News & Views in 2010

Blood coagulation protects from microbial infections. A recent study now shows that neutrophils fine tune the procoagulant response to invading pathogens (pages 887–896). Neutrophils degrade an inhibitor of coagulation, locally 'trapping' bacteria in small blood vessels. But they also increase blood clots in large vessels in the absence of infection, which may be relevant for the treatment of thrombosis.

The angiogenic switch, which leads to the activation of endothelial cell proliferation and the growth of new blood vessels, is a crucial step in tumorigenesis. A study now shows that this process is linked to a microRNA in endothelial cells (909–914). Blocking microRNAs may offer new avenues for antiangiogenesis therapy to treat cancer.

Findings in mice and people suggest that glycosphingolipids have a role in the formation of large fluid-filled cysts in polycystic kidney disease. An inhibitor of glycosphingolipid synthesis may provide a potential therapy for this disorder, which often progresses to kidney failure (pages 788–792).

Chromosomal translocations can promote cancers by eliciting the expression of fusion genes with oncogenic activity. The identification of translocations affecting RAF genes in prostate and gastric cancers and melanoma provides compelling evidence for the key role of RAF signaling in a subset of these cancers and suggests possible new avenues for personalized cancer therapy (pages 793–798).

Ephrin-B2 is required for the formation of blood and lymphatic vessels, but the mechanism has been enigmatic. Two independent studies show that ephrin-B2 controls the internalization and signaling of two types of vascular endothelial growth factor (VEGF) receptors—thereby regulating VEGF-induced angiogenesis in normal and pathological conditions.

The stress response protein Rtp801 mediates damage to the lung in response to smoke. This finding might lead to new ways to treat chronic obstructive pulmonary disease and emphysema (pages 767–773).

Pregnancy increases the demand for insulin by various tissues in the body, a condition that can lead to gestational diabetes. To shield against this condition, insulin-producing beta cells proliferate in a process now shown to involve the local production of serotonin in response to lactogenic hormones (pages 804–808).

Basophils have recently been identified as antigen-presenting cells that are required for optimal antibody responses. New findings now show that activation of these cells can amplify autoimmune responses in systemic lupus erythematosus (SLE) (pages 701–707).

Activation of Toll-like receptor (TLR) signaling by microbes in the intestine promotes tumor growth in genetically susceptible mice. Inactivation of extracellular signal–regulated kinase (ERK), a molecule downstream of TLR signaling, may offer a route to preventing colorectal cancer (pages 665–670).

Cytokines have a fundamental role in orchestrating innate immune responses to bacterial infections. Interleukin-33 (IL-33) is now shown to protect from sepsis by promoting neutrophil influx into the focus of infection (pages 708–712).

There is no cure for osteoarthritis—the most common disease of the joints. By piecing together the molecular events that drive the progression of this debilitating disease, recent studies published in Nature Medicine put hypoxia-inducible factor-2α (HIF-2α) in the driver's seat, opening up new avenues for early detection and treatment (pages 678–686 and 687–693).

Mammalian genomes harbor regulatory elements from ancient retroviral infections. These retroviral remnants are normally silenced by DNA methylation—but this can change. Reactivation of one such element triggers the expression of a nearby oncogene during the development of Hodgkin's lymphoma (571–579).

Approximately 5% of people that are hospitalized for any reason develop acute kidney failure, which, in some cases, progresses to a chronic condition resulting in fibrosis of the kidney and permanent changes in the organ's function. Two new studies suggest that cell cycle arrest of epithelial cells and epigenetic modifications have key roles in the switch to chronic disease (pages 535–543 and 544–550).

T lymphocytes engineered to produce T cell receptors specific for tumor antigens lead to an antitumor immune response. New findings draw attention to a potentially deadly problem with this strategy. The transgenic T cell receptors can shuffle components with native receptors to produce hybrid molecules with specificity against self antigens (pages 565–570).

Pain caused by chronic inflammation is a serious health problem. But the currently available analgesic drugs cause major side effects when taken long term. A new study points to a class of molecules, resolvins, which not only provide analgesia and are well tolerated but may also reduce inflammation (pages 592–597).

Many parasites vary their surface molecules to avoid the host's immune response, thereby perpetuating long-term infections. Disrupting this process in the intestinal parasite Giardia lamblia now provides a useful tool for vaccination (pages 551–557).

Activation of Toll-like receptors (TLRs) via a nuclear protein released from dying cells, high-mobility group box-1 (HMGB1) protein, leads to chronic epilepsy in rat models and in human epileptic tissue. Blocking this inflammatory pathway may constitute a new antiepileptic treatment strategy (pages 413–419).

The HIV drug raltegravir, which blocks viral integration into the genome, results in a transient increase in episomes, circularized HIV DNA. The findings suggest that persistent HIV replication occurs in people on antiretroviral therapy. Measuring episomes may also offer a new method to study viral persistence and latency and to gauge the effectiveness of antiviral regimens (pages 460–465).