Editors' Choice

Science  07 May 2010:
Vol. 328, Issue 5979, pp. 669
  1. Physiology

    Easy to Swallow, Hard to Digest

    1. Lisa D. Chong

    The physical formulation of medications is a nontrivial consideration in how readily gains in biomedical research can be translated into marketable treatments. Many compounds are designed to enter the body through the digestive tract; hence the residence time in the stomach is important, particularly in devising oral dosage regimens of medicines in the form of pills. Laulicht et al. have used an inexpensive and noninvasive high-resolution tracking method to measure the forces and torques experienced by a magnetic pill as it moved through the gastrointestinal tracts of healthy humans and animals (dogs and rats) in fasting or fed states. Translational and angular velocities and accelerations were computed on the basis of position and orientation data collected at 10 Hz. The gastric emptying force, which propelled the pills into the intestine, was exerted largely by circumferentially oriented muscle fibers in the human stomach, and was similar in fed humans and dogs, but not fasting subjects, indicating that the fed state in dogs may be a good preclinical model. Such dynamic information may help companies shape pills that better target the preferred sites of drug absorption in patients.

    Proc. Natl. Acad. Sci. U.S.A. 107, 10.1073/pnas.1002292107 (2010).

  2. Cell Biology

    Keep the Exits Clear

    1. Helen Pickersgill

    Open any cell biology textbook and you will find a transmission electron micrograph of a cross section through a cell nucleus. The dense staining of heterochromatin, which is largely inactive and highly condensed, will be clearly visible as dark patches, often lining the inner surface of the nuclear membrane. However, there will be periodic gaps in these heterochromatic territories at peripheral sites where the nuclear pore complexes (NPCs) are situated. NPCs are macromolecular structures that enable the transit of nucleic acids and proteins across the nuclear envelope. Although the existence of these NPC-associated heterochromatin-free regions has been known for over 50 years, how they are generated and what their function is have remained unknown.

    Krull et al. have discovered a role for the NPC-binding protein Tpr in establishing NPC-associated zones free of heterochromatin. In a cell culture model where heterochromatin condensation and heterochromatin exclusion zones around the NPCs could be induced vigorously, they found that depletion of Tpr resulted in dramatic nuclear reorganization as heterochromatin became evenly spread around the nuclear periphery and NPC-associated exclusion zones were lost. Keeping the NPC portals clear of heterochromatin might facilitate passage of the 1000 molecules that are transported through a single NPC per second in human cells. That a single protein can generate these exclusion zones is somewhat surprising and an important first step.

    EMBO J. 29, 10.1038/emboj.2010.54 (2010).

  3. Chemistry

    Gels by Reduction

    1. Phil Szuromi

    Short linear peptides have a propensity to assemble in solution into β-sheet structures that can form gels. Bowerman and Nilsson describe a strategy for triggering gelation through reduction. They took an amphipathic peptide sequence, (Phe-Lys-Phe-Glu)2, and flanked it with cysteine residues and a glycine at the C terminus. The peptide was released into a water-acetonitrile solution and cyclized at the cysteine sites through disulfide bond formation. When diluted in aqueous solution, this cyclic peptide had no tendency to form secondary structures. However, when exposed to a reductant, such as dithiothreitol or tris(2-carboxyethyl)phosphine, to break the S-S bond, the linear form could produce hydrogels at 10 mM concentrations. Such triggers might be exploited within cells or tissues where changes in reducing conditions can occur.

    J. Am. Chem. Soc. 132, 10.1021/ja1025535 (2010).

  4. Ecology

    Fewer Trips to the Mediterranean

    1. Andrew M. Sugden

    The blackcap (Sylvia atricapilla) is a small passerine bird that breeds in northwestern Europe and winters in southern Europe and Africa; consequently, it has become a favored species for studying the evolutionary genetics of migration. Pulido and Berthold have found a significant reduction in migratory activity (measured as the fraction of locomotory activity that captive nocturnal migrants showed at night) in birds collected in the wild over a 13-year period (1988–2001), and observed a similar reduction in birds raised in captivity. In an artificial selection experiment in which blackcaps were bred for reduced migratory activity over four generations, migratory activity showed significant reductions, and after four generations a small proportion of individuals showed no propensity to migrate at all. Taken together, these results indicate the potential for rapid adaptive reduction in migration behaviors in response to climate change.

