Articles in 2014

The concordant epidemics of asthma and obesity are both associated with inflammation, and obesity has been shown to be an independent risk factor for asthma. A new study in mice indicates that part of the immunological connection between obesity and asthma involves inflammasome activation and production of the cytokine interleukin-17 by innate lymphoid cells in the lung (pages 54–61).

Under most circumstances, Foxp3⁺ regulatory T (T_reg) cells are a stable T cell population essential for maintaining self-tolerance. A study now shows that the inflammatory environment in autoimmune arthritis induces conversion of a subset of Foxp3⁺ T cells into interleukin-17–producing cells that contribute to disease pathogenesis (pages 62–68).

Many tumors display a hierarchical organization that is maintained by a self-renewing 'cancer stem cell' population. A new study in mice shows that targeting the self-renewal regulator BMI-1 abrogates the tumorigenic capacity of colon cancer stem cells, providing a new therapeutic strategy (pages 29–36).

Metabolic regulators that permit adaptation to changes in caloric intake have been shown to be needed to protect from age-related disorders. Sirtuins play a crucial part in this program, impinging on not only aging but also other diseases. New findings are uncovering the multifaceted activity of sirtuins in living organisms and their effects on healthspan. In 'Bedside to Bench', Leonard Guarente discusses how different sirtuins are hindering cancer metabolism through suppression of the Warburg effect. The apparent antitumor effects of several sirtuins through their regulation of different metabolic pathways suggest therapeutic approaches to induce sirtuin function or that of downstream targets may block cancer growth. In 'Bench to Bedside', Eric Verdin peruses a few studies in different animal models showing that increased amounts of nicotinamide adenine dinucleotide (NAD), a cofactor of sirtuins, may have a positive effect in longevity and span of healthy life, or healthspan, by increasing sirtuin enzymatic activity. Whether harnessing NAD therapeutically is a potential way to extend lifespan and ameliorate diseases is still open to debate.

The problem of inequity in international research is perpetuated by policies that enable scientists to conduct research in lower-resourced areas of the world without partnering with local researchers. The World Health Organization (WHO) needs to lead in solving this problem by working with research institutions, journal editors and funding agencies to document the degree of inequity and to impose penalties for failures to collaborate.

Liver-stage Plasmodium infection triggers a type I interferon transcriptional program in hepatocytes that amplifies an innate immune response within hepatic myeloid cells. This minimizes liver parasite load and delays the release of disease-causing parasites into the bloodstream (pages 47–53).

Reproducibility in science is a prominent topic in both lay and scientific press. But a new facet of this discussion has arisen in a recent comparison of two pharmacogenomic studies, and it calls for an evaluation of how we interpret science in the face of discrepant results.

Insulin-producing islet cells could hold the secret to curing type 1 diabetes—if only scientists could figure out a way to encapsulate and transplant them into the body. But first, the right biocompatible material must be found to hold these precious cells. A team of bioengineers thinks it has discovered one. Elie Dolgin reports.

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.

On 27 January, the US National Institute on Alcohol Abuse and Alcoholism (NIAAA) will welcome George Koob as its new permanent head. A neurobiologist at the Scripps Research Institute in La Jolla, California, for the past 30 years, Koob, 66, made his name both in the study of alcoholism and in addiction to other substances. His work has long been funded by both NIAAA and NIDA. Elie Dolgin spoke with Koob about what he thinks sets alcohol research apart.