Sat, 26 Jul 2008 17:18:42 BST CiteULike: jyuh Sedivy http://www.citeulike.org/user/jyuh/author/Sedivy CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/jyuh/article/2789321 <i>BMC bioinformatics, Vol. 9 Suppl 4 (2008)</i><br /><br />BACKGROUND: Significance analysis at single gene level may suffer from the limited number of samples and experimental noise that can severely limit the power of the chosen statistical test. This problem is typically approached by applying post hoc corrections to control the false discovery rate, without taking into account prior biological knowledge. Pathway or gene ontology analysis can provide an alternative way to relax the significance threshold applied to single genes and may lead to a better biological interpretation. RESULTS: Here we propose a new analysis method based on the study of networks of pathways. These networks are reconstructed considering both the significance of single pathways (network nodes) and the intersection between them (links).We apply this method for the reconstruction of networks of pathways to two gene expression datasets: the first one obtained from a c-Myc rat fibroblast cell line expressing a conditional Myc-estrogen receptor oncoprotein; the second one obtained from the comparison of Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia derived from bone marrow samples. CONCLUSION: Our method extends statistical models that have been recently adopted for the significance analysis of functional groups of genes to infer links between these groups. We show that groups of genes at the interface between different pathways can be considered as relevant even if the pathways they belong to are not significant by themselves. Reconstructing networks of pathways via significance analysis of their intersections. M Francesconi D Remondini N Neretti JM Sedivy LN Cooper E Verondini L Milanesi G Castellani doi:10.1186/1471-2105-9-S4-S9 BMC bioinformatics, Vol. 9 Suppl 4 (2008) 2008-05-12T12:06:10-00:00 2008 BMC bioinformatics 1471-2105 9 Suppl 4 no-tag http://www.citeulike.org/user/jyuh/article/2784510 <i>Methods (San Diego, Calif.), Vol. 41, No. 2. (February 2007), pp. 143-150.</i><br /><br />Fluorescence activated cell sorting (FACS) analysis has become a standard tool to analyze cell cycle distributions in populations of cells. These methods require relatively large numbers of cells, and do not provide optimal resolution of the transitions between cell cycle phases. In this report we describe in detail complementary methods that utilize the incorporation of nucleotide analogs combined with microscopic examination. While often more time consuming, these protocols typically require far fewer cells, and allow accurate kinetic assessment of cell cycle progression. We also describe the use of a technique for the synchronization of adherent cells in mitosis by simple mechanical agitation (mitotic shake-off) that eliminates physiological perturbation associated with drug treatments. Analysis of cell cycle phases and progression in cultured mammalian cells. C Schorl JM Sedivy doi:10.1016/j.ymeth.2006.07.022 Methods (San Diego, Calif.), Vol. 41, No. 2. (February 2007), pp. 143-150. 2008-05-11T14:42:58-00:00 2007 Methods (San Diego, Calif.) 1046-2023 41 2 143 150 no-tag http://www.citeulike.org/user/jyuh/article/2481490 <i>Cell Signal, Vol. 20, No. 1. (January 2008), pp. 1-9.</i><br /><br />The Raf kinase inhibitory protein 1 (RKIP-1) and its orthologs are conserved throughout evolution and widely expressed in eukaryotic organisms. In its non-phosphorylated form RKIP-1 negatively regulates the Raf/MEK/ERK pathway by interfering with the activity of Raf-1. In its phosphorylated state, RKIP-1 dissociates from Raf-1 and inhibits GRK-2, a negative regulator of G-protein coupled receptors (GPCRs). Available data indicate that the phosphorylation of RKIP-1 by PKC can stimulate both the Raf/MEK/ERK and GPCR pathways. RKIP-1 has also been implicated as a negative regulator of the NF-kappaB pathway. Recent studies have shown that phosphorylated RKIP-1 binds to the centrosomal and kinetochore regions of metaphase chromosomes, where it may be involved in regulating the partitioning of chromosomes and the progression through mitosis. The collective evidence indicates that RKIP-1 regulates the activity and mediates the crosstalk between several important cellular signaling pathways. A variety of ablative interventions suggest that reduced RKIP-1 function may influence metastasis, angiogenesis, resistance to apoptosis, and genome integrity. Attenuation of RKIP-1 may also affect cardiac and neurological functions, spermatogenesis, sperm decapacitation, and reproductive behavior. In this review, the role of RKIP-1 in cellular signaling, and especially its functions revealed using a mouse knockout model, are discussed. Signaling crossroads: the function of Raf kinase inhibitory protein in cancer, the central nervous system and reproduction. J Klysik SJ Theroux JM Sedivy JS Moffit K Boekelheide doi:10.1016/j.cellsig.2007.07.003 Cell Signal, Vol. 20, No. 1. (January 2008), pp. 1-9. 2008-03-07T03:07:25-00:00 2008 Cell Signal 0898-6568 20 1 1 9 no-tag http://www.citeulike.org/user/jyuh/article/1686514 <i>Mech Ageing Dev, Vol. 127, No. 1. (January 2006), pp. 16-24.</i><br /><br />After a limited number of divisions, most eukaryotic cells grown in culture will undergo a terminal growth arrest called cellular senescence. This growth arrest is thought to be a consequence of progressive telomere shortening that occurs due to incomplete DNA replication of the chromosome ends. In addition, cellular senescence can also be induced by a number of environmental stresses and signaling imbalances which are independent of telomere shortening. The cyclin dependent kinase inhibitors p21 and p16(INK4a) have been shown to execute and maintain the cell cycle arrest in senescence but the nature of the signals that cause upregulation of these inhibitors in senescent cells are only now starting to be discovered. Here we will review the current literature that leads us to propose a model how independent signals activate distinct signaling pathways to regulate p21 and p16(INK4a) levels in senescent cells. Regulation of growth arrest in senescence: telomere damage is not the end of the story. U Herbig JM Sedivy doi:10.1016/j.mad.2005.09.002 Mech Ageing Dev, Vol. 127, No. 1. (January 2006), pp. 16-24. 2007-09-23T07:04:34-00:00 2006 Mech Ageing Dev 0047-6374 127 1 16 24 no-tag http://www.citeulike.org/user/jyuh/article/1447714 <i>Methods, Vol. 41, No. 2. (February 2007), pp. 143-150.</i><br /><br />Fluorescence activated cell sorting (FACS) analysis has become a standard tool to analyze cell cycle distributions in populations of cells. These methods require relatively large numbers of cells, and do not provide optimal resolution of the transitions between cell cycle phases. In this report we describe in detail complementary methods that utilize the incorporation of nucleotide analogs combined with microscopic examination. While often more time consuming, these protocols typically require far fewer cells, and allow accurate kinetic assessment of cell cycle progression. We also describe the use of a technique for the synchronization of adherent cells in mitosis by simple mechanical agitation (mitotic shake-off) that eliminates physiological perturbation associated with drug treatments. Analysis of cell cycle phases and progression in cultured mammalian cells Christoph Schorl John Sedivy Methods, Vol. 41, No. 2. (February 2007), pp. 143-150. 2007-07-11T04:56:09-00:00 2007 Methods 41 2 143 150 no-tag