In This Issue

doi:10.1073/iti0936106

New Research In

CHEMISTRY, BIOCHEMISTRY

Signaling enzymes detect damaged DNA

A set of base excision repair (BER) enzymes constantly survey DNA, correcting errors and mutations that arise during replication or because of mutagens. Whereas these enzymes are vital to health, mutations in BER enzymes are linked to a predisposition to various cancers. Although previous research has reported on how the enzymes repair DNA, it is not known how the enzymes detect damaged DNA. Some studies have hypothesized that these repair enzymes move along the DNA, feeling for breaks in the DNA strands, but there are too few enzymes for this surveillance strategy to be effective. Amie Boal et al. suggest that the enzymes use long-distance signaling to locate damaged DNA. The authors report that an iron-sulfur cluster, which is nestled inside many repair enzymes, is vital for this communication. Boal et al. suggest that the iron-sulfur cluster sends and receives redox signals through the DNA, enabling the repair enzymes to identify DNA damage. Mutations affecting the electronic coupling between the proteins and DNA interfere with DNA-mediated signaling between clusters and prevents the enzymes from communicating and triggering repair, increasing the risk of cancer, according to the authors. — B.P.T.

“Redox signaling between DNA repair proteins for efficient lesion detection” by Amie K. Boal, Joseph C. Genereux, Pamela A. Sontz, Jeffrey A. Gralnick, Dianne K. Newman, and Jacqueline K. Barton (see pages 15237–15242)

SOCIAL SCIENCES

Mobile phone data and relationships

Researchers interested in interpersonal relationships have long relied on self-reported data, which can be unreliable and time-consuming to collect. Nathan Eagle et al. used behavioral data to study how individuals interact. The authors provided 94 university students and faculty members with mobile phones enhanced with software that recorded information about calls, text messages, and proximity of the caller to the people contacted. Mobile phones gave a more accurate measure of information than the self-reported data, the authors found. In addition, the authors saw patterns of calls and proximity that allowed them to infer who a person's friends were with a 95% accuracy rate. The authors also found that people's calling patterns while at work—the more they called others, the less satisfied they were—matched self-reports of job satisfaction, suggesting that collecting information on relationships by using mobile phone data may prove a powerful and accurate alternative to the use of self-reported data, according to the authors. — B.A.

Data visualization of social network analysis.

“Inferring friendship network structure by using mobile phone data” by Nathan Eagle, Alex (Sandy) Pentland, and David Lazer (see pages 15274–15278)

MEDICAL SCIENCES

Long-term effects of low-carb diet

Diets that reduce carbohydrate intake while increasing protein and fat consumption often lead to significant weight loss in obese individuals. But according to a study with mice, these low-carb diets may have negative cardiovascular effects, such as cholesterol levels or markers of inflammation. Shi Yin Foo et al. report that a low-carb diet can induce vascular damage that is not immediately apparent. Unlike mice on a standard diet, mice on a low-carbohydrate, high-protein diet developed increased atherosclerotic buildup in their heart vessel walls and showed impaired vessel growth in response to vessel damage. Despite this atherosclerotic buildup and damage, the serum markers for measures of cholesterol and inflammation were no different from mice on a standard “western” diet. The authors found decreased levels of vascular progenitor cells, unusual because blood vessel growth was not known to be regulated by any dietary intervention, according to the authors. — T.H.D.

Effects of a low-carbohydrate, high-protein diet on atherosclerosis.

“Vascular effects of a low-carbohydrate high-protein diet” by Shi Yin Foo, Eric R. Heller, Joanna Wykrzykowska, Christopher J. Sullivan, Jennifer J. Manning-Tobin, Kathryn J. Moore, Robert E. Gerszten, and Anthony Rosenzweig (see pages 15418–15423)

MEDICAL SCIENCES

Humans metabolize folic acid slowly

The human liver is extremely slow to convert folic acid into its active form, researchers have found. The results may be related to the limited and inconsistent success of clinical trials using high doses of folic acid. Folic acid, which is not present in fresh foods to a significant extent, is a synthetic, inactive precursor that must be converted to physiologically active tetrahydrofolate by dihydrofolate reductase (DHFR). Steven Bailey and June Ayling measured the activity of DHFR in fresh samples of human liver with folic acid as substrate, and found it to be more variable and, on average, 56× lower than in rat livers. The authors say that human DHFR will likely be quickly saturated by folic acid doses above the US Daily Value, with higher intake providing little further increase of active folate. Although the intake of folic acid recommended for women of childbearing age is known to help prevent neural tube birth defects, the authors say that doses of folic acid above the US Daily Value may provide little additional benefit, and that extended exposure to unmetabolized folic acid also has been proposed to exacerbate other disorders. — P.D.

“The extremely slow and variable activity of dihydrofolate reductase in human liver and its implications for high folic acid intake” by Steven W. Bailey and June E. Ayling (see pages 15424–15429)