This Week in Science

Science  18 Mar 2005:
Vol. 307, Issue 5716, pp. 1687
  1. Letting Ras Know Where It's At


    The correct spatial organization of cellular signaling molecules is crucial to ensuring proper biological response. Some signaling proteins, such as the Ras guanosine triphosphatases, are modified by lipids that direct their localization to the plasma membrane and to intracellular membranes of the Golgi complex. Ras proteins are thought to acquire these lipid moieties while transiting through the secretory pathway. Rocks et al. (p. 1746, published online 10 February 2005, see the Perspective by Meder and Simons) now find that Ras becomes depalmitoylated at the plasma membrane, releasing the protein to the cytoplasm. Released Ras that is redistributed to the Golgi becomes repalmitoylated and subsequently transported to the cell surface, where the acylation cycle begins again. These changes in palmitoylation correlate with Ras signaling and provide a mechanism for controlling Ras protein intracellular distribution.

  2. Collagen as Oncoprotein

    Patients with an inherited skin disorder called recessive dystrophic epidermolysis bullosa (RDEB) often develop squamous cell carcinoma, a form of skin cancer that is common in the general population. RDEB is caused by mutations in the gene encoding the extracellular matrix (ECM) protein collagen VII, but the role of collagen in cancer development has been unclear. Ortiz-Urda et al. (p. 1773; see the Perspective by Yuspa and Epstein) now show that RDEB patients who develop cancer express an aberrant, truncated version of collagen VII that confers tumorigenic properties to skin cells, by enhancing their ability to invade surrounding tissue. In mice, tumor induction can be blocked by administration of antibodies targeting this collagen fragment. These results highlight the critical role of the ECM in tumorigenesis and suggest that ECM proteins may be valuable therapeutic targets for certain forms of cancer.

  3. The Good Food Sense

    Some animals can recognize that a meal is deficient in amino acids, and thus reject such offerings within 20 minutes. This behavioral response to amino acid deficiency in omnivores has been known for some time, but the nutrient sensor has eluded discovery. Hao et al. (p. 1776) found that an ancient amino acid sensing mechanism found in yeast is conserved in the neurons of the anterior piriform cortex. This amino acid chemosensory brain area projects to neural circuits controlling food intake.

  4. Thermal Inertia and Climate


    If the emission of greenhouse gases were to stop today, their associated global warming would continue because of the long lifetime of the gases in the atmosphere and thermal inertia of the ocean, and sea level rise would continue because of thermal expansion. Two modeling studies address these issues. Wigley (p. 1766) discusses the long-term climate warming commitment we have made already, as well as that which would occur under the still highly optimistic scenario of no further rise in the rate of greenhouse gas emissions. Meehl et al. (p. 1769) quantify how much more global warming and sea level rise (just from thermal expansion) could be expected had greenhouse gas concentrations been frozen at their 2000 levels. Both studies conclude that even in these best-case scenarios, temperatures will rise by as much as 0.5°C and sea level will rise by tens of centimeters, not including any melting from ice sheets and glaciers.

  5. Radio-Controlled Electrons

    Although atoms are often depicted with discrete electrons orbiting the nucleus, electrons are more properly described as delocalized clouds. However, under the right excitation conditions, the classical model can pertain. When electrons are excited sufficiently that the level spacing is much smaller than the total energy, they can occupy several levels at once. This delocalization in energy leads to a corresponding localization in space, and temporarily the electrons resemble classical orbiting particles. Maeda et al. (p. 1757, published online 10 February 2005, see the Perspective by Villeneuve) have stabilized Li atoms in this state by applying a microwave field tuned to the orbiting frequency. They further show that by adjusting the microwave frequency, they can fine-tune the period and radius of the electron orbit, along with the corresponding binding energy.

