Begell House Inc.
Critical Reviews™ in Eukaryotic Gene Expression
CRE
1045-4403
16
1
2006
An Integrated Biological Approach to Nuclear Receptor Signaling in Physiological Control and Disease
1-22
10.1615/CritRevEukarGeneExpr.v16.i1.10
Carsten
Carlberg
Institut fur Physiologische Chemie I, Heinrich-Heine-Universitat Dusseldorf, D-40001 Dusseldorf, Germany
Thomas W.
Dunlop
Department of Biochemistry, University of Kuopio, FIN-70211 Kuopio, Finland
The nuclear receptors (NRs)—vitamin D receptor (VDR); peroxisome proliferator-activated receptor (PPAR) α, δ, γ; and pregnane X receptor (PXR)—act as sensors for various molecules encountered by the body on a daily basis. The effects of these ligands can be understood by the fact that numerous genes involved in the cellular processes, such as general homeostasis, growth, and defense against microbes, are under the control of these five NRs. The target gene and protein expression patterns of VDR, PPARs, and PXR; the resulting changes in metabolite levels; and their physiological consequences create a network that can be monitored by high-throughput methods and analyzed by multimodal approaches, such as systems biology. We suggest that the fine regulation of this NR network is specific to each human individual and depends, in part, on the constellation of regulatory small nucleotide polymorphisms (SNPs) in his or her genome. When regulatory SNPs affect NRs response elements, lifetime exposure to food components will have different accumulative consequences on the expression of the respective NR target genes. These differences will influence the individual's susceptibility to aging-related diseases, such as type 2 diabetes, atherosclerosis, cancer, and osteoporosis. Furthermore, it is anticipated that systems biology methods will also help to identify the most critical genes, proteins, or metabolites in the NR network that will serve as biomarkers for the early detection of these diseases.
Silencing or Knocking Out Eukaryotic Gene Expression by Oligodeoxynucleotide Decoys
23-30
10.1615/CritRevEukarGeneExpr.v16.i1.20
Kenneth R.
Cutroneo
Department of Biochemistry, University of Vermont, College of Medicine, 89 Beaumont Avenue, Burlington, VT 05405
H. Paul
Ehrlich
Division of Plastic Surgery, Penn State University, College of Medicine, 500 University Avenue, Hershey, PA 17033
The elucidation of molecular and signaling pathways in eukaryotic cells is often achieved by targeting regulatory element(s) found in the promoter or the enhancer region of eukaryotic gene(s) using a double-stranded (ds) oligodeoxynucleotide (ODN) containing a specific cis-element. Our laboratory is focusing on dsODN decoys containing the TGF-β element as a novel nonsteroidal antifibrotic for achieving normal wound healing. In the model systems discussed, there is either a specific gene possessing a specific cis-element or a cluster of genes with one gene containing the consensus cis-element. The rest of the genes in the cluster contain the cis-elements homologous to this consensus element, which allows for dsODN decoy regulation of a gene cluster at one time.
RUNX Expression and Function in Human B Cells
31-44
10.1615/CritRevEukarGeneExpr.v16.i1.30
Hannah J.
Whiteman
Department of Virology, Imperial College Faculty of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, UK
Paul J.
Farrell
Department of Virology, Imperial College Faculty of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, UK
RUNX1 and RUNX3 are expressed at many stages of B-cell differentiation, suggesting that they play a role in the development and functions of this lineage. Transgenic mice lacking expression of RUNX1 or the RUNX protein-binding partner, CBFβ, have defective B-cell development, with differentiation blocked at an early stage. Specific knockout of RUNX1 in adult hematopoietic cells also caused a decrease in the number of mature B cells, supporting a role for RUNX1 in both developmental and adult hematopoiesis. Furthermore, RUNX proteins have been shown to regulate several B-cell-specific genes and play an important role in TGF-β-induced immunoglobulin class switching to IgA. The importance of RUNX1 in B-cell development is additionally demonstrated by its dysregulation in the t(12;21) translocation, which is the most frequent translocation found in acute lymphocytic leukemia. Epstein Barr virus immortalized human B lymphoblastoid cell lines express RUNX3, and cross-regulation of RUNX1 by RUNX3 occurs in these cells. Knockdown of RUNX3 in these cells induces RUNX1 expression and inhibits cell proliferation, directly showing that RUNX proteins can regulate B-cell growth.
Biocompatible Nanometal Particle Fluorescence Enhancers
45-60
10.1615/CritRevEukarGeneExpr.v16.i1.40
Kyung A.
Kang
Department of Chemical Engineering, University of Louisville, Louisville, KY 40292
Bin
Hong
Department of Chemical Engineering, University of Louisville, Louisville, KY 40292
Fluorometry has been used for more than a century to enhance the understanding of phenomena in molecular biology. With recent advances in light detection techniques, it is even more actively used in research now. The effectiveness of fluorometry highly depends on the intensity of the fluorescence from the target molecules in contrast to the background. Instrumentation for amplifying fluorescence signals may not selectively enhance signals only from the target. Therefore, a method to retrieve more fluorescence emission from a fluorophore is beneficial. Nanometal particles have high-density surface plasmon polariton fields, and when a fluorophore is placed within these fields, the electrons involved in the fluorescence emission may be altered in their energy states. The level of alteration depends upon the metal type, size of the particle, quantum yield of a fluorophore, and, most importantly, the distance between the nanoparticle and the fluorophore. Some organic solvents are also found to enhance fluorescence, possibly by the dipole-dipole coupling between the fluorophore and the solvent, resulting in an increase in the energy gap between the excited and the ground states. In this article, study results of the application of nanometal particles and biocompatible solvents for increasing the sensitivity/resolution in fluorophore-mediated biosensing/bioimaging are reviewed.
PET-Based Biological Imaging for Radiation Therapy Treatment Planning
61-102
10.1615/CritRevEukarGeneExpr.v16.i1.50
Pat
Zanzonico
Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, NY
Biologically conformal radiation therapy (BCRT), a convergence of intensity-modulated radiation therapy (IMRT) and positron emission tomography (PET)-based functional imaging, incorporates patient-specific, image-derived biological information. This approach may potentially lead to a paradigm shift in radiation therapy—spatially varying dose prescriptions, or dose sculpting, for individualized and dosimetrically optimized treatment. This article reviews the current status of the technical, biological, and clinical aspects of PET-guided radiation therapy. It remains unclear, however, whether PET is currently capable of delineating the true extent of viable tumor with sufficient accuracy and precision to reliably guide therapy on a routine basis.