This Week in Science

Science  11 Jul 1997:
Vol. 277, Issue 5323, pp. 157
  1. Cholesterol traffic tie-up

    Niemann-Pick C disease (NP-C) is a rare inherited disorder that, at the cellular level, is characterized by an inability to mobilize cholesterol. Patients with NP-C develop neurologic abnormalities including ataxia, seizures, and loss of speech, and typically die as children. Carstea et al. (p. 228) (see the news story by Pennisi, p. 180) have identified the human gene responsible for NP-C, and, in parallel work, Loftus et al. (p. 232) show that the same gene is defective in two independent mouse models of the disease. The predicted NPC1 protein has more than 10 putative transmembrane domains and has sequences in common with other proteins involved in cholesterol metabolism. The NPC1 sequence suggests that it participates in cholesterol trafficking from lysosomes to other cellular membranes.

  2. Deciphering additional clues

    The writing system known as epi-Olmec has provided researchers in Mesoamerican studies a number of important and controversial puzzles. In 1993, Justeson and Kaufman published their decipherment of epi-Olmec texts on a stone monument from La Mojarra, Mexico. Now these authors (p. 207) have uncovered an additional text on the same monument that expands the available corpus of epi-Olmec writing and confirms various aspects of the original decipherment.

  3. Orbit and climate

    Variations in the amount and distribution of solar energy arising from cyclic changes in the precession, obliquity, and eccentricity of Earth's orbit are thought to drive glacial climate cycles. One open question has been the origin of the major 100,000-year glacial cycles that developed about 1 million years ago—the forcing by variations in Earth's eccentricity is weak. Muller and MacDonald (p. 215; see the news story by Kerr, p. 183), in an analysis of several ocean climate records, show that before about 1 million years ago, the spectrum of the obliquity cycles closely matched those of the major climate cycles. However, variations in the inclination of Earth's orbital plane can better account for the spectral shape of the 100,000-year cycle.

  4. Magnetic origins

    The magnetic properties of alloys and thin layered materials, such as direction of easy magnetization, can result from complex interactions between components, and the individual contributions can be difficult to resolve. Dürr et al. (p. 213) have used transverse magnetic circular x-ray dichroism to resolve the magnetic contributions of cobalt and nickel layers in a thin film structure by using the different x-ray absorption edges for each element. The much thinner cobalt overlayer changed the easy magnetization direction of the entire film.

  5. Out of sight but not out of mind

    How do we know where things are when we are not looking at them, as when the lights go out in a room? Graziano et al. (p. 239; see the Perspective by Rizzolatti et al., p. 190) have located neurons in the monkey premotor cortex—an area known to be involved in integration of sensory and motor function—that register the presence of an object seen when the lights are on and that continue to maintain their activity after the lights have been turned off. Only after the lights are turned on again and the monkey sees that the object actually had been removed silently under the cover of darkness do the neurons cease responding. Thus, these neurons can code for “object permanence,” an aspect of spatial perception developed by Piaget.

  6. Making lignin the hard way

    The production of paper and pulp from trees requires the removal of lignin, which stabilizes the cell walls of woody plants. Ralph et al. (p. 235) show that although loblolly pine trees carrying a naturally occurring mutation are deficient in an enzyme thought to be critical for lignin biosynthesis, the mutant trees get around the problem by co-opting an unusual subunit to synthesize lignin. Efforts to genetically engineer plants with lower amounts of lignin may be complicated by the apparent flexibility of these metabolic pathways.

  7. Capillary creation

    The tiny capillaries that carry blood throughout our tissues develop first as outgrowths of endothelial cells from larger vessels. Lindahl et al. (p. 242) found that the next step, recruitment of pericyte cells to the capillaries, is dependent on platelet-derived growth factor (PDGF) signaling and is ultimately critical to the structural stability of the capillaries. In mice lacking PDGF-B, the capillaries lack pericytes, and innumerable microaneurysms form when the fetal blood pressure rises near the time of birth.

  8. Simulates stress

    In unstressed cells, heat shock factors (HSFs) are present as inactive monomers in the cytoplasm. Upon heat shock treatment, the factors multimerize, translocate to the nucleus, and activate gene transcription. Kanei-Ishii et al. (p. 246) show that, in the absence of cellular stress, an HSF can be converted to an active form. HSF3 can associate directly with the proto-oncogene product c-Myb in unstressed cells. This complex stimulates translocation of HSF3 to the nucleus for subsequent gene activation. The association of HSF3 and c-Myb may provide a link between the stress response and proliferation control.

  9. Manages without cAMP

    During Dictyostelium development, cyclic adenosine monophosphate (cAMP) is used as a signal both outside and inside the cell. Extracellular cAMP triggers a signaling pathway that activates adenylyl cyclase, an enzyme involved in the production of cAMP. Previous work suggested that extracellular cAMP is crucial for Dictyostelium tissue formation, morphogenesis, and terminal differentiation. Wang and Kuspa (p. 251; see the news story by Gura, p. 181) have demonstrated that when protein kinase A is expressed in cells in which all extracellular and intracellular cAMP were absent, normal Dictyostelium development was observed. Extracellular cAMP was not found to be essential for Dictyostelium development, and all intracellular cAMP signaling was mediated through protein kinase A.

