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The urea cycle disorders (UCDs) are important models for developing gene replacement therapy for liver diseases. Long-term correction of the most common UCD, ornithine transcarbamylase (OTC) deficiency, has yet to be achieved in clinical or preclinical settings. The single human clinical trial using early-generation adenovirus (Ad) failed to show any biochemical correction. In adult OTC-deficient mice, an E1/E2-deleted Ad vector expressing the mouse OTC gene, but not the human, was only transiently therapeutic. By using post-transcriptional overexpression in the context of the less immunogenic helper-dependent adenoviral vector, we achieved metabolic correction of adult OTC-deficient mice for >6 months. Demonstrating this result were normalized orotic aciduria, normal hepatic enzyme activity, and elevated OTC RNA and protein levels in the absence of chronic hepatotoxicity. Overexpressing the human protein may have overcome two potential mechanisms accounting for poor cross-species complementation: a kinetic block at the level of mitochondrial import or a dominant negative effect by the mutant polypeptide. These data represent an important approach for treating human inborn errors of hepatocyte metabolism like the UCDs that require high-level transduction and gene expression for clinical correction. [Copyright &y& Elsevier]

Reports on the examination of nutrient dynamics and soil disturbances since 1979 on paired control and intensively managed watersheds in central Maine. Harvest of mature spruce-fir stand and application of triclopyr to watershed; Application of nitrogen fertilizer to a subset of thinned plots; Increase in soil solution nitrate and cation concentrations by nitrogen fertilization.

An experiment was conducted so examine the impact of simultaneous threats to social- and self-esteem on evaluation apprehension. Subjects were told they would take a potentially ego-threatening test and that only they, only another individual, both they and the other individual, or no one would see their test scores. Prior to the test, evaluation apprehension was assessed. Results showed that potential threats to self- and social-esteem both increased apprehension, but only in the absence of the other type of ego threat. Further, the presence of both sources of threat did not produce greater apprehension titan either threat alone. Also, subjects who scored low versus high on a measure of self-esteem differed in their reactions to social- and self-esteem threats. Results suggest that the effects of conjoint threats to social- and self-esteem are no: cumulative. [ABSTRACT FROM AUTHOR]