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Full-Text Articles in Medicine and Health Sciences

Fibroblast Growth Factor 2 Endocytosis In Endothelial Cells Proceed Via Syndecan-4-Dependent Activation Of Rac1 And A Cdc42-Dependent Macropinocytic Pathway, Eugene Tkachenko, Esther Lutgens, Radu-Virgil Stan, Michael Simons Feb 2004

Fibroblast Growth Factor 2 Endocytosis In Endothelial Cells Proceed Via Syndecan-4-Dependent Activation Of Rac1 And A Cdc42-Dependent Macropinocytic Pathway, Eugene Tkachenko, Esther Lutgens, Radu-Virgil Stan, Michael Simons

Dartmouth Scholarship

Full activity of fibroblast growth factors (FGFs) requires their internalization in addition to the interaction with cell surface receptors. Recent studies have suggested that the transmembrane proteoglycan syndecan-4 functions as a FGF2 receptor. In this study we investigated the molecular basis of syndecan endocytosis and its role in FGF2 internalization in endothelial cells. We found that syndecan-4 uptake, induced either by treatment with FGF2 or by antibody clustering, requires the integrity of plasma membrane lipid rafts for its initiation, occurs in a non-clathrin-, non-dynamin-dependent manner and involves Rac1, which is activated by syndecan-4 clustering. FGF2 was internalized in a complex …


Trans-Snare Interactions Elicit Ca2+ Efflux From The Yeast Vacuole Lumen, Alexey J. Merz, William T. Wickner Jan 2004

Trans-Snare Interactions Elicit Ca2+ Efflux From The Yeast Vacuole Lumen, Alexey J. Merz, William T. Wickner

Dartmouth Scholarship

Ca2+ transients trigger many SNARE-dependent membrane fusion events. The homotypic fusion of yeast vacuoles occurs after a release of lumenal Ca2+. Here, we show that trans-SNARE interactions promote the release of Ca2+ from the vacuole lumen. Ypt7p-GTP, the Sec1p/Munc18-protein Vps33p, and Rho GTPases, all of which function during docking, are required for Ca2+ release. Inhibitors of SNARE function prevent Ca2+ release. Recombinant Vam7p, a soluble Q-SNARE, stimulates Ca2+ release. Vacuoles lacking either of two complementary SNAREs, Vam3p or Nyv1p, fail to release Ca2+ upon tethering. Mixing these two vacuole populations together allows Vam3p and Nyv1p to interact in trans and …


Effect Of Escherichia Coli And Lactobacillus Rhamnosus On Macrophage Inflammatory Protein 3Α, Tumor Necrosis Factor Alpha, And Transforming Growth Factor Β Release By Polarized Rat Uterine Epithelial Cells In Culture, M. A. Crane-Godreau, C. R. Wira Jan 2004

Effect Of Escherichia Coli And Lactobacillus Rhamnosus On Macrophage Inflammatory Protein 3Α, Tumor Necrosis Factor Alpha, And Transforming Growth Factor Β Release By Polarized Rat Uterine Epithelial Cells In Culture, M. A. Crane-Godreau, C. R. Wira

Dartmouth Scholarship

Entry of bacteria from the vagina into the uterus raises the question of uterine epithelial cell (UEC) signaling in response to the presence of bacteria. Our model system helps to define microbially elicited UEC basolateral cytokine release, important in regulating underlying stromal immune cell protection. UECs from adult rats were grown in cell culture inserts to establish a confluent polarized monolayer as was determined by transepithelial resistance (TER). Polarized epithelial cell cultures were treated apically with live or heat-killed Escherichia coli or Lactobacillus rhamnosus prior to collection of basolateral media after 24 h of incubation. Coculture of polarized UECs with …


Bcma Is Essential For The Survival Of Long-Lived Bone Marrow Plasma Cells, Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George Mantchev, Richard J. Bram, Randolph J. Noelle Jan 2004

Bcma Is Essential For The Survival Of Long-Lived Bone Marrow Plasma Cells, Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George Mantchev, Richard J. Bram, Randolph J. Noelle

Dartmouth Scholarship

Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by inter- leukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this 􏰀-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in …


Slbp Is Associated With Histone Mrna On Polyribosomes As A Component Of The Histone Mrnp, Michael L. Whitfield, Handan Kaygun, Judith A. Erkmann, W. H. Davin Townley-Tilson, Zbig Dominski, William F. Marzluff Jan 2004

