematopoietic differentiation and proliferation and participates in leukemia development. In this study, we provide evidence that Cbfbeta modulates the oncogenic function of this fusion protein. We show that Cbfbeta plays an important role in proliferation of hematopoietic progenitors expressing Cbfbeta-SMMHC in vitro. In addition, Cbfbeta-SMMHC-mediated leukemia development is accelerated in the absence of Cbfbeta. These results indicate that the balance between Cbfbeta and Cbfbeta-SMMHC directly ...


Trefoil Family Factor 2 Is Expressed In Murine Gastric And Immune Cells And Controls Both Gastrointestinal Inflammation And Systemic Immune Responses, Evelyn A. Kurt-Jones, Lucheng Cao, Frantisek Sandor, Arlin B. Rogers, Mark T. Whary, Prashant R. Nambiar, Anna M. Cerny, Glennice N. Bowen, Jing Yan, Shigeo Takaishi, Alfred L. Chi, George W. Reed, Jeanmarie Houghton, James G. Fox, Timothy C. Wang Nov 2006

Trefoil Family Factor 2 Is Expressed In Murine Gastric And Immune Cells And Controls Both Gastrointestinal Inflammation And Systemic Immune Responses, Evelyn A. Kurt-Jones, Lucheng Cao, Frantisek Sandor, Arlin B. Rogers, Mark T. Whary, Prashant R. Nambiar, Anna M. Cerny, Glennice N. Bowen, Jing Yan, Shigeo Takaishi, Alfred L. Chi, George W. Reed, Jeanmarie Houghton, James G. Fox, Timothy C. Wang

Open Access Articles

Trefoil family factor 2 (TFF2), also known as spasmolytic peptide, is a low-molecular-weight protein that is upregulated in gastric tissues infected with Helicobacter or having other inflammatory conditions, but a precise function is yet to be elucidated. The role of TFF2 in the development of gastritis, colitis, and inflammatory cytokine responses was examined both in vivo and in vitro using wild-type and TFF2 knockout mice. TFF2 knockout and wild-type mice were infected with Helicobacter felis (H. felis) to induce gastritis. Colitis was induced in TFF2 knockout and wild-type mice by administering dextran sodium sulfate (DSS) in drinking water. Histopathology, clinical ...


Chromosome Conformation Capture Carbon Copy (5c): A Massively Parallel Solution For Mapping Interactions Between Genomic Elements, Josee Dostie, Todd A. Richmond, Ramy A. Arnaout, Rebecca R. Selzer, William L. Lee, Tracey A. Honan, Eric D. Rubio, Anton Krumm, Justin Lamb, Chad Nusbaum, Roland D. Green, Job Dekker Oct 2006

Chromosome Conformation Capture Carbon Copy (5c): A Massively Parallel Solution For Mapping Interactions Between Genomic Elements, Josee Dostie, Todd A. Richmond, Ramy A. Arnaout, Rebecca R. Selzer, William L. Lee, Tracey A. Honan, Eric D. Rubio, Anton Krumm, Justin Lamb, Chad Nusbaum, Roland D. Green, Job Dekker

Open Access Articles

Physical interactions between genetic elements located throughout the genome play important roles in gene regulation and can be identified with the Chromosome Conformation Capture (3C) methodology. 3C converts physical chromatin interactions into specific ligation products, which are quantified individually by PCR. Here we present a high-throughput 3C approach, 3C-Carbon Copy (5C), that employs microarrays or quantitative DNA sequencing using 454-technology as detection methods. We applied 5C to analyze a 400-kb region containing the human beta-globin locus and a 100-kb conserved gene desert region. We validated 5C by detection of several previously identified looping interactions in the beta-globin locus. We also ...


From Imaging To Understanding: Frontiers In Live Cell Imaging, Bethesda, Md, April 19-21, 2006, Yu-Li Wang, Klaus M. Hahn, Robert F. Murphy, Alan F. Horwitz Aug 2006

From Imaging To Understanding: Frontiers In Live Cell Imaging, Bethesda, Md, April 19-21, 2006, Yu-Li Wang, Klaus M. Hahn, Robert F. Murphy, Alan F. Horwitz

Open Access Articles

No abstract provided.


The Active Fmr1 Promoter Is Associated With A Large Domain Of Altered Chromatin Conformation With Embedded Local Histone Modifications, Nele Gheldof, Tomoko M. Tabuchi, Job Dekker Aug 2006

The Active Fmr1 Promoter Is Associated With A Large Domain Of Altered Chromatin Conformation With Embedded Local Histone Modifications, Nele Gheldof, Tomoko M. Tabuchi, Job Dekker

Open Access Articles

We have analyzed the effects of gene activation on chromatin conformation throughout an approximately 170-kb region comprising the human fragile X locus, which includes a single expressed gene, FMR1 (fragile X mental retardation 1). We have applied three approaches: (i) chromosome conformation capture, which assesses relative interaction frequencies of chromatin segments; (ii) an extension of this approach that identifies domains whose conformation differs from the average, which we developed and named chromosome conformation profiling; and (iii) ChIP analysis of histone modifications. We find that, in normal cells where FMR1 is active, the FMR1 promoter is at the center of a ...


Linkage Analysis Of Longitudinal Data And Design Consideration, Heping Zhang, Xiaoyun Zhong Jun 2006

Linkage Analysis Of Longitudinal Data And Design Consideration, Heping Zhang, Xiaoyun Zhong

Open Access Articles

BACKGROUND: Statistical methods have been proposed recently to analyze longitudinal data in genetic studies. So far, little attention has been paid to examine the relationship among key factors in genetic longitudinal studies including power, the number of families or sibships, and the number of repeated measures per individual subjects.

RESULTS: We proposed a variance component model that extends classic variance component models for a single quantitative trait to mapping longitudinal traits. Our model includes covariate effects and allows genetic effects to vary over time. Using our proposed model, we examined the power, pedigree structures, and sample size through simulation experiments ...


Mitosis-Independent Survivin Gene Expression In Vivo And Regulation By P53, Fang Xia, Dario C. Altieri Apr 2006

Mitosis-Independent Survivin Gene Expression In Vivo And Regulation By P53, Fang Xia, Dario C. Altieri

Open Access Articles

Survivin is an essential mitotic gene, and this has been speculated to reflect its primary function in development and cancer. Here, we generated a knock-in transgenic mouse (SVVp-GFP) in which a green fluorescent protein (GFP) reporter gene was placed under the control of the survivin promoter that regulates transcription at mitosis. The expression of endogenous survivin was widespread in mouse tissues during development and shortly after birth. In contrast, GFP reactivity was undetectable in transgenic mouse embryos, and was largely limited postnatally to mitotic cells in the testes. Double transgenic mice generated in the tumor-prone Min/+ background exhibited intestinal adenomas ...


Towards The Visualization Of Genome Activity At Nanoscale Dimensions, Joan C. Ritland Politz Mar 2006

Towards The Visualization Of Genome Activity At Nanoscale Dimensions, Joan C. Ritland Politz

Open Access Articles

No abstract provided.