Papers by christopher leo
Urban Affairs Review, 1998
The author argues that the apparent ineffectuality of efforts to control urban sprawl is in some ... more The author argues that the apparent ineffectuality of efforts to control urban sprawl is in some part a result of a failure to distinguish between growth controls, which have a well-earned reputation as a thinly veiled form of NIMBYism and regional growth management (RGM), which involves the attempt to set out rules for development that are designed to preserve the livability, viability, and attractiveness of an urban area as a whole. This study surveys emerging political forces favoring RGM and notes signs that a new constellation of forces is emerging. It assesses the significance of this shift.
Book Reviews/Comptes rendus
Canadian Journal of African Studies / Revue canadienne des études africaines, 1992
The Global Economy and the Local State
Power in the Global Era, 2000
Local politics has long been subject to influences originating in the global economy, but it is o... more Local politics has long been subject to influences originating in the global economy, but it is only lately that students of urban political economy have begun to appropriate a language and a set of concepts intended to comprehend that reality.1 Much work remains to be done. In this article, I look at urban politics in North America and Europe, with special attention to the politics of planning and development, ask how globalization is changing the political landscape, and enquire into the local political response to the challenge of globalization.
Funding or dividing Aboriginal communities? A Winnipeg case study
Built upon a centuries-old, deeply troubled neo-colonial relationship, the federal government'... more Built upon a centuries-old, deeply troubled neo-colonial relationship, the federal government's aboriginal policy in Winnipeg addresses a wide variety of very real community needs. At the same time, it is marked by disingenuous reporting of funding, a paternalistic attitude toward the aboriginal leadership, and – most seriously of all – methods of implementation that could hardly have been better calculated to exacerbate already sharp divisions within the aboriginal community. The article offers suggestions for a better approach.
City Politics in an Era of Globalization
Reconstructing Urban Regime Theory: Regulating Urban Politics in a Global Economy
Molecular and Cellular Biology, 2000
PML fuses with retinoic acid receptor α (RARα) in the t(15;17) translocation that causes acute pr... more PML fuses with retinoic acid receptor α (RARα) in the t(15;17) translocation that causes acute promyelocytic leukemia (APL). In addition to localizing diffusely throughout the nucleoplasm, PML mainly resides in discrete nuclear structures known as PML oncogenic domains (PODs), which are disrupted in APL and spinocellular ataxia cells. We isolated the Fas-binding protein Daxx as a PML-interacting protein in a yeast two-hybrid screen. Biochemical and immunofluorescence analyses reveal that Daxx is a nuclear protein that interacts and colocalizes with PML in the PODs. Reporter gene assay shows that Daxx drastically represses basal transcription, likely by recruiting histone deacetylases. PML, but not its oncogenic fusion PML-RARα, inhibits the repressor function of Daxx. In addition, SUMO-1 modification of PML is required for sequestration of Daxx to the PODs and for efficient inhibition of Daxx-mediated transcriptional repression. Consistently, Daxx is found at condensed chromatin in ...
Is the Federal Government Dividing the Aboriginal Community? Can It Stop? A Winnipeg Case Study
Page 1. IS THE FEDERAL GOVERNMENT DIVIDING THE ABORIGINAL COMMUNITY? CAN IT STOP? A WINNIPEG CASE... more Page 1. IS THE FEDERAL GOVERNMENT DIVIDING THE ABORIGINAL COMMUNITY? CAN IT STOP? A WINNIPEG CASE STUDY by Christopher Leo University of Winnipeg with Martine August University of Toronto and Matthew D. Rogers University of British Columbia ...
The Regulation and Function of Nuclear Receptor Corepressor SMRT in Human Breast Cancer Cells
T + f* AD Award Number: DAMD17-98-1-8206 TITLE: The Regulation and Function of Nuclear Receptor C... more T + f* AD Award Number: DAMD17-98-1-8206 TITLE: The Regulation and Function of Nuclear Receptor Corepressor SMRT in Human Breast Cancer Cells PRINCIPAL INVESTIGATOR:Christopher Leo J. Don Chen, Ph.D. ... 6. AUTHOR(S) Christopher Leo J. Don Chen, Ph.D. ...
