News & Views in 2012

Mechanisms triggering methicillin-resistant Staphylococcus aureus (MRSA) epidemics are poorly understood. A recent study provides new evidence that horizontal gene transfer may be the culprit for the emergence of new resistant and virulent MRSA clones.

The normally harmless behavior of bacteria in the intestinal tract is maintained by community structure and the integrity of host defenses. When either or both of these are compromised, a few disgruntled outcasts can cause a riot, taking down the whole neighborhood (pages 799–806).

A new study using a mouse model of lung diseases is the first demonstration in vivo that bone marrow–derived stromal cells can repair tissue injury through the transfer of mitochondria (pages 751–758). This suggests that rescue of injured cells through mitochondrial transfer may be an important process in many diseases.

Clinicians note that bariatric operations can dramatically resolve type 2 diabetes, often before and out of proportion to postoperative weight loss. Now two randomized controlled trials formally show superior results from surgical compared with medical diabetes care, including among only mildly obese patients. The concept of 'metabolic surgery' to treat diabetes has taken a big step forward.

Alternative splicing ensures the expression of functionally diverse proteins from individual genes; however, aberrant mRNA splicing is associated with various conditions, including heart disease. A recent study provides new mechanistic insights into heart failure by showing that a human cardiomyopathy-linked mutation in a cardiac splice factor affects post-transcriptional regulation, causing the expression of anomalous isoforms of a whole network of cardiac proteins (pages 766–773).

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. AMD progression is associated with alterations in inflammatory pathways and the immune system. A new study identifies a protective role for inflammasomes in AMD, suggesting that inflammasome activation might be manipulated as a potential therapeutic strategy for this condition (pages 791–798).

Liver injury promotes the outgrowth of cell types that are relatively rare in healthy livers, including progenitors and stromal cells. A new study shows that the type of injury influences the cellular composition of the liver progenitor niche, which then seems to direct the fate of progenitors during regeneration (pages 572–579).

Changes in gut microbial composition have been linked to inflammatory bowel disease, obesity and allergies in humans. A new study shows that pattern recognition of commensal bacteria by B cells reduces allergic inflammation in mice, adding to the mounting evidence for the 'hygiene hypothesis' (pages 538–546).

Cancer genome sequencing projects focus exclusively on the discovery of somatic changes. A new study shows that germline alterations in the proapoptotic protein BIM can have a crucial role in how a tumor responds to treatment (pages 521–528).

A recent study provides new insights into the central control of energy balance and obesity, showing that feeding behavior in mice can be modulated by local dendritic translation of a key protein in neuronal plasticity brain-derived neurotrophic factor (pages 564–571).

Vitamin E is commonly taken as a dietary supplement because it has been shown to have cardioprotective effects. However, its effects on bone metabolism are unknown. A new study in mice shows that α-tocopherol, the main isoform of vitamin E, stimulates bone osteoclast fusion independently of its antioxidant activity, resulting in increased bone resorption (pages 589–594).

Combination-based antiretroviral therapy has been very successful in preventing disease progression in HIV-infected individuals. However, a rational method for predicting the effect of a particular drug combination on clinical outcome is needed. A new study takes us closer to this goal by computationally predicting the inhibitory effects of combinations of three antiretroviral drugs (pages 446–451).

Kinase inhibitors are now standard treatment for patients with lung cancer whose tumors harbor specific mutant kinases. Four recent studies, including three in this issue (pages 375–384), have identified new fusion proteins involving another receptor tyrosine kinase that may potentially be responsive to existing targeted therapies.

Researchers have isolated a rare population of germline stem cells from adult mouse and human ovaries that are capable of forming oocytes. The ability to harvest such cells from human ovaries could change the options available for fertility preservation and the treatment of infertility (pages 413–421).

The kinase AKT has been regarded as an obligate intermediate in the insulin signaling pathway that suppresses glucose production by inhibiting the transcription factor forkhead box O1 (FoxO1) after meals. A new study shows that, without AKT-FoxO1 signaling, insulin still contributes to postprandial responses, revealing an AKT-independent pathway for insulin action that might be exploited to treat metabolic disease (pages 388–395).

New strategies for selectively stimulating bone formation without promoting bone resorption are required, as all currently approved agents for osteoporosis act on both of these aspects of the bone remodeling process. A recent study describes an approach that specifically delivers therapeutic siRNAs to bone-forming surfaces without affecting bone resorption (pages 307–314).

Some individuals with colorectal cancer benefit from therapies targeting the epidermal growth factor receptor (EGFR). However, resistance to EGFR blockade inevitably occurs. The characterization of a new mechanism of resistance to the EGFR-specific antibody cetuximab provides clues into how therapeutic strategies might be designed to overcome this specific resistance mechanism (pages 221–223).

Why do some influenza infections cause fatal disease and others barely a sniffle? Although viral virulence can vary, the immunological history of the host is also important. A new study in humans suggests that CD4⁺ T lymphocytes activated during previous infections can limit disease severity in the absence of specific antibodies (pages 274–280).

A new study shows that mice lacking tau develop parkinsonism because of intracellular iron accumulation that results in degeneration of dopamine neurons. Tau deficiency seems to impair ferroportin iron export by retention of the amyloid precursor protein, a neuronal ferroxidase partner, inside the endoplasmic reticulum (pages 291–295).

Noise-induced hearing loss is caused primarily by damage to auditory hair cells; however, humans are unable to regenerate damaged hair cells, necessitating the development of new therapeutic strategies to protect auditory hair cells. A new study suggests that the use of phosphodiesterase 5 (PDE5) inhibitors may provide a protective therapeutic route for hearing loss (pages 252–259).