Editors' Choice

Science  08 Jun 2012:
Vol. 336, Issue 6086, pp. 1211
  1. Ocean Science

    Acid Test

    1. H. Jesse Smith

    Fossil fuel use increases the concentration of carbon dioxide in the atmosphere and thence the oceans, lowering ocean pH. The resulting equilibria diminish the available carbonate that calcifying organisms precipitate as the calcium salt, a problem that has led to a general assumption that calcifying organisms accordingly will decrease in abundance. However, recent research has shown that not all types will be affected equally, or even in the same way. Smith et al. studied how the coccolithophore species Emiliania huxleyi responds to seasonal changes in the Bay of Biscay. By collecting abundance data and making concurrent measurements of carbonate chemistry over the course of a year, they showed that the more heavily calcified morphotype is most abundant in winter, when the ocean there is most acidic, opposite from what one might predict on the basis of pH changes. Although they cannot attribute this variability to pH-related effects, their work illustrates just how difficult it is to project precisely how specific calcifying processes will respond to an acidifying ocean.

    Proc. Natl. Acad. Sci. U.S.A. 109, 10.1073/pnas.1117508109 (2012).

  2. Physiology

    You Are When (Not What) You Eat

    1. L. Bryan Ray

    Mammals synchronize their metabolism with daily cycles of eating and activity, and disruption of such patterns has deleterious effects on metabolism. Hatori et al. explored whether such disruption may affect diet-induced obesity in mice. Mice are nocturnal, so they normally have peaks of food intake, activity, and energy expenditure during the night. Mice allowed unlimited access to a high-fat diet, however, had blunted rhythms, fasted for a shorter time, and ate during a greater proportion of the day. They also got fat and showed signs of metabolic disease. However, when the authors controlled the timing of eating so that the mice on the high-fat diet ate only during the night, they ate as much as the unrestricted animals did, but did not become obese, retained sensitivity to insulin, and avoided hepatic steatosis and inflammation that plagued the fat mice. Restricted food consumption in tune with the circadian cycle may have inhibited gluconeogenesis and instead favored glycolysis, reduction of glutathione, and anabolic processes. Whether such results will also apply to humans remains to be determined, but changing when you eat rather than what you eat may be a lot easier to implement.

    Cell Metab. 15, 10.1016/j.cmet.2012.04.019 (2012).

  3. Genomics

    Showers of Mutations

    1. Paula A. Kiberstis

    Systematic cataloging of somatic mutations in cancer genomes not only helps identify specific genes driving tumor development but can also potentially reveal clues to the endogenous or environmental factors that caused the mutations in the first place. Lung and melanoma genomes, for example, have mutational patterns characteristic of tobacco carcinogens and ultraviolet light, respectively. Nik-Zainal et al. have begun to explore the mutational processes operative in human breast cancer. By documenting the full repertoire of somatic mutations in 21 different tumors and using mathematical approaches to classify them, they discovered that single-nucleotide substitutions in breast cancer appear to be generated by at least five independent mutational processes. Mutations were more prevalent in genes expressed at low levels. Most of the tumors exhibited regional clusters of hypermutation (called “kataegis,” Greek for shower), which were closely associated with regions of chromosomal rearrangements. The authors hypothesize that these mutations are caused by the AID/APOBEC family of cytidine deaminases, which generate somatic hypermutation in the immune system.

    Cell 149, 979 (2012).

  4. Microbiology

    Hygiene Can Hurt

    1. Caroline Ash

    As human societies urbanize, chronic inflammatory disorders become more apparent. The hygiene hypothesis suggests that individuals exposed to infection in childhood are less likely to develop inflammatory disease because exposure to microorganisms is important for stimulating responses that maintain epithelial cell integrity. Hence, in urban environments, reduced contact with the full diversity of the microbial world may be leading to the increased incidence of inflammatory disorders. Hanski et al. took a random sample of 118 adolescents from towns, villages, and isolated dwellings in eastern Finland, tested their immune function and allergic responses, surveyed their skin microflora, and investigated the biodiversity within their homes. They found several significant correlations, not least that low biodiversity was surprisingly strongly associated with atopy, and concluded that humans need to interact with natural environments for their physical health, not just for their peace of mind.