    Proc. Natl. Acad. Sci. U.S.A. 107, 7341 (2010).

  5. Chemistry

    The Life and Times of Sunscreen

    1. Nicholas S. Wigginton

    Nanomaterials boast a multitude of current and projected commercial uses that take advantage of their unique and beneficial properties, but the health and environmental risks they present are relatively unknown. Screening and eventual regulation are problematic because even materials of the same chemical composition have such a wide range of morphologies (including size, shape, coating, aggregation state, and crystalline phase variations) that affect their reactivity. In a demonstration of the complexity of such systems, Labille et al. examined the aging of composites of titanium dioxide (TiO2) nanoparticles commonly used in sunscreen and cosmetics. The composites—composed of several nanoparticles surrounded by a thin Al(OH)3 shell and bound in a hydrophobic polymer matrix—dispersed in water over time because of the degradation of the polymer. When aged in the presence of light, the polymer degradation rate increased, possibly due to photocatalysis by TiO2. In either case, once the polymer degraded, the remaining Al(OH)3 shell determined the stability of the composites. Stability was also sensitive to the concentration of natural organic matter; at low levels characteristic of groundwater, the composites aggregated, but higher levels characteristic of surface waters kept the composites suspended. These and similar studies raise the question of whether the nanomaterials studied and characterized in laboratory settings look or behave as they do in the environment.

    Environ. Pollut. 158, 10.1016/j.envpol.2010.02.012 (2010).

  6. Genetics

    Do These Genes Make Me Look Fat?

    1. Laura M. Zahn

    Deciphering the genetic predispositions behind complex traits can be difficult for many reasons, one of which may be variation in the genetic response to the environmental changes. To examine the effects of genes and environment, Reed et al. looked at the phenotypic response of body weight among multiple Drosophila lines in response to different diets (high-fat, low-calorie, high-sugar). They found that the variation in several metabolism-related traits, such as blood sugar and lipid storage levels, was driven more by interactions between the genetics of a line and the diet; not much of the variance could be explained by the differences in diet alone. In response to a high-fat diet, populations of flies showed an increase in the genetic variance, suggesting that there was a loss of robustness in the metabolic traits. These results suggest that in flies, gene-by-diet interactions are widespread and probably influence, perhaps rather strongly, their phenotypes.

    Genetics 185, 10.1534/genetics.109.113571 (2010).

  7. Physics

    Inching Toward Equilibrium

    1. Jelena Stajic

    Ultracold Bose and Fermi gases in optical lattices show promise to simulate quantum phases in condensed-matter systems. The manipulation of atoms in these experiments often involves nonequilibrium processes, such as ramping up the lattice potential; nevertheless, an equilibrium thermodynamics framework is normally used to describe the system, provided that the speed of tunneling between neighboring sites is faster than the ramping rate.

    Now, Hung et al. demonstrate that the equilibration process after a ramp can be surprisingly slow. They load an almost pure, flat Bose-Einstein condensate into a two-dimensional optical lattice and use in situ imaging to monitor the density profile evolution after a ramp for various final lattice depths close to the boundary between the superfluid and Mott insulator regimes. The characteristic time for reaching an equilibrium mass distribution increases with the final lattice depth and is two orders of magnitude higher than the tunneling time scale. A radial temperature gradient also appears. The authors suggest that the sluggish mass and heat flow are a consequence of quantum criticality, as well as the low dimensionality of the system.

    Phys. Rev. Lett. 104, 160403 (2010).