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Low levels of DNA damage caused by oxidative stress can be repaired, whereas extensive damage usually results in cell death. p53 contributes to both outcomes by stimulating expression of either pro- or antioxidant genes (pages 1306–1313).
Local levels of cAMP regulate the precise opening of the ryanodine receptor complex—which releases calcium at the start of a heartbeat. Loss or inhibition of phosphodiesterase 4D enzymatic activity leads to calcium leak, heart failure and arrhythmia.
Maintenance of the retinal vasculature protects against proliferative retinopathy and blindness. Lipids and free radicals together modulate vascular stability through regulation of antiangiogenic proteins (pages 1339–1345).
Abdominal aortic aneurysms arise from chronic, irreversible destruction of connective tissue. A promising pharmacologic approach not only suppresses development of aneurysms, but also induces regression (pages 1330–1338).
Infants with seizures have few treatment options, because anticonvulsants effective in adults rarely work. A widely used diuretic takes advantage of the unique physiology of the developing brain and could lead to a therapy (pages 1205–1213).
Toll-like receptors act as mediators of injury or repair in the inflamed lung, and the balance depends on the integrity of a component of the extracellular matrix (pages 1173–1179).
In several neurodegenerative disorders, including Parkinson disease, specific neurons are vulnerable to death whereas others are spared. It now appears that the neurotransmitter dopamine may damage parkin, a neuroprotective protein, in susceptible neurons and contribute to their demise (pages 1214–1221).
The extracellular matrix is traditionally regarded as a facilitator of tumor progression, providing an environment in which cells can grow and metastasize. Three new studies take the matrix out of this context and suggest that the microenvironment can not only subsidize, but also initiate, the oncogenic conversion of epithelial cells.
Immunity is partly destroyed by the effects of high-dose chemotherapy associated with hematopoietic stem cell transplantation. A new strategy restores impaired immunity in people and offers clues to improving vaccination against pathogens and tumors (pages 1230–1237).
A new approach to hematopoietic cell transplantation in people seems to lessen the incidence of a serious complication, acute graft-versus-host disease.