  6. Probing Polymer Creep and Crystallization

    The motion of polymer chains in thin films is complex; the presence of a free surface should allow for greater degrees of freedom in their motion, but the reduced dimension of the film restricts mobility. These effects are reflected in the glass transition temperature and the rheology of the films. O'Connell and McKenna (p. 1760) use the inflation of a bubble to measure the compliance of thin polymer films. While they see no changes in the glass transition temperature, they do see dramatic changes in the film's elasticity. For polymers that can partially crystallize, the crystallization process is relatively slow. The morphologies that form depend on the processing conditions, the orientations of chains before solidification, and residual stresses. Liu et al. (p. 1763) have devised an atomic force microscope that can deliver polymer chains and take images at the same time, thus allowing for exquisite control and observation of the crystallization.

  7. Breaking Up Is Hard To Do

    Proper cell division—the formation of two daughter cells from a single mother cell—involves mitosis, during which duplicated chromosomes are separated, and cytokinesis, the separation of the two daughter cells. Glotzer (p. 1735) reviews what is known about the cellular mechanisms involved in cytokinesis in a variety of cellular systems. Coordination of cytokinesis with chromosome congression and segregation is critical for proper cell division. In a Report, Spiliotis et al. (p. 1781) describe their study of a conserved family of binding proteins known as the septins that localize to the metaphase plate during mammalian mitotis. Septin depletion disrupted the accumulation of chromosomes and their segregation and led to defects in cytokinesis. These defects correlated with a failure of CENP-E, a mitotic motor and mitotic checkpoint regulator, to localize correctly on congressing chromosomes. Mammalian septins may thus form a mitotic scaffold that coordinates chromosome congression and segregation with cytokinesis.

  8. Change Down Under

    The ocean process most commonly associated with global climate change is the formation of deep water in the North Atlantic, but a growing body of observations and model results implicate other parts of the ocean, particularly in the Southern Hemisphere. Pahnke and Zahn (p. 1741) examine the role of Antarctic Intermediate Water (AAIW), which forms in the southern mid-latitudes and is found at depths between 500 and 100 meters, in redistributing heat and fresh water within the deeper oceans. Changes in AAIW formation during the last 340,000 years were coupled to variations in North Atlantic deep water formation and climate change in the Antarctic. The contemporaneous responses implicate the atmosphere in forcing the climate changes.

  9. The Eyes--and the Swimbladder--Have It


    Teleost fishes maintain buoyancy using a gas-inflated swimbladder. Oxygen is pumped into the swimbladder by means of a complex arrangement of veins and arteries, known as the rete mirabile, and special pH sensitive “root-effect” hemoglobins, which also have low specific buffer values. A Na+/H+ exchanger regulates the intracellular pH of red blood cells. Many fish also have an ocular rete mirabile to support the high metabolic activity of the avascular fish retina. Berenbrink et al. (p. 1752) use phylogenetics, the biochemistry and structure of hemoglobins, and details of the activity of the Na+/H+ exchanger in extant fishes to explain the evolution this complex system. Root-effect hemoglobins must have appeared before the rete mirabile. The ocular retia—which required the presence of the Na+/H+ exchanger—likely evolved 100 million years before the swimbladder retia, whose appearance correlates with significant adaptive radiation in teleost fish.

  10. Sugary Coating

    How do humans tolerate the presence of billions of bacteria in the gut without mounting an inflammatory response? Coyne et al. (p. 1778) analyze the most common bacterial genus found in the human intestine (Bacteroides) and show that these organisms decorate their capsular polysaccharides and surface glycoproteins with L-fucose. L-Fucose is abundant on the surface of intestinal epithelial cells, and Bacteroides stimulates intestinal epithelial cells to express fucosylated molecules. This molecular mimicry allows Bacteroides to be tolerated by the host.

  11. The Right Stuff for Wing Formation

    Animal organs and appendages are comprised of cells with different morphologies. For example, the Drosophila wing primordium displays cells that are squamous, cuboidal, or columnar. What are the molecular determinants for this cell variation? Gibson and Perrimon (p. 1785) examine this question by screening flies with defects in epithelial cell morphogenesis in the wing. Mutation of a signaling receptor produced a wing defect in which cells are extruded from the epithelial surface. Contrary to earlier work that implicated this signaling pathway in cell survival, it appears that the signaling pathway is instead involved in epithelial organization, and any subsequent cell death is a secondary effect. Similar conclusions are also reached by Shen and Dahmann (p. 1789).

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