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2006

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Medicine and Health Sciences

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Articles 1 - 11 of 11

Full-Text Articles in Cell Biology

Brca1 Foci In Normal S-Phase Nuclei Are Linked To Interphase Centromeres And Replication Of Pericentric Heterochromatin, Gayle Jeannette Pageau, Jeanne B. Lawrence Dec 2006

Brca1 Foci In Normal S-Phase Nuclei Are Linked To Interphase Centromeres And Replication Of Pericentric Heterochromatin, Gayle Jeannette Pageau, Jeanne B. Lawrence

Open Access Articles

Breast cancer-associated protein 1 (BRCA1) forms foci at sites of induced DNA damage, but any significance of these normal S-phase foci is unknown. BRCA1 distribution does not simply mirror or overlap that of replicating DNA; however, BRCA1 foci frequently abut sites of BrdU incorporation, mostly at mid-to-late S phase. Although BRCA1 does not overlap XIST RNA across the inactive X chromosome, BRCA1 foci position overwhelmingly in heterochromatic regions, particularly the nucleolar periphery where many centromeres reside. In humans and mice, including early embryonic cells, BRCA1 commonly associates with interphase centromere-kinetochore complexes, including pericentric heterochromatin. Proliferating cell nuclear antigen or BrdU ...


Functional Interaction Of The Retinoblastoma And Ini1/Snf5 Tumor Suppressors In Cell Growth And Pituitary Tumorigenesis, Cynthia J. Guidi, Rajini R. Mudhasani, Kathleen Hoover, Andrew Koff, Irwin Leav, Anthony N. Imbalzano, Stephen N. Jones Aug 2006

Functional Interaction Of The Retinoblastoma And Ini1/Snf5 Tumor Suppressors In Cell Growth And Pituitary Tumorigenesis, Cynthia J. Guidi, Rajini R. Mudhasani, Kathleen Hoover, Andrew Koff, Irwin Leav, Anthony N. Imbalzano, Stephen N. Jones

Open Access Articles

The Ini1 subunit of the SWI/SNF chromatin remodeling complex suppresses formation of malignant rhabdoid tumors in humans and mice. Transduction of Ini1 into Ini1-deficient tumor-derived cell lines has indicated that Ini1 arrests cell growth, controls chromosomal ploidy, and suppresses tumorigenesis by regulating components of the retinoblastoma (Rb) signaling pathway. Furthermore, conditional inactivation of Ini1 in mouse fibroblasts alters the expression of various Rb-E2F-regulated genes, indicating that endogenous Ini1 levels may control Rb signaling in cells. We have reported previously that loss of one allele of Ini1 in mouse fibroblasts results only in a 15% to 20% reduction in total ...


Supervillin Modulation Of Focal Adhesions Involving Trip6/Zrp-1, Norio Takizawa, Tara C. Smith, Thomas Nebl, Jessica Lynn Crowley, Stephen J. Palmieri, Lawrence M. Lifshitz, Anka G. Ehrhardt, Laura M. Hoffman, Mary C. Beckerle, Elizabeth J. Luna Aug 2006

Supervillin Modulation Of Focal Adhesions Involving Trip6/Zrp-1, Norio Takizawa, Tara C. Smith, Thomas Nebl, Jessica Lynn Crowley, Stephen J. Palmieri, Lawrence M. Lifshitz, Anka G. Ehrhardt, Laura M. Hoffman, Mary C. Beckerle, Elizabeth J. Luna

Women’s Health Research Faculty Publications

Cell-substrate contacts, called focal adhesions (FAs), are dynamic in rapidly moving cells. We show that supervillin (SV)--a peripheral membrane protein that binds myosin II and F-actin in such cells--negatively regulates stress fibers, FAs, and cell-substrate adhesion. The major FA regulatory sequence within SV (SV342-571) binds to the LIM domains of two proteins in the zyxin family, thyroid receptor-interacting protein 6 (TRIP6) and lipoma-preferred partner (LPP), but not to zyxin itself. SV and TRIP6 colocalize within large FAs, where TRIP6 may help recruit SV. RNAi-mediated decreases in either protein increase cell adhesion to fibronectin. TRIP6 partially rescues SV effects on ...


