University of Iowa

About: University of Iowa is a education organization based out in Iowa City, Iowa, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 49229 authors who have published 109171 publications receiving 5021465 citations. The organization is also known as: UI & The University of Iowa.

CREB-binding protein sequestration by expanded polyglutamine

Abstract: Spinal and bulbar muscular atrophy (SBMA) is one of eight inherited neurodegenerative diseases known to be caused by CAG repeat expansion The expansion results in an expanded polyglutamine tract, which likely confers a novel, toxic function to the affected protein Cell culture and transgenic mouse studies have implicated the nucleus as a site for pathogenesis, suggesting that a critical nuclear factor or process is disrupted by the polyglutamine expansion In this report we present evidence that CREB-binding protein (CBP), a transcriptional co-activator that orchestrates nuclear response to a variety of cell signaling cascades, is incorporated into nuclear inclusions formed by polyglutamine-containing proteins in cultured cells, transgenic mice and tissue from patients with SBMA We also show CBP incorporation into nuclear inclusions formed in a cell culture model of another polyglutamine disease, spinocerebellar ataxia type 3 We present evidence that soluble levels of CBP are reduced in cells expressing expanded polyglutamine despite increased levels of CBP mRNA Finally, we demonstrate that over-expression of CBP rescues cells from polyglutamine-mediated toxicity in neuronal cell culture These data support a CBP-sequestration model of polyglutamine expansion disease

Staphylococcus aureus Biofilms Prevent Macrophage Phagocytosis and Attenuate Inflammation In Vivo

Abstract: Biofilms are complex communities of bacteria encased in a matrix composed primarily of polysaccharides, extracellular DNA, and protein. Staphylococcus aureus can form biofilm infections, which are often debilitating due to their chronicity and recalcitrance to antibiotic therapy. Currently, the immune mechanisms elicited during biofilm growth and their impact on bacterial clearance remain to be defined. We used a mouse model of catheter-associated biofilm infection to assess the functional importance of TLR2 and TLR9 in the host immune response during biofilm formation, because ligands for both receptors are present within the biofilm. Interestingly, neither TLR2 nor TLR9 impacted bacterial density or inflammatory mediator secretion during biofilm growth in vivo, suggesting that S. aureus biofilms circumvent these traditional bacterial recognition pathways. Several potential mechanisms were identified to account for biofilm evasion of innate immunity, including significant reductions in IL-1β, TNF-α, CXCL2, and CCL2 expression during biofilm infection compared with the wound healing response elicited by sterile catheters, limited macrophage invasion into biofilms in vivo, and a skewing of the immune response away from a microbicidal phenotype as evidenced by decreases in inducible NO synthase expression concomitant with robust arginase-1 induction. Coculture studies of macrophages with S. aureus biofilms in vitro revealed that macrophages successful at biofilm invasion displayed limited phagocytosis and gene expression patterns reminiscent of alternatively activated M2 macrophages. Collectively, these findings demonstrate that S. aureus biofilms are capable of attenuating traditional host proinflammatory responses, which may explain why biofilm infections persist in an immunocompetent host.

Who Are We? The Challenges to America's National Identity

Abstract: Who Are We? The Challenges to America's National Identity. By Samuel P. Huntington. New York: Simon and Schuster, 2004. 448p. $27.00.Samuel Huntington suggests in this book that American national identity is threatened by a tidal wave of Latino—primarily Mexican—immigrants who are refusing to assimilate to American “Anglo-Protestant” values, and who are facilitated in this resistance by the erosion of elite support for those very same values. That erosion is a consequence of the “cults of multiculturalism and diversity” (p. 144) that have collectively “denounced the idea of Americanization,” “downgraded the centrality of English,” and “advocated legal recognition of group rights and racial preferences” (p. 142), strong charges indeed.

Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study

Abstract: Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death.