Cosmological constant in SUGRA models and the multiple point principle

The tiny order of magnitude of the cosmological constant is sought to be explained in a model involving the following ingredients: supersymmetry breaking in N=1 supergravity and the multiple point principle. We demonstrate the viability of this scenario in the minimal SUGRA model.Comment: 18 pages, 2 figures, Talk given at Nuclear Physics Department of the Russian Academy of Sciences (RAS) Conference on Physics of Fundamental Interactions, Moscow, Russia, 2-6 Dec 2002; to appear in Phys.Atom.Nuc

Immunotoxicity of silver nanoparticles in an intravenous 28-day repeated-dose toxicity study in rats.

BACKGROUND Nanosilver is used in a variety of medical and consumer products because of its antibacterial activity. This wide application results in an increased human exposure. Knowledge on the systemic toxicity of nanosilver is, however, relatively scarce. In a previous study, the systemic toxicity of 20 nm silver nanoparticles (Ag-NP) was studied in a 28-day repeated-dose toxicity study in rats. Ag-NP were intravenously administered with a maximum dose of 6 mg/kg body weight (bw)/day. Several immune parameters were affected: reduced thymus weight, increased spleen weight and spleen cell number, a strongly reduced NK cell activity, and reduced IFN-γ production were observed. METHODS Prompted by these affected immune parameters, we wished to assess exposure effects on the functional immune system. Therefore, in the present study the T-cell dependent antibody response (TDAR) to keyhole limpet hemocyanin (KLH) was measured in a similar 28-day intravenous repeated-dose toxicity study. In addition, a range of immunological parameters was measured. Data obtained using the benchmark dose (BMD) approach were analyzed by fitting dose-response models to the parameters measured. RESULTS A reduction in KLH-specific IgG was seen, with a lowest 5% lower confidence bound of the BMD (BMDL) of 0.40 mg/kg bw/day. This suggests that Ag-NP induce suppression of the functional immune system. Other parameters sensitive to Ag-NP exposure were in line with our previous study: a reduced thymus weight with a BMDL of 0.76 mg/kg bw/day, and an increased spleen weight, spleen cell number, and spleen cell subsets, with BMDLs between 0.36 and 1.11 mg/kg bw/day. Because the effects on the spleen are not reflected by increased KLH-specific IgG, they, however, do not suggest immune stimulation. CONCLUSIONS Intravenous Ag-NP administration in a 28-day repeated-dose toxicity study induces suppression of the functional immune system. This finding underscores the importance to study the TDAR to evaluate immunotoxicity and not to rely solely on measuring immune cell subsets

Comparative gene expression profiling in two congenic mouse strains following <it>Bordetella pertussis </it>infection

<p>Abstract</p> <p>Background</p> <p>Susceptibility to <it>Bordetella pertussis </it>infection varies widely. These differences can partly be explained by genetic host factors. HcB-28 mice are more resistant to <it>B. pertussis </it>infection than C3H mice, which could partially be ascribed to the <it>B</it>. <it>pertussis susceptibility locus-1 </it>(<it>Bps1</it>) on chromosome 12. The presence of C57BL/10 genome on this locus instead of C3H genome resulted in a decreased number of bacteria in the lung. To further elucidate the role of host genetic factors, in particular in the <it>Bps1 </it>locus, in <it>B. pertussis </it>infection, and to identify candidate genes within in this region, we compared expression profiles in the lungs of the C3H and HcB-28 mouse strains following <it>B. pertussis </it>inoculation. Twelve and a half percent of the genomes of these mice are from a different genetic background.</p> <p>Results</p> <p>Upon <it>B. pertussis </it>inoculation 2,353 genes were differentially expressed in the lungs of both mouse strains. Two hundred and six genes were differentially expressed between the two mouse strains, but, remarkably, none of these were up- or down-regulated upon <it>B. pertussis </it>infection. Of these 206 genes, 17 were located in the <it>Bps1 </it>region. Eight of these genes, which showed a strong difference in gene expression between the two mouse strains, map to the immunoglobulin heavy chain complex (<it>Igh</it>).</p> <p>Conclusion</p> <p>Gene expression changes upon <it>B. pertussis </it>infection are highly identical between the two mouse strains despite the differences in the course of <it>B. pertussis </it>infection. Because the genes that were differentially regulated between the mouse strains only showed differences in expression before infection, it appears likely that such intrinsic differences in gene regulation are involved in determining differences in susceptibility to <it>B. pertussis </it>infection. Alternatively, such genetic differences in susceptibility may be explained by genes that are not differentially regulated between these two mouse strains. Genes in the <it>Igh </it>complex, among which <it>Igh-1a/b</it>, are likely candidates to explain differences in susceptibility to <it>B. pertussis</it>. Thus, by microarray analysis we significantly reduced the number of candidate susceptibility genes within the <it>Bps1 </it>locus. Further work should establish the role of the <it>Igh </it>complex in <it>B. pertussis </it>infection.</p