This Week in Science

Science  07 Sep 2012:
Vol. 337, Issue 6099, pp. 1146
  1. Understanding a Broken Heart

    1. Caroline Ash

    Cardiac myosin-binding protein C (cMyBP-C) is a thick filament–associated sarcomeric protein that modulates cardiac contractility in a phosphorylation-dependent manner; mutations in the MYBC3 gene are the leading cause of hypertrophic cardiomyopathy. Previs et al. (p. 1215, published online 23 August; see the Perspective by Burghardt and Ajtai) have isolated native myosin thick filaments from transgenic mouse hearts, which retained the spatial distribution of cMyBP-C in the thick filament. Imaging of a single actin filament being propelled along the thick filament showed that the N-terminal 29-kD domain of cMyBP-C slows actomyosin motion in parts of the thick filament corresponding to the C-zones in which the thick filaments are cross-bridged. This effect on actomyosin contractility was tuned by graded phosphorylation of four serines adjacent to the 29-kD domain. The findings may explain the appearance of a cMyBP-C fragment in the serum of patients with cardiac ischemia and why cMyBP-C haploinsufficiency associated with cardiomyopathy patients might trigger a hypertrophic response.

  2. Sensing Cell Size


    How cells sense and control the size of their constituent parts is poorly understood, but an understanding is vital for interpreting normal cell function. Chan and Marshall (p. 1186) discuss how cells can sense and regulate the size of their internal structures or organelles. For example, bacterial flagellae act as their own tape measures. In eukaryote cells, reporter molecules may monitor cell and telomere length, and in molecular scaffolds, conformational changes and occupancy times measure organelle size. Indirect size selection may arise from a loss of function with growth or scaling problems with processes like intracellular transport. Now, advances in imaging offer glimpses into the mechanisms of cell sizing and the consequences if this process goes wrong.

  3. Predictions of Genetic Disease

    Many genome-wide association studies (GWAS) have identified loci and variants associated with disease, but the ability to predict disease on the basis of these genetic variants remains small. Maurano et al. (p. 1190; see the Perspective by Schadt and Chang; see the cover) characterize the location of GWAS variants in the genome with respect to their proximity to regulatory DNA [marked by deoxyribonuclease I (DNase I) hypersensitive sites] by tissue type, disease, and enrichments in physiologically relevant transcription factor binding sites and networks. They found many noncoding disease associations in regulatory DNA, indicating tissue and developmental-specific regulatory roles for many common genetic variants and thus enabling links to be made between gene regulation and adult-onset disease.

  4. Skipping the Odds

    When confined to a plane and placed in a magnetic field at low temperatures, electrons are separated by energy into the so-called Landau levels; adding an extra electron after a Landau level that has been filled is costly. In some systems, electron-electron interactions cause the appearance of sublevels, in a phenomenon known as the fractional quantum Hall effect (FQHE). This effect has been observed in graphene, but the number of levels that had been resolved was limited. Feldman et al. (p. 1196) directly measured the change in the chemical potential caused by varying electron density, which is controlled by gate voltage. Once the FQH states were identified, the Landau levels with odd-numerator fractional fillings were found to be missing between filling factors 1 and 2, because of the broken and preserved symmetries of graphene. These observations help to explain how the FQHE in graphene is different from that observed in conventional semiconductors, and the technique will also allow local measurements to be made; hence, monitoring of spatial variations in sample behavior is possible.

  5. Enols in the Atmosphere?

    Keto/enol tautomerization (HC−C=O→C=C−OH) plays a central role in the chemistry of carbonyl compounds in a solution in which solvent and catalytic acids or bases can facilitate the proton transfer from C to O and back again. In contrast, analyses of atmospheric chemistry tend to exclude enol structure, on the assumption that tautomerization does not proceed regularly in gas phase. Andrews et al. (p. 1203, published online 16 August) used isotopic labeling to probe the photoisomerization pathway of gaseous acetaldehyde in the lab and discovered evidence for an enol. Subsequent modeling indicates that photogenerated enols could build up sufficiently in the troposphere to account for previously puzzling observations of organic acids in the atmosphere.

  6. Pinning Down Nuclear Shells

    The nuclei of heavy atoms are destabilized by proton repulsions, and, conversely, the quantum-mechanical shell effects help to stabilize them. There are theoretical models for predicting the masses of yet-to-be-discovered superheavy elements, based on such shell effects, and these models can be tested by studying the shells of known actinide nuclei. The problem is that current mass values determined from studying radioactive decay products have substantial errors. Minaya Ramirez et al. (p. 1207, published online 9 August; see the Perspective by Bollen) were able to collect a sufficient number of nuclei of lawrencium and nobelium isotopes in an ion trap to determine their masses directly by mass spectroscopy. These results will be helpful in predicting the heaviest possible element.

  7. Nighttime Sources


    Organic aerosols account for about half of the total mass of small (submicrometer) particles in the troposphere, and most of them are believed to form through the oxidation of volatile molecules, rather than being emitted directly from specific sources. These particles have important roles in many atmospheric processes, and therefore a better understanding of their complex composition and chemistry is desirable. Rollins et al. (p. 1210) report on measurements of particulate organic nitrates, an important class of organic aerosols that form at night. However, they also found that high concentrations of organic molecules can suppress the growth of organic nitrate particles. These observations should help improve efforts to reduce organic aerosol pollution.

