In This Issue

ENGINEERING, DEVELOPMENTAL BIOLOGY

Plasticity of the stem cell nucleus

Lamins A and C lend stiffness to the cell nucleus but are not expressed in stem cells until gastrulation. Therefore, stem cell nuclei are physically much less stiff than differentiated cells. This property may make it easier for stem cells to migrate, adopt different shapes, and remodel nuclear DNA. David Pajerowski et al. characterized nuclear deformation in stem cells and an epithelial analog. The authors applied suction to cells by using micropipettes and studied nuclear shear by using fluorescence microscopy. Embryonic stem cells were the most deformable, followed by hematopoietic stem cells (HSCs) that also lack lamins A and C. Deformation followed a power law as a function of time: for the first 10 s, the exponent indicated a viscoelastic flow, which was followed by a phase of plastic, irreversible deformation. To verify that lamins were responsible for stiffness, the authors developed a line of epithelial cells in which lamin expression had been knocked down by 85%. Initially, the epithelial cells had been as stiff as any differentiated cell; without the lamins, they became as pliable as HSCs. The authors also investigated the flow properties of highly condensed chromatin, using GFP-histones to observe the irreversible distortion that occurs at long timescales.—K.M.

Photobleaching reveals stem cell chromatin flow.

“Physical plasticity of the nucleus in stem cell differentiation” by J. David Pajerowski, Kris Noel Dahl, Franklin L. Zhong, Paul J. Sammak, and Dennis E. Discher (see pages 15619–15624)

EVOLUTION

New challenges for conservation

When two different species interbreed, the resulting hybrids may be more or less fit than either parent. Benjamin Fitzpatrick and Bradley Shaffer investigated the evolutionary fitness of hybrid salamanders in California, where one such species is threatened and the hybrid population poses questions for conservation. In the Salinas Valley, Barred Tiger Salamanders, introduced >50 years ago, interbreed with native, and threatened, California Tiger Salamanders. To determine how the hybrid offspring change the population, the authors genotyped larvae and tracked their viability. Using data from five wild populations, the authors found that hybrids were more likely to survive than larvae from either single species population. Rather than showing hybrid dysfunction or an advantage of genes inherited from one species, the surviving hybrids had more evenly mixed genomes, implying that genetically mixed salamanders are likely to succeed and spread in California. The results show that hybridization can change the evolutionary process by infusing new genetic advantages to the hybrid populations. The effect of the hybrid salamanders on conservation decisions, however, depends on whether the goal is to ensure the survival of the native genome in its native habitat or the survival of a mixed, but possibly superior, population.—T.H.D.

“Hybrid vigor between native and introduced salamanders raises new challenges for conservation” by Benjamin M. Fitzpatrick and H. Bradley Shaffer (see pages 15793–15798)

EVOLUTION

Tug-of-war between natural and artificial selection

In commercial fisheries, harvesting is associated with reduced age and size in mature fish. The population responds to artificial selection in concert with natural selection. In the case of pike, the two are opposed: large size favors pike in sexual competition and cannibalism. Eric Edeline et al. document the “dynamic tug-of-war” between the influences on pike in Windermere Lake, in northern England, over a 50-year period. Starting in 1944, an effort was made to net the largest pike to reduce their numbers. Scientists collected data on both pike and perch populations until 1995. Cross-sections of opercular (gill cover) bones, analogous to tree growth rings, provide information on yearly growth. The authors use these data and a mathematical model to extrapolate the size of the fish caught to the maximum size they would have attained. Four phases were apparent in the period 1944–1995, with pike size alternately shrinking and growing depending on the intensity of the harvest, availability of prey, and intraspecies competition. The authors also find that females invest less energy in reproduction, and are thereby enabled to grow larger, during periods in which natural selection dominates. It is likely, the authors conclude, that pressure from commercial fisheries induces rapid evolution in a harvested population.—K.M.

Windermere Lake study area in northwest England.

“Trait changes in a harvested population are driven by a dynamic tug- of-war between natural and harvest selection” by Eric Edeline, Stephanie M. Carlson, Leif C. Stige, Ian J. Winfield, Janice M. Fletcher, J. Ben James, Thrond O. Haugen, L. Asbjørn Vøllestad, and Nils C. Stenseth (see pages 15799–15804)

MEDICAL SCIENCES

More genes for asthma

Airway inflammation and epithelial remodeling are two key features of asthma. Prescott Woodruff et al. report on some of the genes that are responsible for these changes. The authors compared gene expression profiles of airway epithelial cells taken from asthmatic subjects, healthy subjects, and habitual smokers. After analyzing the gene expression on microarray chips, they found that CLCA1, periostin, and serpinB2 were up-regulated in asthma but not in smokers. Corticosteroid treatment in the asthmatic subgroup down-regulated expression of these three genes and up-regulated expression of FKBP51. A high baseline of the three up-regulated genes was associated with a good response to corticosteroids, whereas high amounts of FKBP51 predicted a poor response. When epithelial cells were cultured, the authors found that IL-13 increased the expression of the three genes and the corticosteroids prevented it. The steroids also induced the expression of FKBP51. The authors say their results show that airway epithelial changes in asthma are distinct from those in smokers and that the genes they have identified are candidate mediators of asthma and markers of steroid responsiveness.—P.D.

Periostin protein expression in biopsy from a subject with asthma.

“Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids” by Prescott G. Woodruff, Homer A. Boushey, Gregory M. Dolganov, Chris S. Barker, Yee Hwa Yang, Samantha Donnelly, Almut Ellwanger, Sukhvinder S. Sidhu, Trang P. Dao-Pick, Carlos Pantoja, David J. Erle, Keith R. Yamamoto, and John V. Fahy (see pages 15858–15863)

MICROBIOLOGY

Microbial cheaters

The bacterium Pseudomonas aeruginosa relies on quorum sensing, the use of chemical signals to coordinate cell density-dependent behavior, to induce the expression of virulence factors. At the top of the system that regulates quorum sensing is the gene lasR, which encodes the receptor for the diffusible signal that controls group behavior. Kelsi Sandoz et al. now report that some P. aeruginosa are lasR mutants that make no metabolic investment in quorum sensing but nonetheless reap the benefits. These mutants are “social cheaters.” The authors found that lasR mutants emerge after ≈100 generations of growth in minimal medium containing caseinate as the sole carbon source. Protease factors expressed during quorum sensing are required for the bacteria to break down caseinate. When there are too many cheaters, the entire population pays the price in the form of reduced growth and decreased production of quorum-controlled factors. However, quorum sensing itself provides the environment in which the cheaters have a selective advantage. When the constituent amino acids of caseinate provide the carbon source, cheaters do not emerge. Because lasR mutants have been isolated in many P. aeruginosa infections, the authors say that quorum sensing may be a potential target for antibiotic therapy.—K.M.

“Social cheating in Pseudomonas aeruginosa quorum sensing” by Kelsi M. Sandoz, Shelby M. Mitzimberg, and Martin Schuster (see pages 15876–15881)

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