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A new regulatory pathway established last year allows drugs with dramatic early clinical promise to be expedited to the market quicker than ever before. To date, most of these 'breakthrough' designations have gone to cancer agents, raising the prospect of faster access to the latest lifesaving therapies for the estimated 4,500 people newly diagnosed with cancer each day in the US. Elie Dolgin looks at what sets these breakthrough medicines apart.

Humans lack robust regeneration of hair follicles after skin wounding. George Cotsarelis and colleagues now show that γδ T cells are not present at high levels in human skin, that in mice they are a key initial source of the protein fibroblast growth factor 9 and that this factor modulates hair follicle regeneration during skin wound healing. These results suggest a possible topical clinical treatment to regrow hair after wounding and perhaps for other conditions of hair loss.

Building on earlier work, Dekkers et al. describe the first application of their intestinal organoid culture technology to the study of human disease, in this case cystic fibrosis. These so called 'mini-guts', which recapitulate the essential in vivo intestinal tissue architecture in vitro, are used to develop a rapid and quantitative assay to measure mutant cystic fibrosis transmembrane conductance regulator (CFTR) function, as well as test the efficacy of correctors and potentiators of mutant CFTR.

Monocytes play an important part in the clearance of pathogens during infection. Yasmine Belkaid and her colleagues now report that inflammatory monocytes can also have a regulatory role. Specifically, these cells can mitigate the tissue damage induced by neutrophils during infection of mice with Toxoplasma gondii by releasing prostaglandin E2 in response to commensal bacteria.

Nitric oxide donors protect from myocardial ischemia-reperfusion injury, but the underlying mechanisms have been unclear. Edward T Chouchani et al. uncover the molecular target of such donors, a cysteine residue in a subunit of complex I of the mitochondrial respiratory chain, and suggest that this cysteine residue has a general role in regulating complex I activity and modulating ischemia-reperfusion injury.

Lipid droplets have a key role in the assembly of hepatitis C virus (HCV) particles in liver cells. Jake Liang and colleagues now report that a host factor, IκB kinase-α is required for efficient production of HCV by increasing cellular lipid droplet content through its regulation of lipogenic genes in infected cells. The findings provide insight into some of the metabolic changes induced by HCV infection and may offer a new potential therapeutic target.

Glucagon has traditionally been thought to act exclusively on the liver to promote endogenous glucose production in that organ. Tony Lam and his colleagues now show that it also acts on the hypothalamus to inhibit glucose production through a neural relay to the liver and that under high fat–fed conditions in rats this pathway is inhibited. This resistance may further explain the hyperglycemia that exists during obesity and diabetes.

Pierre Guermonprez and colleagues have worked out how a subset of dendritic cells expands in individuals with severe malaria. Plasmodium infection causes an accumulation of xanthine in infected red blood cells. The researchers found that type I interferon triggers an increase in the enzyme that metabolizes xanthine to uric acid. Uric acid then acts on mast cells to release Flt3 ligand, an important regulator of dendritic cells, which in turn stimulate T cells to respond to the infection.

Osteoarthritis has been believed to be caused by improper mechanical function of articular joints. Xu Cao and his colleagues now show that this mechanical process leads to upregulation of transforming growth factor β1 activity in mesenchymal stem cells of subchondral bone, resulting in aberrant bone formation, further destabilization of the joint and ultimately the onset of the disease.

Abnormalities in how pulmonary veins connect to the heart underlie a type of congenital heart disease. Jonathan Epstein and his colleagues show that this condition, termed anomalous pulmonary venous connections, can be caused by mutation of the gene encoding the guidance protein semaphorin 3d and show how this protein acts in the embryo to pattern the developing pulmonary veins.

Marsilius Mues et al. have overcome previous obstacles precluding the expression of genetically encoded calcium indicators (GECIs) in immune cells by developing a new fluorescence resonance energy transfer–based GECI for the functional calcium imaging of T cells in vivo. Using two-photon imaging, the group traced the real-time activation of T cells in peripheral lymph nodes after antigen application, as well as in the CNS during experimental autoimmune encephalomyelitis.