The Study Of Nitric Oxide Synthase Expression, Function, And Regulation In The Renal Vasculature During Postnatal Renal Development, Brian Blake Ratliff Apr 2006

The Study Of Nitric Oxide Synthase Expression, Function, And Regulation In The Renal Vasculature During Postnatal Renal Development, Brian Blake Ratliff

Theses and Dissertations in Biomedical Sciences

The newborn kidney is vulnerable to vasomotor acute renal failure (ARF) from adverse perinatal events or complications of prematurity. Nitric oxide (NO) vasodilation is vitally protective in this type of ARF, but its relationship with other vasoactive factors, such as angiotensin II (AII) has not been examined. In the immature kidney, nitric oxide synthase (NOS) isoforms, specifically eNOS and nNOS, are developmentally regulated, but their specific role and regulation are unknown.

The enhanced vasodilatory role of NO in the immature kidney was hypothesized to be attributed to regulatory, expressional, and functional differences in eNOS and nNOS isoforms from the adult ...


Understanding Il-12 Responsiveness During Leishmania Amazonensis Infection , Amanda Ellen Ramer Jan 2006

Understanding Il-12 Responsiveness During Leishmania Amazonensis Infection , Amanda Ellen Ramer

Retrospective Theses and Dissertations

Cutaneous leishmaniasis is a vector-borne disease caused by intracellular protozoan parasites of the genus Leishmania. C3H mice challenged with L. major develop a polarized Th1 response and subsequently heal, whereas L. amazonensis challenge leads to chronic lesions with high parasite loads. This work demonstrates that infection with L. amazonensis creates a population of antigen-responsive, CD44hi CD4+ T cells that proliferate and produce IL-2 but do not polarize to an effector phenotype and exhibit limited IFN-gamma production in response to IL-12. CD44 hi CD4+ T cells from L. amazonensis-infected mice fail to accumulate in culture as compared to cells from L ...


Directed Growth And Selective Differentiation Of Neural Progenitor Cells Using A Synergistic Combination Of Topographical And Soluble Cues , Jennifer Behr Recknor Jan 2006

Directed Growth And Selective Differentiation Of Neural Progenitor Cells Using A Synergistic Combination Of Topographical And Soluble Cues , Jennifer Behr Recknor

Retrospective Theses and Dissertations

The purpose of this study is to develop strategies to facilitate nerve regeneration using a synergistic combination of guidance cues. We are investigating the cellular mechanisms of development using adult rat hippocampal progenitor cells (AHPCs) and have demonstrated that manipulating a combination of physical, chemical and biological cues can lead to oriented astrocyte and neural progenitor cell outgrowth and can influence progenitor cell differentiation. To provide physical guidance, micropatterned polystyrene (PS) substrates were fabricated and chemically modified with laminin. Astrocytes or AHPCs cultured on these substrates align along the grooves of the patterned surface extending highly elongated processes. To further ...


Comparative Study Of Immunocytochemical Patterns Of Somatotrophs, Mammotrophs, And Mammosomatotrophs In The Porcine Anterior Pituitary , Jin-Sook Lee Jan 2006

Comparative Study Of Immunocytochemical Patterns Of Somatotrophs, Mammotrophs, And Mammosomatotrophs In The Porcine Anterior Pituitary , Jin-Sook Lee

Retrospective Theses and Dissertations

The anterior pituitary gland is a dynamic and complex endocrine gland that synthesizes and secretes trophic hormones from distinct endocrine cells including mammotrophs (prolactin cells or lactotrophs) and somatotrophs (growth hormone cells) to play essential roles in the maintenance of homeostasis, metabolism, reproduction, growth, and lactation. Recently, the existence of a novel anterior pituitary cell type, the mammosomatotroph which contained both growth hormone (GH) and prolactin (PRL) was proposed to function as a transitional cell or progenitor cell between somatotrophs and mammotrophs under various physiological conditions. The present study investigated the spatial distribution patterns of somatotrophs, mammotrophs, and mammosomatotrophs by ...


