This Week in Science

Science  10 Oct 1997:
Vol. 278, Issue 5336, pp. 197
  1. Recognized by their caps

    T cells recognize proteins and peptides through major histocompatibility complex (MHC) proteins, which bind peptides and “present” them to antigen receptors on T cells. However, T cells see more than just peptides—they can be activated by binding to certain lipids and glycolipids, which are presented by proteins that are distant cousins of those encoded in the MHC region. Moody et al. (p. 283) identified a glycolipid antigen from mycobacteria and did a detailed analysis of which parts of the glycolipid were critical for recognition. Recognition depended mainly on hydrophilic cap of the glycolipids; naturally occurring substitutions of the hydrophobic tail were well tolerated. This result is consistent with the recently solved structure of CD1—both sets of work support the concept that the deep CD1 binding groove is designed to accept a hydrophobic tail, which allows the carbohydrate cap to stick out and become a target for T cells.

  2. Faster together

    Diffusion of atoms and molecules on surfaces is important for catalytic processes. Although strongly bound systems, such as metals on metal surfaces, have been investigated for some time, the study of weakly bound systems, such as carbon monoxide on metals, has been more difficult, as measurement can more easily affect the molecular motion. Briner et al. (p. 257) performed scanning tunneling microscopy of carbon monoxide on copper surfaces and found that dimers and longer chains move faster, through single molecule jumps, than monomers; this difference is attributed to a reduction of vibrational entropy in the chains rather than to a difference in activation energy.

  3. Pore alignment

    Mesoporous materials, with typical pore sizes of a few nanometers, are complementary to zeolites, which have smaller pores and thus can only take up molecules up to a certain size. However, large-scale applications of mesoporous materials often require alignment of the pores over macroscopic length scales, which has been difficult to achieve. Tolbert et al. (p. 264) have devised a strategy whereby the precursor material, a liquid crystal, is aligned in a magnetic field; the alignment is preserved during the processing stages, resulting in a material with macroscopically aligned mesopores.

  4. Io-Jupiter feedback

    Io, the most volcanically active body known in the solar system and Jupiter's nearest large satellite, is intimately coupled to Jupiter's magnetosphere. Brown and Bouchez (p. 268; see the Perspective by McGrath, p. 237) observed sulfur ions (S+) in the Io plasma torus and sodium atoms in the neutral plasma cloud associated with the jovian magnetosphere for 6 months. During this time, a volcanic eruption on Io created a large plume that increased the Na content of the neutral cloud, followed by a delayed increase in the S+ content of the Io torus. These excess S+ ions dissipated nonlinearly, which suggests that the jovian magnetosphere stabilizes itself with a nonlinear feedback mechanism against the sporadic volcanic outbursts of Io.

  5. Trapped organics on Ganymede and Callisto

    Jupiter's largest satellites, Ganymede and Callisto, show evidence for water ice on their surfaces that may have been trapped early in the evolution of our solar system. McCord et al. (p. 271), using near-infrared spectra from the Galileo orbiter, found evidence for CO2, SO2, and some organics trapped within the water ice and hydrated minerals on the surfaces. Such components could be derived from a variety of sources, including interstellar ices, the jovian magnetosphere, and meteorites. Fitting the spectra with these sources will help define how and where carbon, hydrogen, and oxygen were distributed in the early solar system.

  6. Pain relief

    Prolonged pain can be extremely debilitating, but sensitivity to painful stimuli is critical for the avoidance of serious injury. Two reports look at the mechanisms that generate acute pain but that allow the avoidance of long-term pain, or extreme sensitivity, to what should be nonpainful stimuli (see the Perspective by Iadarola, p. 239). When noxious stimuli are applied, a peptide, known as substance P (SP), is released and binds to neurons possessing the SP receptor. The role of these neurons in acute and chronic pain perception has been unclear; Mantyh et al. (p 275) now show that these neurons can be specifically removed by applying SP coupled to a toxin. The removal of these neurons did not change the animals' responses to acute pain but made them far less sensitive to chronic pain. Peripheral nerve injury can cause an increased sensitivity to pain (neuropathic pain). Malmberg et al. (p. 279) found that this pain state requires the expression of a brain-specific form of protein kinase C (PKCγ). Mice genetically engineered to lack the PKCγ protein had a normal sensitivity to acute pain but were almost totally lacking in neuropathic pain after injury.

