Enzymatic denitrification of 2-nitropropane in uninduced mouse liver microsomes

Hepatic microsomes from 5 strains of untreated mice were tested for the ability to enzymatically cleave the nitro group from 2-nitropropane (2NP). All strains showed significant NADPH-dependent nitrite release at pH 7.6 and pH 8.8. Statistical differences in nitrite-releasing activity between strains were found between BALB and PL/J and ATH strains at pH 7.6. At pH 8.8, BIO.M differed from CD-1 and BALB. These results are in contrast to a report of little or no denitrification activity in uninduced rats and suggest that the 2NP microsomal metabolism may be of greater importance than previously thought.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25607/1/0000154.pd

Gene-Disease Network Analysis Reveals Functional Modules in Mendelian, Complex and Environmental Diseases

Scientists have been trying to understand the molecular mechanisms of diseases to design preventive and therapeutic strategies for a long time. For some diseases, it has become evident that it is not enough to obtain a catalogue of the disease-related genes but to uncover how disruptions of molecular networks in the cell give rise to disease phenotypes. Moreover, with the unprecedented wealth of information available, even obtaining such catalogue is extremely difficult. We developed a comprehensive gene-disease association database by integrating associations from several sources that cover different biomedical aspects of diseases. In particular, we focus on the current knowledge of human genetic diseases including mendelian, complex and environmental diseases. To assess the concept of modularity of human diseases, we performed a systematic study of the emergent properties of human gene-disease networks by means of network topology and functional annotation analysis. The results indicate a highly shared genetic origin of human diseases and show that for most diseases, including mendelian, complex and environmental diseases, functional modules exist. Moreover, a core set of biological pathways is found to be associated with most human diseases. We obtained similar results when studying clusters of diseases, suggesting that related diseases might arise due to dysfunction of common biological processes in the cell. For the first time, we include mendelian, complex and environmental diseases in an integrated gene-disease association database and show that the concept of modularity applies for all of them. We furthermore provide a functional analysis of disease-related modules providing important new biological insights, which might not be discovered when considering each of the gene-disease association repositories independently. Hence, we present a suitable framework for the study of how genetic and environmental factors, such as drugs, contribute to diseases. The gene-disease networks used in this study and part of the analysis are available at http://ibi.imim.es/DisGeNET/DisGeNETweb.html#Download