  8. Responding to Light and Heat

    The protein rhodopsin is sensitive to dim light, but its sensitivity is limited by signals caused by the noise of thermal activation. The basis of this relationship, known as the Barlow correlation, has long been debated. A recent study suggested that thermal activation involves a canonical isomerization reaction. Gozem et al. (p. 1225) confirm that isomerization is the rate-limiting step controlling thermal noise, and they provide a molecular understanding of the Barlow correlation. They use quantum mechanics coupled with molecular mechanics to show that the transition state mediating thermal activation has the same electronic structure as the photochemical excited state.

  9. Toxic Neighborhood

    Bacterial populations are often considered to be driven by gene-centric, selfish dynamics. Superficially, antibiotic production fits this picture as individuals can gain most benefit by inhibiting or killing close relatives with high niche overlap. Contrary to that notion, Cordero et al. (p. 1228; see the Perspective by Morlon) show that bacteria in the wild form social units in which antibiotic production and resistance leads to cooperation within, and antagonism between, populations. A combination of high-throughput interaction screening, molecular genetics, and genomics revealed that antibiotics are produced by only a few members of each population, while all other members are resistant. In the past, lack of knowledge of the ecological structure of microbial populations has led to interpretations of antibiotic production and resistance as being largely driven by short-lived, cyclic invasions of populations by antibiotic-producing resistant bacteria. This work shows that structured, socially cohesive bacterial populations exist in the wild and form organizational patterns similar to those of animal and plant populations.

  10. Oncogenic TACC-tics

    Human cancers exhibit many types of genomic rearrangements—including some that juxtapose sequences from two unrelated genes—thereby creating fusion proteins with oncogenic activity. Functional analysis of these fusion genes can provide mechanistic insights into tumorigenesis and potentially lead to effective drugs, as famously illustrated by the BCR-ABL gene in chronic myelogenous leukemia. Singh et al. (p. 1231, published online 26 July) identify and characterize a fusion gene present in 3% of human glioblastomas, a deadly brain cancer. In the resultant fusion protein, the tyrosine kinase region of the fibroblast growth factor receptor (FGFR) is joined to a domain from a transforming acidic coiled-coil (TACC) protein. The TACC-FGFR protein is oncogenic, shows unregulated kinase activity, localizes to the mitotic spindle, and disrupts chromosome segregation. In mice, FGFR inhibitors slowed the growth of tumors driven by the TACC-FGFR gene, suggesting that a subset of glioblastoma patients may benefit from these types of drugs.

  11. Iron Hopping

    Iron oxide minerals shuttle electrons around in a wide range of biogeochemical processes. Katz et al. (p. 1200) used time-resolved x-ray absorption spectroscopy to take a closer look at how this happens. By using photoionized surface dyes to inject electrons into three different solid oxide phases, they found that electrons hop among iron centers at rates that depend more on structure in their immediate vicinity than on the extended ordering of the crystal lattice. These observations bolster the prevailing small polaron model in which charge carriers associate closely with individual metal sites.

  12. Evolving Group Formation

    Grouping behavior in prey species has long been thought to constitute an adaptation against predation; however, it has been difficult to characterize the mechanisms by which predator selection shapes prey movement and grouping behavior. Using an approach that combines the selection imposed by a live predator, the bluegill sunfish, with manipulation of computer-generated “prey,” Ioannou et al. (p. 1212, published online 16 August; see the Perspective by Romey) show that “prey” that behave as a group are more likely to survive that those that move in other ways.

  13. Recycle MAP, Rewind Ste5

    Components of the mitogen-activated protein (MAP) kinase pathway for cell signaling in yeast are reused in related pathways that produce very different biological outcomes. So how does a cell know, for example, whether it should grow or mate? Enter Ste5, the prototypical scaffold protein, which binds the set of components from the mating pathway, presumably to sequester them so they can be activated specifically. But Zalatan et al. (p. 1218, published online 9 August; see the Perspective by Davis) found something rather different. Ste5 is not just an inert support structure; it apparently has an active role in the regulatory pathway as an allosteric inhibitor of the MAP kinase, Fus3. It only unclamps Fus3 function when a signal unique to the mating pathway brings Ste5 to the cell membrane.

  14. Relegated to Accessory

    Critical aspects of meiosis, the specialized cell division that makes haploid gametes and spores, evolved from those of the normal mitotic cell cycle. In mitosis, the RecA homolog Rad51 is required for the homology-mediated repair of DNA double-strand breaks (DSBs). DSBs play a critical role in chromosome segregation in meiosis. Cloud et al. (p. 1222) show that the strand-exchange activity of Rad51 is not required in meiosis. Rather, a second meiosis-specific RecA homolog, Dmc1, carries out the homology search and strand-exchange function that Rad51 performs in mitosis, with Rad51 relegated to enhancing the strand-exchange activity of Dmc1. It appears after the gene duplication event that created Dmc1 from an ancestral Rad51. Rad51 took on an accessory role to Dmc1 in meiosis.

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