This Week in Science

Science  03 Oct 1997:
Vol. 278, Issue 5335, pp. 9
  1. Winter ozone hole

    The processes leading to the Antarctic ozone hole have been studied intensively, but because of technical difficulties in performing measurements during the polar winter, when little sunlight reaches the Antarctic, most measurements are constrained to latitudes below 75° throughout winter. Roscoe et al. (p. 93) present total ozone measurements at Faraday at 65°S throughout the winters of 1990, 1991, and 1994, and show that ozone depletion starts in June. Model calculations indicate that this is not an isolated phenomenon and that ozone destruction starts at the edge of the sunlit vortex in midwinter.

  2. From defects to devices

    Defects along carbon single-wall nanotubes (SWNTs) can produce abrupt changes in their local electrical characteristics. Collins et al. (p. 100; see the Perspective by Saito, p. 77) extracted SWNTs from bundles, or “ropes,” of tubes (for distances up to 2 micrometers) with a scanning tunnel microscope tip, which adhered strongly to the end of the tube. As the tube was extracted, the conductivity could abruptly change upon slight movement (a few nanometers) from a response typical of graphite to one that was highly nonlinear and rectifying. Such abrupt “on-off” character could potentially be used in devices.

  3. Extra deliveries

    Rocks from the Lower Ordovician (dating from about 480 million years ago) found in Sweden contain abundant small meteorites compared with older and younger rocks. Schmitz et al. (p. 88) collected additional meteorite samples from these rocks and show using osmium isotopes and iridium concentrations that the influx of cosmic matter to the Earth increased at this time by about an order of magnitude. They speculate that the increased dust may be related to other evidence of a major impact or disruption of a meteorite parent body at this time.

  4. Designer protein

    A computational algorithm based on physical chemical potential functions and stereochemical constraints has been used to screen a large library of possible amino acid sequences against a design target. Dahiyat and Mayo (p. 82; see the Perspective by DeGrado, p. 80) screened 1.9 × 1027 combinations to obtain full sequence design 1 (FSD-1), a 28-residue protein that was designed to adopt a ββα motif of a zinc finger domain. The solution structure indicates that the protein adopts the targeted fold.

  5. Actively unresponsive

    Under the wrong circumstances, T cells can be turned off, instead of on, by the antigen for which they are specific. Boussiotis et al. (p. 124) found that the resultant state of unresponsiveness, called anergy, is maintained by the presence of an activated small G protein, Rap1. Thus, the inability to respond to antigen is not only due to a break in the signaling pathway that culminates in the production of the cytokine interleukin-2, but to the active turning on of an alternative pathway.

  6. Weighty factor

    Body weight can be regulated by interactions of neuropeptides and their receptors. Agouti peptide, normally expressed in the skin where it regulates pigmentation, can cause obesity when overexpressed in mice. Agouti-related peptide (AGRP) shares some sequence similarity with Agouti, but, as shown by Ollmann et al. (p. 135), differs in expression and signaling properties. AGRP, normally expressed in the adrenal glands and the hypothalamus, binds a specific subset of the receptors available to Agouti. Overexpression of AGRP in mice affects body weight but not pigmentation.

  7. CAML with two humps

    The CAML protein (calcium-signal modulating cyclophilin ligand) was originally identified as interacting with cyclophilin B and thus thought to participate in the cellular actions of the immunosuppressant cyclosporin A and regulation of the transcription factor NF-AT in lymphocytes. Von Bülow and Bram (p. 138) have now identified another protein, called transmembrane activator and CAML-interactor, or TACI, that interacts with CAML. TACI is a member of the tumor necrosis factor receptor superfamily, and cross-linking of TACI with antibodies leads to activation of NF-AT and other transcription factors. Their results suggest the existence of unusual signaling mechanism in which interaction of the cell surface receptor TACI with CAML, which is found on intracellular vesicles, appears to be required for activation of NF-AT in response to TACI.

  8. Heat shock proteins versus cancer

    One of the most intractable problems in cancer treatment today is metastasis. Tamura et al. (p. 117) examined nonimmunogenic tumors of various histologic origins in a mouse model of metastatic cancer. They isolated the heat shock protein GP96, bound to random peptides from its cellular milieu, from either the primary tumor or a metastatic variant and injected it into mice that had well-established tumors. Primary tumors as well as metastases regressed, and lifespan was extended.

  9. Tuning channels

    Cyclic nucleotide-gated ion channels in olfactory and retinal receptor cells are involved in the response to sensory stimuli. Varnum and Zagotta (p. 110) show that the amino-terminal domain of the channel, which does not bind to the ligand but to the calcium sensor calmodulin, plays a direct role in “tuning” the channel-gating properties after ligand binding in response to intracellular calcium levels.

