Articles in 2014

New antibiotics are needed to treat drug-resistant Mycobacterium tuberculosis infections. Richard Lee and his colleagues now report a new series of semisynthetic spectinomycin analogs that show promise as potentially safe and effective antitubercular drug candidates.

In heart muscle cells, sarcoplasmic reticulum calcium overload leads to spontaneous calcium waves that can cause arrhythmias and sudden cardiac death. S.R. Wayne Chen and his colleagues now detail the molecular mechanism by which intra–sarcoplasmic reticulum calcium ions interact with the gate of the calcium release channel RyR2, explaining how calcium waves are initiated and thereby contribute to calcium-triggered arrhythmias.

In a new study by Kamran Atabai and colleagues, the milk fat globule protein, Mfge8, is found to promote the uptake of dietary fat and the absorption of fatty acids by peripheral organs via activation of integrin signaling and the expression of fatty acid transporters. They also found that genetic deletion of Mfge8 protected mice from diet-induced obesity and insulin resistance.

Retinoic acid and arsenic therapies have shown considerable efficacy in patients with acute promyelocytic leukemia, but their exact mechanism of action remains unclear. Here, Hugues de Thé and colleagues uncover a therapeutic effect mediated by nuclear body reformation and p53 activation that involves the induction of a senescence transcriptional program. These data suggest that redifferentiation and apoptosis induction may not be sufficient for the effect of these agents in patients and uncover alternative therapeutic routes that could be applied to other tumor and treatment types.

Monoclonal antibodies (mAbs) that bind the stalk domain of the influenza hemagglutinin glycoprotein have been shown to have broadly neutralizing activity against diverse influenza subtypes. In this study, DiLillo et al. report that, unlike strain-specific anti–hemagglutinin head domain mAbs, anti-stalk mAbs can mediate antibody-dependent cell cytotoxicity and require interactions with Fc receptors for their in vivo neutralizing activity.

Dietary fibers are metabolized by the gut microbiota into short-chain fatty acids (SCFAs) and have protective effects in inflammatory bowel disease. Here Benjamin J Marsland and colleagues report that mice fed a high-fiber diet have an altered microbiota and are protected from allergic airway inflammation. The SCFA propionate regulated allergic inflammation, bone marrow hematopoiesis and dendritic cell function. Taken together, these findings suggest that metabolites produced by the gut microbiota can influence hematopoiesis and immune responses in the lung.