Nucleic Acids Research, 2004
Analysis of genomic DNA derived from cells and fresh or ®xed tissues often requires whole genome ... more Analysis of genomic DNA derived from cells and fresh or ®xed tissues often requires whole genome ampli®cation prior to microarray screening. Technical hurdles to this process are the introduction of ampli®cation bias and/or the inhibitory effects of formalin ®xation on DNA ampli®cation. Here we demonstrate a balanced-PCR procedure that allows unbiased ampli®cation of genomic DNA from fresh or modestly degraded paraf®n-embedded DNA samples. Following digestion and ligation of a target and a control genome with distinct linkers, the two are mixed and ampli®ed in a single PCR, thereby avoiding biases associated with PCR saturation and impurities. We demonstrate genome-wide retention of allelic differences following balanced-PCR ampli®cation of DNA from breast cancer and normal human cells and genomic pro®ling by array-CGH (cDNA arrays, 100 kb resolution) and by realtime PCR (single gene resolution). Comparison of balanced-PCR with multiple displacement ampli®cation (MDA) demonstrates equivalent performance between the two when intact genomic DNA is used. When DNA from paraf®n-embedded samples is used, balanced PCR overcomes problems associated with modest DNA degradation and produces unbiased ampli®cation whereas MDA does not. Balanced-PCR allows ampli®cation and recovery of modestly degraded genomic DNA for subsequent retrospective analysis of human tumors with known outcomes.
Molecular Endocrinology, 1997
SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear recept... more SMRT (silencing mediator of retinoic acid and thyroid hormone receptor) and N-CoR (nuclear receptor corepressor) are two related transcriptional corepressors that contain separable domains capable of interacting with unliganded nuclear receptors and repressing basal transcription. To decipher the mechanisms of receptor interaction and transcriptional repression by SMRT/N-CoR, we have characterized protein-protein interacting surfaces between SMRT and nuclear receptors and defined transcriptional repression domains of both SMRT and N-CoR. Deletional analysis reveals two individual nuclear receptor domains necessary for stable association with SMRT and a C-terminal helix essential for corepressor dissociation. Coordinately, two SMRT domains are found to interact independently with the receptors. Functional analysis reveals that SMRT contains two distinct repression domains, and the corresponding regions in N-CoR also repress basal transcription. Both repression domains in SMRT and N-C...
Journal of Biological Chemistry, 2006
Maintenance of the cells of the vessel wall in a quiescent state is an important aspect of normal... more Maintenance of the cells of the vessel wall in a quiescent state is an important aspect of normal vascular physiology. Transcriptional repressors are widely believed to regulate this process, yet the exact factors involved and the mechanism of repression are not known. Here, we report that the POU domain transcription factor Oct-1 represses the expression of E-selectin and vascular cell adhesion molecule (VCAM-1), two cytokine-inducible, NF-B-dependent endothelial-leukocyte adhesion molecules that participate in the leukocyte recruitment phase of the inflammatory response. Co-transfection and microinjection studies demonstrate that Oct-1 blocks tumor necrosis factor ␣-stimulated E-selectin and VCAM-1 expression. Gene expression arrays indicate that control of tumor necrosis factor ␣-induced, NF-B-dependent gene expression by Oct-1 is promoter-specific. A DNA-binding mutant of Oct-1 represses NF-B-dependent reporter gene expression. Biochemically, Oct-1 interacts with p65, suggesting that Oct-1 is involved in the regulation of NF-B transactivation function. NF-B-dependent gene expression is more pronounced in Oct-1-deficient than in wild-type murine embryonic fibroblasts, and reintroduction of human Oct-1 abolishes these differences. Finally, the cytokine interleukin-6 induces Oct-1 gene expression, providing a biologically relevant means by which NF-B-dependent gene expression can be selectively reverted by Oct-1 to quiescent levels. At sites of vascular dysfunction, multiple signaling pathways are activated that can modulate gene expression. Rapid and transient induction of a select set of transcription factors, such as nuclear factor-B (NF-B), 6 is followed by the expression of
Genome Research, 2004
Despite recent advances in linear whole genome amplification of intact DNA/RNA, amplification of ... more Despite recent advances in linear whole genome amplification of intact DNA/RNA, amplification of degraded nucleic acids in an unbiased fashion remains a serious challenge for genetic diagnosis. We describe a new whole genome amplification procedure, RCA–RCA (Restriction and Circularization-Aided Rolling Circle Amplification), which retains the allelic differences among degraded amplified genomes while achieving almost complete genome coverage. RCA–RCA utilizes restriction digestion and whole genome circularization to generate genomic sequences amenable to rolling circle amplification. When intact genomic DNA is used, RCA–RCA retains gene-amplification differences (twofold or higher) between complex genomes on a genome-wide scale providing highly improved concordance with unamplified material as compared with other amplification methodologies including multiple displacement amplification. Using RCA–RCA, formalin-fixed samples of modest or substantial DNA degradation were successfully...
