News & Views in 2007

In a new role for an ion transporter, Na⁺-K⁺-Cl⁻ cotransporter-1 may regulate the lung endothelial and epithelial barriers and consequently modulate the host response to pneumonia and sepsis.

Necrosis induces inflammation, but how necrotic cells signal to immune cells was poorly understood. New work by Chen et al. shows that IL-1α acts as a mediator, translating a signal from the necrotic cells to induce the recruitment of immune cells to the site of injury (pages 851–856).

Mutations in the phosphoinositide metabolism gene FIG4 disrupt the endosomal pathway, leading to neurodegeneration and a newly identified variant of Charcot-Marie-Tooth disorder.

In psoriasis, expression of the α₁β₁ integrin is necessary for T cells to enter the epidermis to cause inflammation and psoriatic lesions (pages 836–842).

The factors that regulate airway goblet cell metaplasia and mucus secretion are essential to understanding how airway obstruction occurs in asthma. In this issue, Xiang et al. demonstrate the existence of an airway epithelial, extraneuronal GABAergic signaling system that promotes mucus overproduction during allergic airway inflammation (pages 862–867).

In response to intense stress, neuropeptide Y facilitates all of the processes that result in adipose tissue growth, but only when mice are fed a palatable high-fat diet (pages 803–811).

Introducing four genes into mouse skin fibroblasts reprograms these cells into embryonic stem cells. If similar techniques work in human cells, patient-specific stem cells for tissue engineering and cell-based therapies may be closer to reality.

Aberrant activation of the protein phosphatase calcineurin is found in various cancer types. Inhibition of calcineurin leads to a rapid clearance of leukemic cells and significantly improves animal survival in two mouse models of acute T lymphoblastic leukemia.

Hydrogen gas debuts as a selective antioxidant with explosive potential as cytoprotective therapy for ischemia-reperfusion injury and stroke.

Non-small-cell lung cancers with activating mutations in the epidermal growth factor receptor develop resistance to tyrosine kinase inhibitors by recruiting the MET receptor kinase to activate HER3 and the PI3K-Akt cell survival pathway.

In a mouse model of cerebral malaria, free heme molecules can induce inflammation and permeabilization of the blood brain barrier, leading to death. The enzyme heme oxygenase-1 or its product carbon monoxide can decrease free heme levels, offering a new therapeutic approach to this deadly complication.

Retinaldehyde, an intermediate metabolite between vitamin A and retinoic acid, is present at biologically active concentrations in fat tissue, where it antagonizes PPAR-γ activity, inhibiting adipogenesis and improving insulin sensitivity.

Imaging of inflammation in atherosclerotic lesions may identify plaques vulnerable to rupture, and lead to better assessment of individuals at risk for acute coronary events such as myocardial infarction (pages 636–641).

The genetic basis of autism is beginning to come to light. De novo mutations in gene copy number may have a big role.

A single molecule, osteopontin, seems to both amplify and quell the immune response in asthma—depending on the stage of the asthmatic reaction. The findings hint that, if given at the right stage, osteopontin might have value as a therapy (pages 570–578).

A key regulator of the neuromuscular junction, the transcriptional co-activator PGC-1α, is a potential target for Duchenne muscular dystrophy therapy.