  10. Oligomeric signal

    The response of yeast to mating pheromone occurs through a complicated signaling pathway that has similarity to signaling pathways in vertebrates. Binding of the pheromone to its receptor activates a heterotrimeric guanine nucleotide-binding protein (G protein). The β subunit of the G protein apparently “talks” to a protein, Ste5, which serves as a scaffold for a series of protein kinases that propagate the signal. Inouye et al. (p. 103) show that oligomerization of Ste5 is necessary and sufficient for signaling. They define a protein domain within Ste5 that is required for interaction with the G protein and for dimerization. Similar domains occur in other proteins including BRCA1, the human breast cancer susceptibility-determining protein.

  11. Cometary origins

    Chemical analysis, and particularly isotopic analysis, of comets is key for inferring their origin, composition, and evolution. (Jewitt et al. report measurements of carbon, nitrogen, and sulfur isotopes in Comet Hale-Bopp. The isotopic values are consistent with solar values, and thus the cometary volatiles likely have an origin within our solar system.

  12. Reading with fewer errors

    Holographic recording has the potential for storing vast amounts of data, but a significant challenge has been the accurately retrieval of information in a digital format that can be readily manipulated. (Shen et al. make use of time-domain holography, in which the signals representing data are separated in time from the writing and reading pulses. They also demonstrate an algorithm for retrieving data that lowers the error rate sufficiently so that error-correcting codes can be avoided. Although such systems still require the use of rare-earth doped crystals at cryogenic temperatures, the optical storage method developed should be compatible with improved data-storage media.

  13. Toward self-avoidance

    Antigen presentation to the right T cells will initiate an immune response, but there are times when the wrong (self) peptides may be bound to the class II molecules, and an autoimmune response could develop. How is peptide loading controlled? (Denzin et al. find that the system that helps load peptides onto class II molecules, coordinated by a class II like molecule called DM, is itself regulated by another class II-like molecule, DO. DO binds to DM and makes it much less efficient at loading peptides onto class II. During an infection, cells that normally do not express class II or DM respond to interferon- γ by turning on those genes and the cells become as good as “professional” antigen presenting cells (APCs), like macrophages, at presenting antigen and turning on T cells. Professional APCs, however, always express DO, which could conceivably be normally functioning to put a damper on expression of self peptides (and inadvertent activation of autoimmunity). During an infection, activated professional APCs would increase the ratio of DM to DO and thereby overcome the block on presentation.

  14. Death without calcium

    The death of neurons during brain development and in some diseases can be prevented by the elevation of potassium concentrations outside the cell. This effect has been assumed to be mediated indirectly, by potassium's effect on calcium, which is well-known to cause apoptosis. Now (Yu et al. show that in certain types of neuronal apoptosis enhancement of the delayed rectifier postassium current and subsequent loss of intracellular potassium may be a necessary and sufficient step for cell death.

  15. Controlled tumorigenesis

    To learn more about the role of tumor suppressor genes in human cancer, scientists often create mouse models in which one or both alleles of the genes are inactivated. In many cases, however, the mutant mice die prenatally because the missing gene has a critical role in embryogenesis. (Shibata et al. have directed inactivation of a tumor suppressor gene to the tissue of interest. They modified the APC gene, which is involved in colon cancer development, so that it contained intra-intronic recognition sites for the Cre recombinase, and then introduced the mutant allele into the mouse germline. Mice homozygous for this modified APC allele developed normally, but upon local infection with an adenovirus encoding the Cre recombinase, they rapidly developed colorectal tumors.

  16. Cleaning house

    The fidelity of the process whereby DNA sequence is converted into proteins is critical for the survival of living organisms. (Taddei et al. have found that the product of the mutT gene in Escherichia coli contributes to the “sanitation” process by removing a potential mutagen, 8-oxo-deoxyguanosine triphosphate, from the ribonucleotide precursor pool that will be used to form RNA. [See the Perspective by (Bridges.]

  17. Firing range

    The predominant inhibitory neurotransmitter in the cortex is γ-aminobutyric acid (GABA), with two major receptor subtypes A and B. (Kim et al. used pairwise recording from thalamic neurons to examine the firing pattern-dependent inhibitory responses. At low, steady firing rates, only small amplitude GABAA responses are present; high-frequency bursts yield large amplitude GABAA responses; and prolonged high-frequency firing recruits GABAB inhibitory potentials. Further, a single neuron can display all three behaviors, and the three firing regimes correlate with network patterns of activity during sleep-wake states.

  18. Mediating export of nuclear proteins

    Several proteins, including those of the karyopherin β family of proteins are involved in the pathway for the import of proteins into the nucleus. Proteins mediating export have been more elusive. (Ossareh-Nazari et al. show that chromosome maintenance region 1 (CRM1), a protein that has sequence similarities to the karyopherin β family, plays a role in signal-mediated protein export from the nucleus. CRM1 forms a complex with the leucine-rich nuclear export signal (NES), and this interaction could be blocked by the drug leptomycin B. A semipermeabilized cell assay showed that leptomycin B could block the export of NES-containing proteins from the nucleus.

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