p75NTR , a nerve growth factor co-receptor that has been implicated in apoptosis of neurons, is structurally related to Fas and the receptors for tumor necrosis factor-␣ that display ligand independent assembly into trimers. Using embryonic day 17 fetal rat cortical neurons and p75 NTR -expressing NIH-3T3 cells, we now show that p75 NTR exists as a trimer as well as a monomer. Furthermore, we have reported and others have confirmed that amyloid  binds p75 NTR , and that this binding leads to apoptotic cell death. We now report that amyloid  binds to trimers of p75 NTR as well as to p75 NTR monomers but not to the p140 trkA , the nerve growth factor co-receptor that mediates neuronal survival. Furthermore, amyloid  activates p75 NTR , strongly inducing the transcription of c-Jun mRNA and stimulating the stress-activated c-Jun NH 2 -terminal kinase, as measured by phosphorylation of its substrate (glutathione S-transferase-c-Jun-(1-79)). Our data suggest that p75 NTR may be present as a preformed trimer that binds amyloid  to induce receptor activation, and support the hypothesis that p75 NTR activation by amyloid  is causally related to Alzheimer's disease.
Vascular endothelial growth factor (VEGF) is a potent keratinocyte-derived angiogenic factor. Prior reports suggest that following UV irradiation VEGF in keratinocytes is induced primarily by tumor necrosis factor (TNF)- alpha, a cytokine synthesized and secreted by keratinocytes after UV irradiation. We investigated whether blocking TNF-alpha binding to its receptors would inhibit UV-induced VEGF expression and secretion in the keratinocyte-derived line SCC-12F. Irradiation with physiologic UV doses (30 mJ/cm2) substantially induced VEGF mRNA in this cell line, as expected, and mRNA induction was followed by increased VEGF in medium conditioned by UV-irradiated cells. Also as expected, TNF-alpha induced VEGF expression and secretion in a dose-dependent manner. Addition of a hexapeptide (Ac-KWIIVW-NH2), known to block TNF-alpha binding to its receptors, abrogated this TNF-alpha effect on VEGF mRNA induction. However, addition of the peptide to cells immediately after UV irradiation did not substantially affect VEGF mRNA induction or secretion into the medium. Our results suggest that VEGF induction after UV irradiation is mediated by multiple mechanisms and that blocking a single pathway does not affect the response.
This study was conducted to evaluate the anthelmintic effectiveness of Albizia anthelmintica, as a first step in investigating the hypothesis that livestock self-medicate. In July 2006, an observational study was conducted with 56 young female lambs, to validate A. anthelmintica efficacy. Faecal egg per gram for Coccidia, Strongyle-type, Monezia, Strongyloides and Dicrocoelia eggs were counted and analysed. Results indicate that A. anthelmintica is effective in controlling infection with a variety of internal parasites in lambs, Monezia was the most sensitive. Furthermore, treatment of Strongyle-type worms requires a biweekly dose of A. anthelmintica as an effective deworming protocol.
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