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Cell-surface glycans are known to alter as Barrett's esophagus progresses to adenocarcinoma, leading to specific changes in lectin binding patterns. Bird-Lieberman and her colleagues have exploited this knowledge to develop a new endoscopic approach that uses fluorescent-labeled lectins to visualize pre-cancerous, high-grade dysplastic lesions in Barrett's esophagus that cannot be detected by conventional endoscopy. The method uses commonly available endoscopic equipment, provides a wide field of view and is shown here in ex vivo esophageal tissue.
The authors identify a new tumor suppressor role for Smurf2 that is linked to its regulation of histone modifications through RNF20. In the absence of Smurf2 in mice, and potentially also when its nuclear function is compromised in human tumors, higher levels of histone ubiquitination lead to a relaxation of chromatin structure, and alterations in DNA repair result in compromised genomic instability and increased tumorigenesis in aging mice. The findings suggest that loss of Smurf2 function may underlie tumor initiation by reshaping the epigenetic landscape of cells.
Mutations in the type I ryanodine receptor (RYR1), a calcium channel, leads to stimulus-induced pathological muscle contractions, including malignant hyperthermia. Currently there are no pharmacological agents to protect against this condition, but Susan Hamilton and her colleagues have now identified AICAR as one possible candidate compound. To date, AICAR has been thought to be an AMPK activator, but her group shows that in a mouse model of malignant hyperthermia it does not target this kinase, but rather RYR1, to prevent improper calcium leakage and pathology.
The Niemann-Pick C1–like 1 cholesterol uptake receptor is an entry factor for the hepatitis C virus, according to this report. Ezetimibe, a drug that targets this receptor and is approved for use in humans, inhibits infection by the hepatitis C virus in a mouse model, highlighting the therapeutic potential of this discovery.
The search for compounds to treat neurodegenerative disorders is especially pressing given the rapidly growing elderly human population and has led to the consideration of sirtuin proteins as potential therapeutic candidates. Two studies now report that modulating the expression of the sirtuin Sirt1 has therapeutic benefit in Huntington's disease mouse models and identify putative downstream targets of Sirt1 involved in improved disease outcomes (pages 159–165 and 153–158).
The beneficial cytoprotective effects of heme oxygenase-1 (HO-1) in malaria infection are counterpoised by higher susceptibility to nontyphoidal Salmonella (NTS) bacteremia. A new study in mice co-infected with malaria and Salmonella provides a mechanism for the long-recognized association between malaria and NTS infection in African children.
A new study in mice shows that platelet-derived growth factor-B (PDGF-B) boosts tumor growth by exerting a double function after induction of erythropoietin (EPO) expression from stromal components—a proangiogeneic response in the endothelium and hematopoietic stimulation (pages 100–110).