37,663 research outputs found
Abstract 1500: The role of FUBP1 in the hematopoietic system and leukemia
No full textAbstract The transcriptional regulator FUBP1 (Far Upstream Element Binding Protein 1) acts as an oncoprotein in hepatocellular carcinoma (HCC) and is important for hematopoietic stem cell (HSC) self-renewal and erythroid maturation in mice. In this study, we investigated the transcriptional network by which FUBP1 controls hematopoiesis and elucidated the relevance of FUBP1 for human erythropoiesis. Furthermore, we shed light on the role of FUBP1 in leukemia initiating cells. Searching for upstream-regulators of FUBP1, we identified E-boxes as potential TAL1 binding sites in the FUBP1 promoter. Indeed, we demonstrated the regulation of FUBP1 expression by TAL1 in human primary CD34+ donor cells. In chromatin immunoprecipitation (ChIP) experiments, the binding of TAL1 to the FUBP1 promoter increased during erythroid differentiation, correlating with up-regulated FUBP1 and TAL1 expression. Activation of the FUBP1 promoter by TAL1 binding was confirmed in luciferase assays. We observed a reduction in erythroid colony-forming units and glycophorin A positive cells derived from erythroid differentiated human CD34+ cells upon knockdown of FUBP1, supporting the hypothesis that FUBP1 is required for efficient erythropoiesis. In the transduction/transplantation leukemia mouse models for BCR-ABL1+ CML and MLL-AF9+ AML, we observed that Fubp1 knockdown resulted in reduced total cell and progenitor cell numbers. In CML, Fubp1 knockdown cells showed lower cell cycle activity and increased apoptosis. Consistently, CML and AML mice transplanted with Fubp1 knockdown cells survived longer than control mice that received transduced bone marrow expressing wildtype FUBP1 levels. Furthermore, pharmacological treatment of AML mice with the FUBP1 inhibitor irinotecan prolonged their survival significantly as a single drug or in combination with Ara-C. Analysis of FUBP1 expression in bone sections derived from CML and AML patients, and from healthy donors by immunohistochemistry showed no increased FUBP1 expression in leukemic samples, but we noticed a shorter overall survival in those AML patients with strong FUBP1 expression. In CML patients, FUBP1 levels correlate with the disease stage. Thus, elevated expression of FUBP1 might be an indicator for the aggressiveness of leukemia. Our data identify TAL1 as an FUBP1 upstream-regulator and confirm the importance of FUBP1 for HSC self-renewal and erythroid maturation, not only in murine but also in human cells. Furthermore, FUBP1 acts as an oncogenic factor in leukemia. Our findings might provide important evidence for the potential use of FUBP1 in clinical settings, e.g. as a molecular target for the treatment of leukemia patients and as a modulator for the production of red cells. Citation Format: Marlene Steiner, Van T. Hoang, Jasmin Yillah, Katharina Gerlach, Jörn Lausen, Hans-Michael Kvasnicka, Thomas Oellerich, Hanibal Bohnenberger, Daniela Krause, Martin Zörnig. The role of FUBP1 in the hematopoietic system and leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1500
The international consensus classification of myeloid and lymphoid neoplasms
No full textDeveloped by 149 experts in the field, The International Consensus Classification of Myeloid and Lymphoid Neoplasms provides key information for use at the microscope to assist in arriving at a swift and accurate diagnosis. Drs. Daniel Arber, Michael J. Borowitz, James Cook, Laurence de Leval, John Goodlad, Robert Hasserjian, Rebecca L. King, Hans-Michael Kvasnicka, and Attilio Orazi lead a team of authors who focus on diagnostic criteria and the clinical significance of each disease entity
Michael Rodriguez interviews fiction writer Michael Kimball
No full textAuthor Michael Kimball talks about moving away from Michigan to become a successful writer, his education, the fiction reading series he has started in Baltimore, the life-story-on-postcard project, and his book "Dear everybody." Kimball is interviewed by Michigan State University Librarian Michael Rodriguez for the Michigan State University Libraries' Michigan Writers Series
Michael Rodriguez interviews author Paul Clemens
No full textAuthor Paul Clemens talks about his book "Made in Detroit," the genre of memoir, and writing about race. Clemens is interviewed by Michigan State University Librarian Michael Rodriguez for the MSU Libraries' Michigan Writers Series. Held in the MSU Main Library
Paternal Uncertainty and the Economics of Mating, Marriage, and Parental Investment in Children
No full textWe develop a theoretical model of mating behavior and parental investment in children under asymmetry in kin recognition between men and women that provides a microfoundation for the institution of marriage. In the model, men and women derive utility from consumption and reproductive success, which is a function of the number and quality of own offspring. Because of paternal uncertainty, men unlike women may err in investing resources in offspring that is not biologically theirs. As a socially sanctioned commitment device among partners, the institution of marriage reduces this risk by restraining promiscuity in society. Both women and men are shown to benefit from lower levels of paternal uncertainty, as does average child quality because of increased parental investments. As an analytical framework, the model is suitable to study a number of societal, economic, and technological changes in their effects on marriage patterns. A combination of factors is argued to underlie the demise of marriage.Mating, Paternal Uncertainty, Parental Investment, Marriage
Michael Rodriguez interviews author Tom Springer
No full textAuthor Tom Springer is interviewed about his writing career and his newest book "Looking for hickories". Springer talks about his career following after earning an Environmental Journalism degree from Michigan State University. He calls his genre "creative non-fiction" and explains how he weaves his memories into his books about life in rural and wild Michigan. Part of the Michigan State University Libraries' Michigan Writers Series. Springer is interviewed by Librarian Michael Rodriguez
Michael Rodriguez interviews author Gary Gildner
No full textAuthor Gary Gildner explains why he left his tenured teaching position to move to Idaho to became a full-time writer of poetry. Gildner talks about donating his personal papers to Michigan State University Libraries' Special Collections, his writing style and how he approaches writing. Gildner is interviewed by MSU Librarian Michael Rodriguez for the MSU Libraries' Michigan Writer Series. Held at the MSU Main Library
Gold standard of UK degrees is lost in translation
No full textInflated marks, overworked staff and politically compromised courses are the price of exploiting offshore UK registered students, says Michael Day
Michael Rodriguez interviews historian and author Keith Widder
No full textHistorian and author Keith Widder talks about his move to Michigan from Wisconsin, his career as Curator of History for the Mackinac Island State Park Commission, his research interests, his book "Michigan Agricultural College", and his current projects. Widder is interviewed by Michigan State University Librarian Michael Rodriguez for the MSU Libraries' Michigan Writers Series. Held in the MSU Main Library
Uncertain Paternity, Mating Market Failure, and the Institution of Marriage
No full textThis paper provides a first microeconomic foundation for the institution of marriage. Based on a model of reproduction, mating, and parental investment in children, we argue that marriage serves the purpose of attenuating the risk of mating market failure that arises from incomplete information on individual paternity. Raising the costs of mating to individuals, marriage circumscribes female infidelity and mate poaching among men, which reduces average levels of paternal uncertainty in society. A direct gain in male utility, the latter induces men to invest more in their putative offspring, a fact that benefits women because of the public good nature of children. Able to realize Pareto improvements, marriage as an institution is hence explained as the result of a societal consensus on the need to organize and structure mating behavior and reproduction in society for the benefit of paternal certainty and biparental investment in offspring.Marriage, Mating, Paternal Uncertainty, Parental Investment.
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