    Proc. Natl. Acad. Sci. U.S.A. 109, 10.1073/pnas.1205624109 (2012).

  5. Microbiology

    When Microbes Go Rogue

    1. Kristen L. Mueller

    In the gut, maintaining the peace is key—we live symbiotically with the trillions of microbes that inhabit this space, and rarely do any problems arise. But disruptions to this peace, as in the form of antibiotics, have the potential to cause disease. Ayres et al. explored this by treating mice with antibiotics and a chemical that causes colitis by disrupting gut epithelial cell integrity. Surprisingly, antibiotic- and chemical-treated mice did not develop colitis—instead, they developed a lethal, sepsis-like disease. Investigation into what caused septicemia in the mice revealed that it was the result of the outgrowth of an antibiotic-resistant strain of Escherichia coli that is normally present in the guts of healthy mice in small amounts. In accordance with Koch's postulates, injection of this strain of E. coli caused a sepsis-like disease in mice that were not treated with antibiotics or the colitis-inducing chemical. Disease depended on the Naip5-Nlrc4 inflammasome complex, which did not regulate bacterial growth but rather promoted immunopathology. This study illuminates how some microbes that we normally harbor without a problem can “go rogue”—with devastating effects—when the normal peace is disturbed.

    Nat. Med. 18, 799 (2012).

  6. Materials Science

    Cell Versus Gel

    1. Marc S. Lavine

    The physical properties of a substrate are known to affect the fate of stem cells by influencing whether they spread out and remain potent, or whether they undergo differentiation. In vivo, for example, human epidermal stem cells can adhere to the extracellular matrix (ECM), which regulates the differentiation depending on which signaling molecules are present. Trappmann et al. show that this picture needs to be expanded to include not just the substrate stiffness but the way in which the cells interact with and alter the underlying material. They prepared polydimethylsiloxane (PDMS) substrates with varying stiffness to which collagen-I was directly coupled to avoid issues of ECM remodeling. For both epidermal cells and human mesenchymal cells, the stiffness did not affect the cell spreading or differentiation. However, this was not the case for cells seeded on collagen-I attached to polyacrylamide (PAAm) hydrogels. For very soft gels, cells could not form stable focal adhesions, leading to differentiation. The authors noted that for the PAAm hydrogels, changes in stiffness correlated with changes in porosity, which in turn affected the density of the attached collagen-I. By varying either the strength of the collagen-I attachment at a fixed density, or the density with a fixed underlying substrate stiffness, they confirmed that the level of feedback between the gel properties and the adhered cells strongly affected cell fate.

    Nat. Mater. 11, 10.1038/NMAT3339 (2012).

  7. Physiology

    The Good Interred in Bones

    1. Brooks Hanson

    Our bones are constantly being replaced through a process of resorption and regrowth. This requires a healthy blood supply to the bones, which also transports necessary elements. Bones are the main reservoir of calcium in the body, and they favor the lighter calcium isotopes. In an experiment with patients undergoing bed rest, which drives gradual bone resorption, Morgan et al. show that assaying the isotopic distribution of calcium in urine (which is derived primarily from the residual calcium in soft tissues) can detect changes in the balance of bone mineralization more rapidly than other standard approaches. They quantify the loss in a physiological model that includes further isotope fractionation occurring in the kidneys. Separately, Jaouen et al. show that measuring both iron and copper isotopes in archaeological bone samples can be used to determine an individual's gender—an otherwise major challenge if certain distinguishing bones (e.g., pelvis) aren't preserved. Here, the isotope fractionation occurs elsewhere in the body, and differently in men and women, and the bones harbor these elements.

    Proc. Natl. Acad. Sci. U.S.A. 109, 10.1073/pnas.1119587109 (2012); Am. J. Phys. Anthropol. 10.1002/ajpa.22053 (2012).