  7. Viral infection and angiogenesis

    Continued analysis of proteins encoded by the Kaposi's sarcoma virus HHV-8 are providing insights into pathogenesis and potential as therapeutic agents against HIV. Boshoff et al. (p. 290) found that two viral chemokine-like proteins, vMIP-I and -II, promoted the formation of blood vessels, which may be important in the development of Kaposi's sarcoma. The vMIP-II can activate and attract certain white blood cells (eosinophils), primarily through the CCR3 receptor. HIV infection through this receptor is also the most sensitive to inhibition by vMIP-II.

  8. Unraveling actin during cell death

    When a cell gets a signal to initiate the programmed cell death cascade, a series of proteases called caspases are activated by cleavage of one another. Other proteins can also serve as substrates for caspase cleavage, and Kothakota et al. (p. 294) show that gelsolin, a protein that severs actin chains in a calcium-dependent fashion, is cut during apoptosis. This cleavage liberates an activated gelsolin fragment that depolymerizes actin into monomers in an unregulated fashion and which is responsible for the morphologic changes associated with apoptosis. Cells that had no gelsolin had delayed apoptosis and only limited morphologic changes. Thus, gelsolin seems to potentiate the cell death process, a role consistent with its recently noted down-regulation in many human tumors.

  9. Prion diseases

    Certain human brain disorders—notably Creutzfeldt-Jakob disease—are caused by prions, accumulations of posttranslationally modified proteins that can be infectious. “Mad cow” disease (or bovine spongioform encephalopathy) is also a prion disease, and it has been suggested that a new variant of Creutzfeldt-Jakob disease arose from transfer of the bovine disease to humans. Prusiner reviews the evidence from experimental analysis of prion diseases that pertains to this putative transfer.

  10. Completing the circuit

    Measurements of charge transport in single organic molecules and their conductance are experimentally very challenging. Reed et al. adsorbed organic molecules onto a mechanically controllable break junction formed by atomically sharp gold electrodes. The current-voltage and conductance measurements indicate that, under appropriate conditions, the conductance of a single molecule can be measured in this way. The technique should be applicable to a wide range of compounds and conditions.

  11. Deep connections

    Near the island of Fiji in the southwest Pacific Ocean, the Pacific plate is being subducted beneath the Australian plate. This subduction has created the most active and uniform seismic zone that extends throughout the upper mantle. Zhao et al. used this seismicity, the recent deployment of additional seismometers, and an ocean bottom seismic experiment to image the three-dimensional velocity structure of the crust and upper mantle. They found slow velocity anomalies from the back-arc volcanism at the surface associated with slow anomalies at depths greater than 100 kilometers in the upper mantle. These results indicate a direct connection between dehydration and melting of the deeply subducted crust with the shallow volcanism behind the subduction zone.

  12. Early intermediates

    The initial steps of the activation of the strong carbon-hydrogen bonds of alkanes by metal complexes in solution have been studied spectroscopically. Bromberg et al. used the complex Tp*Rh(CO)2 [Tp*, HB(3,5-dimethylpyrazolyl)3], which has a sufficiently high photochemical yield to be studied with ultrafast spectroscopy. Intermediates along the pathway were identified, and from their lifetimes the energy barrier for their formation could be estimated. [See the cover.]

  13. What makes a HIT

    Many proteins are members of the histidine triad family (which contain the His-x-His-x-His motif, where x is any amino acid), but it has been difficult to associate specific biological activity with them. In an effort to better understand the catalytic properties of these proteins, Lima et al. analyzed crystal structures that they have determined for two members of this enzyme family, fragile histidine triad protein (FHIT) and protein kinase C interacting protein, in their unliganded forms as well as bound to substrate analogs, transition state analogs, and the nucleotide product (adenosine monophosphate). These studies indicate that the HIT proteins are nucleotidyl hydrolases, transferases, or both.

  14. Edited antibodies

    During development, the RAG genes of B cells must rearrange the multiple components of their immunoglobulin genes (the product of which is an antibody) so that each B cell eventually expresses a unique antibody. When B cells are exposed to antigen, their specificity seems to evolve, through a process called somatic mutation, to produce antibodies that have greater affinities. The RAG genes get re-expressed in the germinal centers, where B cells meet antigen and hypermutation takes place. However, past work has shown that expression of the RAG genes does not always correlate with activity. Papavasiliou et al., working with a transgenic system, and Han et al., working with normal mice, now show that the reexpressed RAG genes induce renewed recombination of the immunoglobulin genes to produce “edited” antibodies. [See the Perspective by Liu.]

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