Editors' Choice

Science  19 May 2006:
Vol. 312, Issue 5776, pp. 974

    Resisting Renegade Cells

    1. Stephen J. Simpson

    Despite the many examples involving experimental or clinical stimulation of immune responses to tumor cells, it is not yet clear to what extent the immune system might be able to combat or suppress malignancy on its own. The spontaneous remission/complete resistance (SR/CR) strain of mice is unusual in that it strongly resists challenges with high-dose inoculations of tumor cells that would otherwise be lethal. This resistance segregates as a single-locus dominant trait and correlates with significant leukocyte infiltration of the cancer.

    Building on their earlier findings, Hicks et al. report that the infiltrate contains a variety of leukocyte subsets, including T cells, natural killer (NK) cells, neutrophils, and macrophages. Direct contact and killing of tumor cells by these immune response effectors could be measured in vitro, and resistance to both new and established cancers was conferred on wild-type mice by adoptive transfer of either bone marrow or other leukocyte fractions. Notably, SR/CR resistance was maintained even after depletion of B and T cells, revealing an innate immune component of the phenotype. The tantalizing possibility exists that characterization of this locus will improve our understanding of immune-mediated resistance to malignancy. — SJS

    Proc. Natl. Acad. Sci. U.S.A. 103, 10.1073/pnas.0602382103 (2006).


    Designer Pad

    1. Stella M. Hurtley

    Legionella pneumophila, an opportunistic bacterial pathogen responsible for Legionnaire's disease, reproduces inside specialized vacuoles after phagocytosis by its host cells—either free-living protozoa or human macrophages. Legionella-containing vacuoles do not fuse with other endocytic vesicles but instead recruit vesicles from the early secretory pathway. They modify the vacuole membrane by using a type IV secretion system, which transports effector proteins made by the bacterium into the host cell.

    Weber et al. examined the role of host-derived phosphoinositides (PIs) in intracellular replication and found that they are important in the anchoring of secreted bacterial effector proteins inside the vacuole. Specific effector proteins interact with a variety of host-derived PIs and, in particular, recruit PI(4) phosphate in order to attach themselves to the vacuolar membrane. Mutant bacteria lacking functional type IV secretion systems fail to modulate host cell PI metabolism and are degraded. — SMH

    PLoS Pathog. 2, e46 (2006).


    Twisting MOFs into Ferroelectrics

    1. Phil D. Szuromi

    Ferroelectric materials, in which the bulk lattice exhibits a spontaneous net dipole moment, have numerous applications as memory elements, insulators, and resonators. Typical ferroelectrics are composed of inorganic salts such as BaTiO3 and LiNbO3, but there is interest in finding organic or organometallic alternatives.

    Ye et al. explored the potential for ferroelectricity in a metal-organic framework (MOF) architecture, a porous motif that has been studied for chemical applications such as sorption or catalysis. They found that hydrothermal reaction of CdCl2 and NaN3 with homochiral N-(4-cyanobenzyl)-(S)-proline yields a MOF with the necessary noncentrosymmetric lattice symmetry; x-ray crystallography revealed a slight displacement of the Cd atoms in their octahedral sites. The temperature dependence of the dielectric loss suggests that the Cd-Cl bond vibration or the displacement of the proton on a tetrazoyl group (the adduct of azide-to-nitrile cycloaddition) underlies the relaxation process, and the authors estimate a dielectric constant of ∼40 for this material at ∼220 K. — PDS

    J. Am. Chem. Soc. 128, 10.1021/ja060856p (2006).


    Shaking Up Viscous Fluids

    1. Marc S. Lavine

    The transition from smooth laminar flow to chaotic turbulent flow is a problem of fundamental interest and is also of practical relevance in areas ranging from manufacturing to weather pattern formation. In Newtonian fluids such as pure water, the transition arises as a consequence of an increase in the flow rate, which in turn causes bifurcations in the flow that lead to localized flow rolls and then to chaotic or turbulent flows; in viscous fluids, these inertial instabilities are suppressed, but turbulent-like transitions have nonetheless been observed.

