News & Views in 2010

Thalidomide, a drug reviled in the 1960s for its teratogenic effects, has been revived in recent years for cancer and leprosy therapy. A study now finds another use for this drug in vascular disease, providing further insights into the drug's mechanisms of action (pages 420–428).

Two reports in this issue identify a link between insulin action and the unfolded protein response—a pathway that helps the endoplasmic reticulum cope with cellular stress (pages 429–437 and 438–445). The results expand our understanding of the pathogenesis of insulin resistance and provide new targets for prevention and treatment of obesity.

Fewer than half of patients with multiple sclerosis respond to interferon-b, one of the most widely prescribed therapies. The discovery that different subtypes of T cells may be involved in disease development in each affected individual suggests that it may be possible to predict therapeutic success by determining a patient's cytokine profile (pages 406–412).

Galectins are carbohydrate-binding proteins with diverse activities, but there is no unifying picture of their primary physiological role. Galectins now emerge as autonomous bacteria-killing agents (pages 295–301), unexpected findings that may point to a principal role of these proteins in innate immunity.

Systemic inflammation results in a life-threatening drop in blood pressure. Targeting known players of blood pressure regulation has so far failed to improve outcomes for individuals with sepsis. But a study points to a regulatory pathway involving the amino acid metabolite kynurenine that may provide new avenues for therapies (pages 279–285).

Altered lipid metabolism underlies the production of excess mucus in a mouse model of cystic fibrosis (313–318). The findings point to the nuclear receptor peroxisome proliferator–activated receptor-γ (PPAR-γ) as a potential therapeutic target in this disease.

Serotonin produced in the gut reduces the formation of bone. This biology is now harnessed with an orally available inhibitor of gut serotonin synthesis (pages 308–312). The inhibitor promotes bone formation in rodents and points the way to the development of much-needed bone-building drugs.

The involuntary muscle spasms that occur as a result of neuromotor disorders and spinal cord injury can have dangerous consequences for affected individuals. New findings shed light on one mechanism contributing to spasticity: limited chloride transport in motoneurons (pages 302–307).

The extraordinary diversity of HIV is a major barrier in the path of developing a vaccine. One way forward may be mosaic antigens—biometrically designed genes that maximize overlap between sequences used in the vaccine and circulating HIV-1 strains worldwide (pages 319–323 and 324–328).

Microbes in the gut can influence distant events, affecting the function of neutrophils in the circulation of mice (pages 228–231). The findings should lead to new studies examining how intestinal microbes affect immunity.

The receptor for interleukin-7 is a susceptibility factor in multiple sclerosis, but its exact role in the disease has been unclear. New findings outline a function for interleukin-7 in the biology of T helper 17 cells, a subset of T cells recently identified as key players in autoimmune disorders (pages 191–197).

Inflammatory cells can promote tumor cell proliferation, but the range of mechanisms has not been fully explored. A proteinase produced by neutrophils is now shown to enter tumor cells and promote their proliferation (pages 219–223).

One hazard of gene therapy is that the vector will insert into an inappropriate location, causing aberrant expression of genes that can lead to disease. A new study reveals how such events occurred in a recent gene therapy trial using a vector that has now fallen out of favor (pages 198–204).

Researchers have long known that the peptide angiotensin II is central to blood pressure control—but there is yet more to learn. A new study shows how angiotensin II cooperates with the JAK2 kinase, better known for its role in cytokine signaling, to regulate blood vessel contraction and influence blood pressure (pages 183–190).

Innate immune signals and p53 contribute to the 5q– myelodysplastic syndrome, an acquired bone marrow failure disorder (pages 49–58 and 59–66).

Susceptibility to Crohn's disease has been linked to polymorphisms in genes involved in two pathophysiological pathways: autophagy and the recognition of bacterial peptidoglycan by nucleotide oligomerization domain-2 (NOD2), an intracellular receptor. Two studies link these pathways by showing that recognition of bacterial peptidoglycans by NOD2 induces autophagy and bacterial clearance.

The neuronal accumulation of mutant huntingtin is a hallmark of Huntington's disease. New research shows that post-translational modifications of the mutant protein promote its clearance, uncovering new therapeutic targets for this disorder.

A common retrovirus encases itself in an extracellular matrix, enabling its transfer between T4 cells. The discovery of this new mode of infectivity has the potential to lead to new ways to combat the virus, human T cell leukemia virus type 1 (HTLV-1), which is associated with cancers and inflammatory disorders (pages 83–89).

Blood pressure oscillates with the circadian rhythm, and a molecular mechanism has now been discovered (pages 67–74). The results point to a new genetic risk factor for hypertension and to a potential new target against this condition.