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Digital technology is changing our politics. The World Wide Web is already a powerful influence on the public's access to government documents, the tactics and content of political campaigns, the behavior of voters, the efforts of activists to circulate their messages, and the ways in which topics enter the public discourse. The essays collected here capture the richness of current discourse about democracy and cyberspace. Some contributors offer front-line perspectives on the impact of emerging technologies on politics, journalism, and civic experience. What happens, for example, when we increase access to information or expand the arena of free speech? Other contributors place our shifting understanding of citizenship in historical context, suggesting that notions of cyber-democracy and online community must grow out of older models of civic life. Still others consider the global flow of information and test our American conceptions of cyber-democracy against developments in other parts of the world. How, for example, do new media operate in Castro's Cuba, in post-apartheid South Africa, and in the context of multicultural debates on the Pacific Rim? For some contributors, the new technologies endanger our political culture; for others, they promise civic renewal.

AbstractInherited disorders of mitochondrial oxidative phosphorylation are the most common group of inborn errors of metabolism and cause a wide range of clinical presentations. Mitochondrial DNA encodes 13 protein subunits required for oxidative phosphorylation plus 22 transfer RNAs and two ribosomal RNAs, and mutations in most of these genes cause human disease. Nuclear genes encode most of the protein subunits and all other proteins required for mitochondrial biogenesis and mitochondrial DNA replication and expression. Mutations in 64 nuclear genes and 34 mitochondrial genes are now known to cause mitochondrial disease and many novel mitochondrial disease genes await discovery. The genetic complexity of oxidative phosphorylation means that maternal, autosomal recessive, autosomal dominant and X-linked modes of inheritance can occur, along with de novo mutations. This complexity presents a challenge in planning efficient molecular genetic diagnosis of patients with suspected mitochondrial disease. In some situations, clinical phenotype can be strongly predictive of the underlying genotype. However, more often this is not the case and it is usually helpful, particularly with pediatric patients, to determine whether the activity of one or more of the individual oxidative phosphorylation enzymes is deficient before proceeding with mutation analysis. In this review we will summarize the genetic bases of mitochondrial disease and discuss some approaches to integrate information from clinical presentation, laboratory findings, family history, and imaging to guide molecular investigation.

Fumarase deficiency is a rare autosomal recessive inborn error of metabolism of the Krebs Tricarboxylic Acid cycle. A heavy neurological disease burden is imparted by fumarase deficiency, commonly manifesting as microcephaly, dystonia, global developmental delay, seizures, and lethality in the infantile period. Heterozygous carriers also carry an increased risk of developing hereditary leiomyomatosis and renal cell carcinoma. We describe a non-consanguineous family in whom a dichorionic diamniotic twin pregnancy resulted in twin boys with fumarase deficiency proven at the biochemical, enzymatic, and molecular levels. Their clinical phenotype included hepatic involvement. A novel mutation in the fumarate hydratase gene was identified in this family.