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Three reactions diversify antibody genes in human somatic cells of the B lineage: VDJ recombination, somatic hypermutation and class-switch recombination. The discovery of activation-induced cytidine deaminase (AID) has led to the elucidation of a unified molecular mechanism for initiation of the last two reactions and suggests why B cells undergoing these reactions are prone to cancer-associated DNA damage.
A study in mice traces the path of West Nile virus into the brain. Viral replication in peripheral tissues triggers a Toll-like receptor inflammatory response that alters the blood-brain barrier (pages 1366–1373).
Drug discovery is either an exact business that is based on detailed knowledge of target structure or it is a fishing expedition that uncovers new drugs through screening of random compounds for their biological effect on target function. Isolation of a new p53 activator with anticancer properties strengthens the reputation of this second approach (pages 1321–1328).
Gallstones develop in response to an imbalance of lipids in bile, the digestive fluid produced in the liver. A compound that restores the balance prevents gallstone formation in mouse models (pages 1352–1358).
The US Food and Drug Administration has approved only one therapy for ischemic stroke, recombinant tissue plasminogen activator (tPA), which can increase blood flow to damaged brain tissue—but it can also have severe side effects and must be administered shortly after stroke. Experiments combining the drug with activated protein C (APC) may provide a solution (pages 1379–1383).
The human genome is peppered with genes for small microRNAs, whose functions are only beginning to come to light. One such microRNA is now implicated in the secretion of insulin from pancreatic beta cells.
Once activated, some T cells home to distinct sites in the body, such as the intestine and inflamed skin. Research in mice shows that dendritic cells in the gut produce a derivative of vitamin A, retinoic acid, that gives T cells directions.
The acetylcholine receptor modulates interactions between the nervous system and the immune system. An acetylcholine receptor agonist, nicotine, is now harnessed to dampen inflammation and reduce mortality in a mouse model of sepsis (pages 1216–1221).
It is common knowledge that high salt intake can contribute to high blood pressure, but the reasons have not been clear. Fresh insight emerges from mouse studies showing how smooth muscle cells in blood vessels respond to changes in salt balance (pages 1193–1199).