Evidence of a conserved functional role for DNA methylation in termites.

Many organisms are capable of developing distinct phenotypes from the same genotype. This developmental plasticity is particularly prevalent in insects, which can produce alternate adaptive forms in response to distinct environmental cues. The ability to develop divergent phenotypes from the same genotype often relies on epigenetic information, which affects gene function and is transmitted through cell divisions. One of the most important epigenetic marks, DNA methylation, has been lost in several insect lineages, yet its taxonomic distribution and functional conservation remain uninvestigated in many taxa. In the present study, we demonstrate that the signature of high levels of DNA methylation exists in the expressed genes of two termites, Reticulitermes flavipes and Coptotermes formosanus. Further, we show that DNA methylation is preferentially targeted to genes with ubiquitous expression among morphs. Functional associations of DNA methylation are also similar to those observed in other invertebrate taxa with functional DNA methylation systems. Finally, we demonstrate an association between DNA methylation and the long-term evolutionary conservation of genes. Overall, our findings strongly suggest DNA methylation is present at particularly high levels in termites and may play similar roles to those found in other insects.

DNA methylation in insects: on the brink of the epigenomic era.

DNA methylation plays an important role in gene regulation in animals. However, the evolution and function of DNA methylation has only recently emerged as the subject of widespread study in insects. In this review we profile the known distribution of DNA methylation systems across insect taxa and synthesize functional inferences from studies of DNA methylation in insects and vertebrates. Unlike vertebrate genomes, which tend to be globally methylated, DNA methylation is primarily targeted to genes in insects. Nevertheless, mounting evidence suggests that a specialized role exists for genic methylation in the regulation of transcription, and possibly mRNA splicing, in both insects and mammals. Investigations in several insect taxa further reveal that DNA methylation is preferentially targeted to ubiquitously expressed genes and may play a key role in the regulation of phenotypic plasticity. We suggest that insects are particularly amenable to advancing our understanding of the biological functions of DNA methylation, because insects are evolutionarily diverse, display several lineage-specific losses of DNA methylation and possess tractable patterns of DNA methylation in moderately sized genomes.

Primary biliary cirrhosis: MR imaging findings and description of MR imaging periportal halo sign.

OBJECTIVE: This study reviews the prevalence of MR imaging abnormalities seen in 21 consecutive patients with primary biliary cirrhosis before transplantation and describes a new MR imaging sign in these patients: the MR imaging periportal halo sign. CONCLUSION: Abdominal adenopathy was present in 62% of the patient population, and none of the patients with adenopathy had a known malignancy. Findings associated with end-stage cirrhosis and portal hypertension were seen and included ascites (62%), splenomegaly (71%), portosystemic collaterals (57%), portal vein thrombosis (5%), and hepatocellular carcinoma (5%). The MR imaging periportal halo sign was seen in 43% of patients with primary biliary cirrhosis, but none of the patients in a sex- and age-matched cohort of 21 patients with cirrhosis not caused by primary biliary cirrhosis had the finding. Statistical analysis of these results produced a t score of 3.97 and a p value of less than 0.001, suggesting that this new MR imaging sign is highly specific for the diagnosis of primary biliary cirrhosis.

Diagnostic evaluation of hepatocellular carcinoma in a cirrhotic liver.

Hepatocellular carcinoma (HCC) is one of the world's most common cancers. It is closely associated with cirrhosis, especially that due to viral hepatitis. The incidences of viral hepatitis and HCC are rising steadily in the United States. When symptomatic, HCC is usually unresectable and associated with a median survival of less than 6 months. Nodular lesions of undetermined malignant potential are often found in cirrhotic, explanted livers. There appears to be a continuum of increasing malignant potential from regenerating nodules to dysplastic nodules and to HCC. Pathologic differentiation of high-grade dysplastic nodules from HCC is often difficult. Early diagnosis offers the best potential for curative intervention. Screening of high-risk patient populations using serum alpha-fetoprotein and ultrasound has been attempted but is hindered by low sensitivity and specificity. The multinodularity and vascular flow anomalies of the cirrhotic liver complicate imaging. However, recent advances in magnetic resonance imaging technology allow for more accurate examination of the liver. We review the current status of hepatic imaging techniques and the results of screening a high-risk population for HCC.

An analysis of the relationship between the cellular distribution and the rate of turnover for the separate classes of unoccupied, noncovalently occupied, and covalently occupied insulin receptor.

To further investigate insulin's role in regulating the turnover of insulin receptor during down-regulation in 3T3-L1 adipocytes, the relationship between the cellular distribution and turnover of unoccupied, noncovalently occupied, and covalently occupied receptor was examined. At steady-state 12% of the unoccupied receptors and 46% of covalently occupied receptors are intracellular. The apparent first-order rate constant (Kapp) for turnover of the total pool of covalently occupied receptors (0.16 h-1) is 3.8-fold higher than that for unoccupied receptors (0.042 h-1). When unlabeled insulin is added, identical values for both Kapp (0.10 h-1) and distribution (26% internal) are measured for noncovalently and covalently occupied receptors. The rate constant (Kdeg), describing the relative sensitivity of internalized receptor to degradation, is identical (0.36-0.41 h-1) for unoccupied, noncovalently occupied, and permanently occupied pools of internal receptor. Mechanisms for down-regulation postulating: (a) an occupancy-dependent alteration in the conformation of internal receptor increasing receptor sensitivity to internal proteases, (b) a preferential sorting of internal occupied receptor to degradative pathways, or (c) induction of intracellular proteases by insulin, would all reflect a substantial change in Kdeg for occupied receptor and thus are unlikely mechanisms by which insulin increases the rate of receptor turnover. The turnover of insulin receptor in 3T3-L1 adipocytes is regulated primarily by its intracellular concentration and not by the state of occupancy of internalized receptor.