Slbp Is Associated With Histone Mrna On Polyribosomes As A Component Of The Histone Mrnp, Michael L. Whitfield, Handan Kaygun, Judith A. Erkmann, W. H. Davin Townley-Tilson, Zbig Dominski, William F. Marzluff

Dartmouth Scholarship

The stem–loop binding protein (SLBP) binds the 3′ end of histone mRNA and is present both in nucleus, and in the cytoplasm on the polyribosomes. SLBP participates in the processing of the histone pre-mRNA and in translation of the mature message. Histone mRNAs are rapidly degraded when cells are treated with inhibitors of DNA replication and are stabilized by inhibitors of translation, resulting in an increase in histone mRNA levels. Here, we show that SLBP is a component of the histone messenger ribonucleoprotein particle (mRNP). Histone mRNA from polyribosomes is immunoprecipitated with anti-SLBP. Most of the SLBP in cycloheximide-treated cells …


Inactivation Of A Bacterial Virulence Pheromone By Phagocyte-Derived Oxidants: New Role For The Nadph Oxidase In Host Defense, Jacob M. Rothfork, Graham S. Timmins, Michael N. Harris, Xian Chen, Aldons J. Lusis, Michael Otto, Ambrose L. Cheung, Hattie D. Gresham Jan 2004

Inactivation Of A Bacterial Virulence Pheromone By Phagocyte-Derived Oxidants: New Role For The Nadph Oxidase In Host Defense, Jacob M. Rothfork, Graham S. Timmins, Michael N. Harris, Xian Chen, Aldons J. Lusis, Michael Otto, Ambrose L. Cheung, Hattie D. Gresham

Dartmouth Scholarship

Quorum sensing triggers virulence factor expression in medically important bacterial pathogens in response to a density-dependent increase in one or more autoinducing pheromones. Here, we show that phagocyte-derived oxidants target these autoinducers for inactivation as an innate defense mechanism of the host. In a skin infection model, expression of phagocyte NADPH oxidase, myeloperoxidase, or inducible nitric oxide synthase was critical for defense against a quorum-sensing pathogen, Staphylococcus aureus, but not for defense against a quorum sensing-deficient mutant. A virulence-inducing peptide of S. aureus was inactivated in vitro and in vivo by reactive oxygen and nitrogen intermediates, including HOCl and ONOO(-). …


Cd40-Associated Traf 6 Signaling Is Required For Disease Induction In A Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Cory L. Ahonen, W. James Cook, William R. Green Jan 2004

Cd40-Associated Traf 6 Signaling Is Required For Disease Induction In A Retrovirus-Induced Murine Immunodeficiency, Kathy A. Green, Cory L. Ahonen, W. James Cook, William R. Green

Dartmouth Scholarship

LP-BM5 retrovirus-infected C57BL/6 mice develop splenomegaly, lymphadenopathy, hypergammaglobulinemia, and immunodeficiency; thus, this disease has been named mouse AIDS. In this syndrome, CD154/CD40 interactions are required for but do not mediate disease by upregulation of CD80 or CD86. We report here that there is nonetheless a necessity for CD40 signaling competence, specifically an intact tumor necrosis factor receptor-associated factor 6 (TRAF 6) binding site.


The Nuclear Pore Complex And The Dead Box Protein Rat8p/Dbp5p Have Nonessential Features Which Appear To Facilitate Mrna Export Following Heat Shock, Christiane Rollenhagen, Christine A. Hodge, Charles N. Cole Jan 2004

The Nuclear Pore Complex And The Dead Box Protein Rat8p/Dbp5p Have Nonessential Features Which Appear To Facilitate Mrna Export Following Heat Shock, Christiane Rollenhagen, Christine A. Hodge, Charles N. Cole

Dartmouth Scholarship

Nuclear pore complexes (NPCs) play an essential role in RNA export. Nucleoporins required for mRNA export in Saccharomyces cerevisiae are found in the Nup84p and Nup82p subcomplexes of the NPC. The Nup82p subcomplex contains Nup82p, Rat7p/Nup159p, Nsp1p, Gle1p/Rss1p, and Rip1p/Nup42p and is found only on the cytoplasmic face of NPCs. Both Rat7p and Gle1p contain binding sites for Rat8p/Dbp5p, an essential DEAD box protein and putative RNA helicase. Rip1p interacts directly with Gle1p and is the only protein known to be essential for mRNA export after heat shock but not under normal growth conditions. We report that in cells lacking …