136 research outputs found

    NF-κB Antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to Suppress Caspase-8 Activation

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    Tumor necrosis factor α (TNF-α) binding to the TNF receptor (TNFR) potentially initiates apoptosis and activates the transcription factor nuclear factor kappa B (NF-κB), which suppresses apoptosis by an unknown mechanism. The activation of NF-κB was found to block the activation of caspase-8. TRAF1 (TNFR-associated factor 1), TRAF2, and the inhibitor-of-apoptosis (IAP) proteins c-IAP1 and c-IAP2 were identified as gene targets of NF-κB transcriptional activity. In cells in which NF-κB was inactive, all of these proteins were required to fully suppress TNF-induced apoptosis, whereas c-IAP1 and c-IAP2 were sufficient to suppress etoposide-induced apoptosis. Thus, NF-κB activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-α–mediated apoptosis and that function more distally to suppress genotoxic agent–mediated apoptosis

    Identification of the Schistosoma mansoni TNF-Alpha Receptor Gene and the Effect of Human TNF-Alpha on the Parasite Gene Expression Profile

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    Schistosoma mansoni is the major causative agent of schistosomiasis in the Americas. This parasite takes advantage of host signaling molecules such as cytokines and hormones to complete its development inside the host. Tumor necrosis factor-alpha (TNF-α) is one of the most important host cytokines involved in the inflammatory response. When cercariae, the infective stage, penetrates the human skin the release of TNF-α is started. In this work the authors describe the complete sequence of a possible TNF-α receptor in S. mansoni and detect that the receptor is most highly expressed in cercariae among all life cycle stages. Aiming to mimic the situation at the site of skin penetration, cercariae were mechanically transformed in vitro into schistosomula and exposed to human TNF-α. Exposure of early-developing schistosomula to the human hormone caused a large-scale change in the expression of parasite genes. Exposure of adult worms to human TNF-α caused gene expression changes as well, and the set of parasite altered genes in the adult parasite was different from that of schistosomula. This work increases the number of known signaling pathways of the parasite, and opens new perspectives into understanding the molecular components of TNF-α response as well as into possibly interfering with parasite–host interaction

    PREPARATION OF (Th,U)Csub2sub 2 FUEL PARTICLES FOR THE HTGR

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    A process that was developed for the preparation of particles of thorium- uranium dicarbide is described. Granulated particles composed of powdered UO/sub 2/, ThO/sub 2/, and carbon were suspended in a bed of graphite flour and heated to convert the oxides to dicarbides. The particles were then melted to densify and spheroidize them, the graphite flour keeping them separated so that they would not flow together. (auth

    Magnetic and Structual Studies on Mn-In System

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    Boron Carbide-Graphite Nuclear Control-Rod Material: Preparation, Thermal Stability, and Irradiation Evaluation

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    Boron carbide-graphite nuclear control-rod materials containing up to 45 wt% B were prepared by hot-pressing techniques. The densities of these compacts decreased with increasing B content. Compact strengths, however, were noticeably increased with B content of 20 wt%, suggesting that the B acts as a sintering aid. Thermal stability was evaluated by annealing compacts under a variety of temperature and atmospheric conditions. The upper limit of the ioss of 13 was 5% to 10%~ in 200 hr at 2000 deg C--considerably less than would be predicted from the Langmuir evaporation equation. Diffusion of B atoms through the pores of the graphite, rather than evaporation from the surface, was found to be the rate- controlling step in the loss of B. Compacts containing 20, 30, and 40 wt% B were irradiated at 350 and 700 deg C to 1.0 and 2 4 x 10/sup 21/ nvt(fast). Physical integrity of the compacts was good after irradiation. Slight increases in tensile strength were noted in several instances. (auth

    Bacterial synthesis of a novel human leukocyte interferon.

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    A novel human leukocyte interferon cDNA clone (LeIF B) was identified in a cDNA library prepared using polyadenylated mRNA of a myeloblastoid cell line. The nucleotide sequence of LeIF B differs significantly from other published leukocyte interferon cDNA sequences. An expression plasmid was constructed which directs the synthesis in E. coli of 8 x 10(7) interferon units per liter of culture. LeIF B exhibits markedly different specificities from another bacterially synthesized human leukocyte interferon, LeIF A
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