Editors' Choice

Science  19 Nov 2004:
Vol. 306, Issue 5700, pp. 1261

    Catenane Closure via Chloride

    The assembly of interlocking molecular rings, or catenanes, normally relies on some sort of templating mechanism to hold the components together while chemical reactions complete the cyclization. Sambrook et al. report on the use of anions as templating agents. They use a catenane precursor and a macrocyclic ring, each of which bears a cleft region that brings two amide groups into close proximity. Binding of a single chloride ion by these four amides holds the precursor onto the macrocyclic ring; this interaction is also stabilized by π-π stacking interactions between hydroquinone groups on both molecules. Ring-closing metathesis cyclizes the precursor, either as a monomer to form two interlocked rings or as a dimer to form a [3]catenane. The [2]catenane product selectively binds chloride anions over acetate and dihydrogen phosphate. — PDS

    J. Am. Chem. Soc. 10.1021/ja045080b (2004).


    Restricting Morphogens

    During embryonic development, gradients of morphogens and signaling molecules help to define how development proceeds. Scholpp and Brand examined how the gradient of a member of the fibroblast growth factor family, Fgf8, is generated and maintained in the nascent neuroectoderm of living zebrafish embryos. By looking at fluorescently tagged Fgf8 as it spread from its site of origin through target tissue, the authors obtained evidence for a restrictive clearance mechanism in which the factor is cleared from the immediate environment around target cells by endocytosis and subsequent degradation. When endocytosis was blocked, Fgf8 accumulated extracellularly and activated gene expression in more distant target cells, whereas activating endocytosis had the opposite affect, restricting the effective range of Fgf8.

    Belenkaya et al. looked at the movement of another growth factor-related morphogen, Drosophila Decapentaplegic (Dpp), during anteroposterior patterning of the wing. In this system, movement of the growth factor was restricted by binding to extracellular proteoglycans rather than by endocytosis, leading again to a gradient of morphogen response. — SMH

    Curr. Biol. 14, 1834 (2004); Cell 119, 231 (2004).


    The Cost of Escape

    Cytotoxic CD8 T cells (CTLs) begin their assault on the HIV pathogen soon after infection occurs, and the efficiency with which they achieve early control is a deciding factor in the course infection takes. Conversely, the virus defends itself by mutating the epitopes targeted by the CTLs in an attempt to escape recognition. Jones et al. explored which characteristics of early CTL responses to HIV corresponded with the subsequent ability to control the viral load.

    In an individual showing good viral control, the number and breadth of epitopes recognized by CTLs were relatively large, in contrast to the strong focus of CTLs on a handful of immuno-dominant epitopes in two individuals exhibiting poor viral control. In these two people, new viruses with numerous CTL epitope mutations appeared soon after infection, suggesting that early selective pressure from CTLs had been countered successfully by the virus. On the other hand, the individual with good viral control carried viruses with far fewer mutations, consistent with the relatively slow emergence of new escape mutants in the months after the acute phase of infection. Early control thus appears to be determined by broad recognition of multiple viral epitopes, increasing both the opportunity for viral detection by CTLs and the potential cost of escape mutations to intrinsic viral fitness. — SJS

    J. Exp. Med., 200, 1243 (2004).


    Unraveling the Knitted Sleeve

    The surroundings in which membrane proteins reside consist of a hydrophobic interior (the fatty acid tails of phospholipids), a polar interfacial zone (the phospholipid head groups), and the aqueous compartments on either side of the bilayer. Rather than analyzing the energetics and dynamics of membrane protein insertion in the midst of such heterogeneity, Ganchev et al. have resorted to extracting peptides in a model membrane system. A shorter peptide and a longer one, both of which were previously shown to adopt a single-span α-helical conformation in membranes, and two phospholipids, one gel-like and one fluid, were mixed and probed by atomic force microscopy. Pulling (at a range of speeds) resulted in extraction of the peptide, at forces of about 90 pN applied to the gel-like mixture and only 60 pN for the more fluid membrane. A closer look at the resistance to extraction suggests that it arises primarily from the energy required for unwinding the first turn of the helix and dragging these residues from the hydrophobic interior into the interfacial region. — GJC

    Biochemistry 10.1021/bi048372y (2004).


    A Brighter Future by Working Together

    Both metal nanoparticles and semiconducting nanowires have interesting optical and electrical properties, but what happens when they are coupled together? Lee et al. try to answer this question for a collection of CdTe nanowires that are complexed with Au nanoparticles using the biotin-streptavidin ligand-receptor pair to connect the two together.

    When these components were mixed in solution, the authors observed a fivefold increase in the peak luminescence intensity and a blue shift of the spectra that developed gradually with time. Surprisingly, as the intensity increased, the photoluminescence lifetime decreased, which is in contrast to normally observed trends. The authors interpreted their observations within a model in which the Au nanoparticles form a coaxial shell around the nanowires. They find that the gold particles generate an electro-magnetic field that stimulates photon emission from the nanowires, in a process that is reminiscent of surface-enhanced Raman scattering. This effect is not due to individual nanoparticle-nanowire interactions but instead to the collective effect of the aggregated metallic nanoparticles. — MSL

    Nano Lett. 10.1021/nl048669h (2004).


    Residence Time

    Agricultural and industrial activity has increased the amount of N added to rivers far above natural levels. This N, added mostly as nitrate, is a major pollutant that contributes to eutrophication and produces anoxia in water bodies of all sizes; it also is a source of the greenhouse gas nitrous oxide (N2O). The magnitude of the impact of riverine N is hard to judge, however, because of large gaps in our knowledge about its removal during transport through the river system.

    Donner et al. use an aquatic transport model to investigate in-stream N removal and N2O emissions in the Mississippi River system and how they may be affected by interannual climate variability. Their results show that the fraction of N removed in the river system can vary by nearly a factor of 2, with a threefold range in the associated N2O emissions, depending on precipitation. The lowest fraction of N removal and the greatest N2O emissions occur in the wettest years, when river flow is greatest and the residence time of the water in the rivers is shortest. — HJS

    Geophys. Res. Lett. 31, L20509 (2004).

  7. STKE

    Calcium Signals from the Mitochondria

    Xu et al. used human cell lines that expressed inducible nitric oxide synthase under the control of regulated promoters to investigate the effects of inhibiting mitochondrial respiration with nitric oxide (NO). NO, acting independently of soluble guanylate kinase activity, stimulated expression of glucose-regulated protein 78 (Grp78), an endoplasmic reticulum (ER)-resident chaperone protein whose expression is enhanced as part of the ER stress response. NO produced an increase in the amount of the soluble transcription factor p50 ATF6, which is generated through a calcium-dependent process involving regulated intramembrane proteolysis. NO-dependent stimulation of p50 ATF6 production and of Grp78 expression was attenuated in cells depleted of intracellular calcium, and both an intracellular calcium chelator and cyclosporin A (which interferes with mitochondrial calcium signaling) reduced NO-dependent ATF6 cleavage and prevented the NO-dependent increase in Grp78. Thus, the authors propose that NO-dependent inhibition of mitochondrial respiration affects calcium signaling between the mitochondria and the ER, thereby stimulating production of p50 ATF6 and the expression of genes involved in the ER stress response. — EMA

    Nature Cell Biol. 6, 1129 (2004).

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