    Schiamberg et al. used a parallel plate rheometer to study a series of polymer solutions in which instabilities arise from the elastic motions of individual polymer chains as they stretch and contract within a less viscous solvent. On slowly increasing the flow stress, the authors observed secondary flows: first, axially symmetric rings that formed near the outer edge of the sample; then, with rising shear stress, competing nonsymmetric rings that led to chaotic multispirals and eventually to elastic turbulence, with an accompanying factor of 13 rise in the apparent viscosity (or resistance to flow). Changing the polymer concentration induced additional flow modes, offering a rich library for theoretical development and comparison with the inertial transitions seen in Newtonian fluids. — MSL

    J. Fluid Mech. 554, 191 (2006).


    Ice Fishing

    1. Gilbert J. Chin

    Double-stranded DNA is a wonderfully stable repository of information, as can readily be seen in the macroscopic threads of salmon sperm DNA. Compacting and condensing it into higher-order structures such as chromatin and chromosomes protects that information and allows it to fit into the nucleus. Gene expression, however, demands access to unwrapped and unwound DNA strands, which opens the door to unplanned and unwanted double-stranded breaks. These moments of vulnerability touch on a currently debated issue: the relative spatiotemporal distributions of chromosomes, with respect to each other and to transcriptionally active nuclear regions.

    Branco and Pombo have adapted fluorescence in situ hybridization for use on ultrathin cryosections and examined how much of each chromosome territory mixes with that of the others (roughly 40% on average). They go on to show that activating expression (by applying interferon-γ to lung fibroblasts) from the MHC class II locus on chromosome 6 increases the penetration of this region into the territories of other chromosomes. Finally, the intriguing correlation between the amount of intermingling in human lymphocytes, calculated for pairs of chromosomes, and previous measurements of translocation frequencies in the same cell type highlights the importance of happenstance in rearrangements. — GJC

    PLoS Biol. 4, e138 (2006).


    Bend Origins

    1. Jake Yeston

    Chemical paradigms for multiple bonding were recently challenged by the synthesis of a chromium dimer that appeared to be held together by the interaction of 10 electrons between the Cr centers (see Nguyen et al., Reports, 4 November 2005 p. 844). Before this discovery, isolable compounds were limited to bonding motifs in which eight or fewer electrons were shared between any two atoms. Orbital conformations in a quintuple bonding framework were largely expected to induce a linear geometry, but the bulky triaryl ligands capping the Cr centers adopted a bent, mutually trans configuration.

    Brynda et al. have analyzed this geometrical conundrum using high-level quantum-mechanical calculations incorporating multiconfigurational perturbation theory. For a model compound with phenyl groups in place of the triaryl ligands, the linear conformer was energetically favored over the bent form by only 1 kcal/mol. Orbital occupancy analyses were consistent with participation of all 10 electrons in both conformers, though with repulsive antibonding contributions lowering effective bond orders to 3.69 and 3.52 for the linear and bent forms, respectively. — JSY

    Angew. Chem. Int. Ed. 45, 10.1002/anie.200600110 (2006).

  7. STKE

    PTEN Affects Brain Development

    1. Elizabeth M. Adler

    Mutations in the tumor suppressor PTEN (phosphatase and tensin homolog on chromosome ten) are associated not only with tumor development but also with several brain disorders. Intriguingly, PTEN mutations have been reported in individuals with autism spectrum disorders (ASD) occurring in conjunction with macrocephaly. Kwon et al. used mutant mice in which Pten was deleted in a subset of differentiated neurons in the hippocampus and cerebral cortex to investigate the effects of PTEN on brain development and behavior. The mutant mice exhibited behavior evocative of that of individuals with ASD: atypical social interactions, exaggerated responses to stressful sensory stimuli, and atypical responses in paradigms designed to assess anxiety and learning. Their brains were enlarged in the regions in which Pten was deleted; this was associated with hypertrophy of the cell bodies of Pten-negative neurons as well as increased and abnormal growth of neuronal processes. The hypertrophied neurons showed increased phosphorylation of downstream targets of Akt signaling. Thus, abnormal activation of Akt signaling in a subset of neurons appears to promote macrocephaly and behaviors that resemble some of those associated with ASD. — EMA

    Neuron 50, 377 (2006).

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