  10. Giving parents to every child

    Between Mars and Jupiter lies a band of objects called the main belt that is assumed to be a major source of near-Earth asteroids and meteorites. Gladman et al. performed numerical integrations in which they injected fragments from collisional disruptions of asteroid parent bodies into main belt resonance bands to determine the dynamic lifetimes of such objects. They found that objects orbit in the main belt for a short period of time before they are pushed into sun-grazing or Jupiter-grazing orbits and then destroyed. These results imply that the probable parent bodies of the observed asteroid families were broken up recently (<<100 million years ago) and thus their “children,” the objects found in the main belt, are very young. Alternatively, asteroids may have been emplaced in nearly Mars-crossing orbits and then slowly moved into resonance orbits in the main belt, which would allow the children to be older and the dynamics of the solar system to be a little quieter.

  11. Critical overlaps

    Structural studies of modified forms of the enzyme isocitrate dehydrogenase (IDH) have revealed insight into the role of precise alignment of the substrate in catalysis. Mesecar et al. modified two cofactors; they changed the adenine of nicotinamide adenide dinucleotide phosphate to hypoxanthine (converting an amino group to a hydroxyl) and changing the magnesium ion, which can coodinate six ligands, to calcium, which can coordinate eight. Crystallographic studies of cryogenically trapped intermediates show that these changes, which cause large decreases in reaction velocity, make only small changes in the orientation of the substrate. These results illustrate the important role of orbital overlap in catalyzing these reactions.

  12. Sulfur and Earth's outer core

    The outer core of Earth consists mainly of molten iron, but some percentage of a lighter alloying element must be present because measurements of the compressional sound waves that travel through the outer core do not fit with experimental determinations or related extrapolations of the properties of molten iron. Several candidates exist for the lighter element, including sulfur, nickel, oxygen, and hydrogen, but there is no clear way to distinguish between these elements. Nasch et al. have added another clue to the composition puzzle. While conducting ultrasonic interferometry measurements of the sound velocity of an Fe-Ni-S liquid, they found that the velocity of this mixture increased with increasing temperature. They attributed this anomalous behavior to sulfur and believe that such behavior could be used to distinguish sulfur from other candidate core components.

  13. Alkane end-games

    Although several routes are now known for activating the normally unreactive alkanes in a controlled manner, the chemistry is often unselective and produces numerous isomers. Waltz and Hartwig now report on a method for selectively activating the C-H bonds on the terminal carbon atoms. Transition-metal complexes bearing an electropositive boron atom generated alkylboronate esters photochemically; a tungsten complex proved to be the most reactive.

  14. Modifying a co-activator

    Variations in gene expression in different cell types result from the presence or activity of different transcription factors in those tissues. In B cells, complexes containing the octamer binding protein (Oct) and the BOB.1 co-activator are required for B cell-specific gene regulation. BOB.1 is constitutively expressed in B cells but is inducible in T cells. Zwilling et al. show that tissue-specific gene expression in T cells also requires BOB.1 and that this co-activator must be phosphorylated for activated gene expression. BOB.1 phosphorylation was required for both constitutive and inducible gene expression in B cells and T cells, respectively. Thus, posttranslational modification of a co-activator provides an additional means for regulating transcription. [See the Perspective by Graef and Crabtree.]

  15. Tumor cells on the move

    When tumor cells invade other tissues they must navigate through the extracellular matrix (ECM), a complex mixture of structural proteins and polysaccharide-rich molecules. This invasion process requires proteases, but whether these proteases simply remove physical barriers or provide signals for the cells to begin migration has been unclear. Giannelli et al. provide evidence for the latter. They show that matrix metalloprotease-2 induces migration of breast cancer cells by site-specific cleavage of the ECM component laminin-5. This cleavage is thought to expose a cryptic site in laminin-5 that triggers cell migration.

  16. Brain fates

    Early in vertebrate development, cells of the neurectoderm receive a variety of signals that define the ultimate structure of the central nervous system. Woo and Fraser show that, in the zebrafish, these signals fall into two categories. During gastrulation, signals from the embryonic organizer, the shield, define a general neural fate for the relevant portion of the ectoderm. Signals from the germring, away from the medial axis, define more specific antero-posterior fates of the pre-neural cells, such as whether the developing structures will be those of the forebrain or hindbrain. [See the cover.]

  17. Biogeochemical cycles

    To examine factors that influence the exchange of inorganic carbon between lakes and the atmosphere, Schindler et al. manipulated conditions in four initially similar lakes. The role of nutrient levels was assessed by artificial fertilization: Nutrient-enriched lakes became sinks for atmospheric carbon as they became more productive. Food web structure also had a significant influence: The absence of the top predator, piscivorous fish, caused lakes to become bigger net carbon sinks because of increased primary production. This integration of food web structure, primary production, and nutrient loading with carbon flux offers a new insight into how human activities may alter biogeochemical cycles.

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