A systems approach to prion disease

Prions cause transmissible neurodegenerative diseases and replicate by conformational conversion of normal benign forms of prion protein (PrPC) to disease-causing PrPSc isoforms. A systems approach to disease postulates that disease arises from perturbation of biological networks in the relevant organ. We tracked global gene expression in the brains of eight distinct mouse strain–prion strain combinations throughout the progression of the disease to capture the effects of prion strain, host genetics, and PrP concentration on disease incubation time. Subtractive analyses exploiting various aspects of prion biology and infection identified a core of 333 differentially expressed genes (DEGs) that appeared central to prion disease. DEGs were mapped into functional pathways and networks reflecting defined neuropathological events and PrPSc replication and accumulation, enabling the identification of novel modules and modules that may be involved in genetic effects on incubation time and in prion strain specificity. Our systems analysis provides a comprehensive basis for developing models for prion replication and disease, and suggests some possible therapeutic approaches

Phase equilibria for iron-rich Fe−Cu−C alloys: 1500 to 950°C

Isothermal sections for the iron rich corner of the Fe-Cu-C system have been constructed at 1500, 1450, 1200, 1172, 1150, 1000, and 950°C. A ternary invariant point exists at 1172°C where an iron rich liquid, a copper rich liquid, austenite, and graphite coexist. The iron rich liquid contains 3.7 wt pct Cu and 4.0 wt pct C. The austenite contains 7.3 pct Cu and 1.6 pct C. The copper rich liquid contains 2.4 pct Fe, and apparently very little carbon. The diagrams are used to explain the phenomena of inverse segregation that occurs during the solidification of iron rich Fe-Cu-C alloys. © 1979 American Society for Metals and the Metallurgical Society of AIME