Mother’s environment influences physical traits of ant offspring
Harvester ant (Pogonomyrmex rugosus) workers tending a larva.
Many plants and animals adapt to their environments by producing disparate physical traits from a single genotype, a phenomenon known as polyphenism. Mothers exposed to certain environmental conditions are known to produce phenotypically diverse offspring, leaving a trail of evolutionary clues that could help researchers unravel the survival strategies and life histories of certain species. Romain Libbrecht et al. (pp. 11050–11055) used a multipronged approach to explore this phenomenon in the seed-harvester ant, Pogonomyrmex rugosus, an insect known for its complex social structure. The authors collected P. rugosus queens during nuptial flights in Bowie, Arizona, and allowed the ants to establish colonies in the laboratory. Three years later, the authors studied the mature colonies to understand how the combined effects of environmental conditions and hormones influence the relative production of reproductive queens and sterile workers, groups that are morphologically different but share a genotype. The authors report that ant offspring develop vastly different phenotypes depending on the interplay between maternal insulin signaling, release of a reproductive hormone, and the expression of the vitellogenin gene, which influences egg yolk production. According to the authors, the study reveals how environmental conditions experienced by one generation can yield diverse physical traits in the next generation. — A.G.
A small molecule active against drug-resistant and persistent tuberculosis
Chemical structure of active compound.
Tuberculosis (TB) is a major global health problem, and developing drugs targeting drug-resistant and persistent forms of TB has been a challenge. Feng Wang et al. (pp. E2510–E2517) carried out a cell-based screen based on in vitro biofilm formation to identify compounds with previously undiscovered mechanisms of action that might be effective against drug-resistant and persistent Mycobacterium tuberculosis (Mtb). The authors identified a small molecule, TCA1, which significantly inhibited the growth of both drug-susceptible and drug-resistant Mtb, and sterilized Mtb in vitro in combination with the frontline TB drugs rifampicin (RIF) or isoniazid (INH). TCA1 showed bactericidal activity against both replicating and nonreplicating Mtb in vitro and was also effective in vivo in mouse models of acute and chronic Mtb infection, both alone and in combination with INH or RIF. Genome-wide transcriptional analysis revealed that TCA1 down-regulates genes known to be involved in Mtb dormancy and drug tolerance, and genetic and biochemical methods showed that TCA1 targets enzymes involved in cell wall and molybdenum cofactor biosynthesis. The findings indicate that cell-based screens of biofilm formation could help identify compounds effective against Mtb in vivo, and the authors suggest that TCA1 could lead to the development of drugs against persistent and drug-resistant Mtb. — S.R.
Resurrected DNA suggests universal common ancestor thrived at high temperature
Crystal structures of T. thermophilus and the resurrected ancestral NDKs. The hexameric-type structure shown in the figure for Arc1 and Bac1 (middle and right panels, respectively) has been found for extant NDKs including that from T. thermophilus (left panel).
To better understand the nature of our last universal common ancestor, researchers have used phylogenetic analysis to deduce the environmental temperature at which this organism must have lived. But such theoretical studies have produced conflicting results in the past. Satoshi Akanuma et al. (pp. 11067–11072) present experimental evidence that the last universal common ancestor, or “Commonote,” was a likely thermophile, which flourished at high temperatures. Using a technique to resurrect sequences for archaeal and bacterial ancestral nucleoside diphosphate kinase (NDK), ancient genetic code fragments still carried by most extant organisms, the authors constructed genes to encode the inferred products and expressed them in Escherichia coli. The authors then evaluated the heat stabilities of these proteins—roughly 110 degrees C—and estimated that the optimal environmental temperature for this ancient life form from around 3.8 billion years ago would have been 80–100 degrees C. Furthermore, mutagenesis experiments suggested that the Commonote also possessed a thermostable NDK, and because NDK stability is directly related to the environmental temperature, the authors suggest that the last common ancestor of all life on Earth was a likely thermophile. — T.J.
Molecular mechanism of smoking-induced bone loss
The smoke carcinogen BaP stimulates bone resorption in sections of vertebral bone from mice.
Cigarette smoking causes bone loss and increases the risk of osteoporosis and bone fracture. Smoking-induced bone loss has traditionally been attributed to impaired bone formation by cells called osteoblasts, but the effects of smoking on bone resorption by cells known as osteoclasts remain unclear. Jameel Iqbal et al. (pp. 11115–11120) investigated the effects of the smoke carcinogens benzo[a]pyrene (BaP) and TCDD, a type of dioxin, on osteoclastic bone resorption. The authors found that low concentrations of BaP or TCDD stimulate osteoclastogenesis—the development of osteoclasts—and bone resorption in cells grown in culture and in mice. By contrast, BaP-induced osteoclastogenesis was abolished in cells that lack the transcription factor Ahr, which is known to be activated upon binding BaP and TCDD. Furthermore, mice lacking Ahr displayed reduced levels of osteoclastogenesis and increased bone mass. Genetic deletion or pharmacological inhibition of Cyp1 enzymes, which are induced by Ahr activation, impaired basal levels of osteoclastogenesis and bone resorption in mice, and prevented TCDD-induced osteoclastogenesis in bone marrow cell cultures. The findings reveal that the smoke carcinogens BaP and TCDD increase osteoclastogenesis via AhR-mediated induction of Cyp1 enzymes, and suggest that Ahr may be a potential drug target to inhibit bone loss in smokers, according to the authors. — N.Z.