Articles in 2009

In June 2006, Warwick Anderson became chief executive of Australia’s National Health and Medical Research Council (NHMRC) as the institution gained new status as a fully independent agency. He talked to Simon Grose about his first three years in the job and the NHMRC’s accelerated evolution.

The deposition of excess scar tissue that occurs in lung fibrosis is known to be mediated by transforming growth factor-β (TGF-β). Prostaglandin F_2α and the F prostanoid (FP) receptor are now identified as mediators that act independently of TGF-β (pages 1426–1430).

A molecular pathway known for regulating cholesterol and lipid metabolism is now implicated in stroke (pages 1399–1406). The pathway is bumped up by N-methyl-D-aspartate glutamate receptors (NMDARs), which are hyperactivated in stroke and other conditions.

Innovation in translational research has often emerged from the biotechnology industry. In a climate in which it is increasingly hard to found a successful company, direct technology transfer from academia to the pharmaceutical industry poses an additional threat to small biotechs.

Some of the key papers published in 2009

This year witnessed both surprising successes and unexpected failures in basic and clinical drug development. There were also mixed results for some newly tested drugs, which will probably prompt a careful reassessment of their therapeutic value. Our drug watch compilation summarizes the most talked about therapies of the year.

Excessive stimulation of glutamate receptors results in excitotoxicity and has a role in a variety of neurodegenerative disorders, including Huntington's disease. By blocking pathological extrasynaptic activity but preserving normal synaptic function, the N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine—at the proper dosage—emerges as a potential treatment for such neurological disorders (pages 1407–1413).

The gold standard for early detection of prostate cancer, PSA, has recently come under fire for its high rate of false positives. Virginia Hughes investigates some of the researchers hunting for better alternatives and asks whether their promises of creating viable—and profitable—biomarker tests will ever be realized.

Idiopathic pulmonary fibrosis, or lung scarring, is known, at least in part, to be driven by TGF-β signaling. Shuh Narumiya and colleagues now find that prostaglandin F_2α receptor also has a key role in this disease, independently of TGF-β signaling, and that its genetic deletion ameliorates disease progression in a mouse model.

Gökhan Hotamisligil and his colleagues report that reducing endoplasmic reticulum stress in macrophages by targeting the lipid chaperone aP2 ameliorates atherosclerosis in a mouse model, paving the way for a possible new clinical therapy.

Contrary to the widely held view that impaired γ-aminobutyric acid (GABA)-mediated neurotransmission underlies epileptic activity, extrasynaptic GABA-dependent thalamocortical inhibition caused by reduced GABA uptake is reported to be increased in diverse models of absence seizures.

Gallo and his colleagues report that commensal bacteria on the skin help to dampen inflammation caused by skin injury in mice. They show that, after wounding, necrotic cells release RNA that triggers TLR3 on keratinocytes, causing inflammatory cytokine release. Commensal bacteria in the skin suppress this inflammatory response through triggering TLR2 on the keratinocytes.

Excitotoxicity mediated by over activation of glutamate receptors results in neuronal loss after ischemia. Activation of sterol regulatory element–binding protein-1 is now shown to be crucial for glutamate-mediated excitotoxic neuronal death in a mouse model of stroke.

Adverse events stemming from the use of retroviral vectors in humans has prompted the search for methods predicting the fate and biological consequences of gene-modified cells after vector insertion. Methods of integration site analysis, such as linear amplification-mediated PCR (LAM-PCR), rely on use of restriction enzymes and identify only a fraction of all genomic integrants. This report describes a non–restriction enzyme–based LAM-PCR technique that provides comprehensive, unbiased integration site analysis.