Gene, 2000
Nuclear hormone receptors are ligand-dependent transcription factors that regulate genes critical... more Nuclear hormone receptors are ligand-dependent transcription factors that regulate genes critical to such biological processes as development, reproduction, and homeostasis. Interestingly, these receptors can function as molecular switches, alternating between states of transcriptional repression and activation, depending on the absence or presence of cognate hormone, respectively. In the absence of hormone, several nuclear receptors actively repress transcription of target genes via interactions with the nuclear receptor corepressors SMRT and NCoR. Upon binding of hormone, these corepressors dissociate away from the DNA-bound receptor, which subsequently recruits a nuclear receptor coactivator (NCoA) complex. Prominent among these coactivators is the SRC (steroid receptor coactivator) family, which consists of SRC-1, TIF2/GRIP1, and RAC3/ACTR/pCIP/AIB-1. These cofactors interact with nuclear receptors in a ligand-dependent manner and enhance transcriptional activation by the receptor via histone acetylation/methylation and recruitment of additional cofactors such as CBP/p300. This review focuses on the mechanism of action of SRC coactivators in terms of interactions with receptors and activation of transcription. Specifically, the roles of the highly conserved LXXLL motifs in mediating SRC function will be detailed. Additionally, potential diversity among SRC family members, as well as several recently cloned SRC-associated cofactors, will be discussed.
Cancer Research, 2004
Cancer represents the phenotypic end point of multiple genetic lesions that endow cells with a fu... more Cancer represents the phenotypic end point of multiple genetic lesions that endow cells with a full range of biological properties required for tumorigenesis. Among the hallmark features of the cancer genome are recurrent regional gains and losses that, upon detailed characterization, have provided highly productive discovery paths for new oncogenes and tumor suppressor genes. In this study, we describe the use of an oligonucleotide-based microarray platform and development of requisite assay conditions and bioinformatic mining tools that permits high-resolution genome-wide array-comparative genome hybridization profiling of human and mouse tumors. Using a commercially available 60-mer oligonucleotide microarray, we demonstrate that this platform provides sufficient sensitivity to detect single-copy difference in gene dosage of full complexity genomic DNA while offering high resolution. The commercial availability of the microarrays and associated reagents, along with the technical ...
Canadian Journal of Political Science, 2009
The ideas of economists and political philosophers, both when they are right and when they are wr... more The ideas of economists and political philosophers, both when they are right and when they are wrong, are more powerful than is commonly understood. Indeed, the world is ruled by little else. Practical men, who believe themselves to be quite exempt from any intellectual influences, are usually the slaves of some defunct economist.
The Politics of the City: A Canadian Perspective Timothy L. Thomas, ed. Toronto: ITP Nelson, 1997, pp. xvi, 230
Canadian Journal of Political Science, 1997
gone wrong elsewhere. Freeman is generally on the mark as regards the economic troubles of nuclea... more gone wrong elsewhere. Freeman is generally on the mark as regards the economic troubles of nuclear power and the corresponding evolution of Hydro. He notes, for example, the 1982 collapse in the face of high interest rates of Hydro's nationalistic nuclear electric energy strategy and a simultaneous organizational shift from "social purpose" (managed growth) to "business logic" (166). He senses as well that such a shift leads towards a logic of privatization and, probably as well, nonnuclear options. We will, one suspects, soon see this part of the drama played out in the headlines of the coming years.
Canadian Journal of Political Science/Revue canadienne de science politique, 2006
The Canadian federal-provincial system of government is recognized as one of the most unique in t... more The Canadian federal-provincial system of government is recognized as one of the most unique in the world. While the founding fathers originally envisaged a relatively centralized system of government, reflecting their desire for a powerful national authority, political realities soon deemed that a more decentralized form of government would prevail. Influenced by both domestic and international factors, the Canadian federal system evolved throughout the 20 th century. Provincial governments increasingly asserted their rights to attain the jurisdictional powers necessary to achieve their goals, and demanded to be placed on a near-equal footing with the federal government. 1 The process by which this unfolded was long, grueling and conflict-ridden, but was essential if Canada were to function in the face of intense regionalism. 2 The process reached in culmination in the Constitution Act of 1982, which enshrined the two-tier federalprovincial system.
Metropolitan growth and municipal boundaries: Problems and proposed solutions
International Journal of Canadian Studies, 2001
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Multi-level Governance: Getting the Job Done and Respecting Community DifferenceThree Winnipeg Cases
Canadian Political Science Review, 2007
Multi-level governance is seen by different commentators as addressing a varied array of concerns... more Multi-level governance is seen by different commentators as addressing a varied array of concerns. Some see it as a means of fulfilling the norms of the new public management, and thereby of freeing the administration of government programs from the constraints ...
Immigration and Settlement in Saint John, New Brunswick: Community Perspectives on a Federal-Provincial Agreement
Winnipeg: University of Winnipeg, 2006
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Papers by christopher leo