Never Let Me Clone? Countering An Ethical Argument Against The Reproductive Cloning Of Humans, Yvette Pearson Jan 2006

Never Let Me Clone? Countering An Ethical Argument Against The Reproductive Cloning Of Humans, Yvette Pearson

Philosophy Faculty Publications

In the March 2006 issue of EMBO reports, Christof Tannert, a bioethicist at the Max Delbrück Research Centre in Berlin, Germany, presented a moral argument against human reproductive cloning on the basis of Immanuel Kant’s categorical imperative (Tannert, 2006). In this article, I address some problems with Tannert’s views and show that our concerns about this prospective procedure should prompt us to scrutinize carefully the conventional procreative practices and attitudes. Indeed, if we set aside objections that are grounded in genetic determinism, many of the offensive features of human cloning are identical to problems with procreation by more ...


Linking Ligand-Induced Alterations In Androgen Receptor Structure To Differential Gene Expression: A First Step In The Rational Design Of Selective Androgen Receptor Modulators, Dmitri Kazmin, Tatiana Prytkova, C. Edgar Cook, Russell Wolfinger, Tzu-Ming Chu, David Beratan, J. D. Norris, Ching-Yi Chang, Donald P. Mcdonnell Jan 2006

Linking Ligand-Induced Alterations In Androgen Receptor Structure To Differential Gene Expression: A First Step In The Rational Design Of Selective Androgen Receptor Modulators, Dmitri Kazmin, Tatiana Prytkova, C. Edgar Cook, Russell Wolfinger, Tzu-Ming Chu, David Beratan, J. D. Norris, Ching-Yi Chang, Donald P. Mcdonnell

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We have previously identified a family of novel androgen receptor (AR) ligands that, upon binding, enable AR to adopt structures distinct from that observed in the presence of canonical agonists. In this report, we describe the use of these compounds to establish a relationship between AR structure and biological activity with a view to defining a rational approach with which to identify useful selective AR modulators. To this end, we used combinatorial peptide phage display coupled with molecular dynamic structure analysis to identify the surfaces on AR that are exposed specifically in the presence of selected AR ligands. Subsequently, we ...


Endothelial Cell Cortactin Phosphorylation By Src Contributes To Polymorphonuclear Leukocyte Transmigration In Vitro, L. Yang, Jennifer R. Kowalski, X. Zhan, S. M. Thomas, F. W. Luscinskas Jan 2006

Endothelial Cell Cortactin Phosphorylation By Src Contributes To Polymorphonuclear Leukocyte Transmigration In Vitro, L. Yang, Jennifer R. Kowalski, X. Zhan, S. M. Thomas, F. W. Luscinskas

Scholarship and Professional Work - LAS

The underlying mechanisms that regulate leukocyte transendothelial migration through the vascular endothelium remain unclear. Cortactin is a substrate of Src tyrosine kinases and a regulator of cytoskeletal dynamics. Previous studies demonstrated a role for Src phosphorylation of cortactin in clustering of E-selectin and intercellular cell adhesion molecule-1 around adherent leukocytes. In the current study, we used an in vitro flow model to investigate the role of Src-induced cortactin phosphorylation in endothelium during polymorphonuclear leukocyte (PMN) transmigration through human umbilical vein endothelium (HUVEC) monolayers preactivated with tumor necrosis factor-{alpha}. Inhibition of Src in HUVEC using Src kinase inhibitors PP2 and ...


Methods For The Study Of Signaling Molecules In Membrane Lipid Rafts And Caveolae, Rennolds S. Ostrom, Paul A. Insel Jan 2006

Methods For The Study Of Signaling Molecules In Membrane Lipid Rafts And Caveolae, Rennolds S. Ostrom, Paul A. Insel

Pharmacy Faculty Articles and Research

Lipid rafts and caveolae are cholesterol- and sphingolipid-rich microdomains of the plasma membrane that concentrate components of certain signal transduction pathways. Interest in and exploration of these microdomains has grown in recent years, especially after the discovery of the biochemical marker of caveolae, caveolin, and the recognition that caveolin interacts with many different signaling molecules via its scaffolding domain. There are three major types of caveolins (1, 2, and 3), with some selectivity in their expression in different tissues. Results assessing lipid raft/caveolae co-localization of molecules in signal transduction pathways have provided support for the idea that signaling components ...