This Week in Science

Science  06 Feb 2004:
Vol. 303, Issue 5659, pp. 725
  1. Managing Cellular Adhesions During Movement

    During migration, microtubules are stabilized at the cell's leading edge. At the same time, focal adhesions form in this region and integrins at the cell surface associate with the extracellular matrix to initiate adhesion-induced signals. Palazzo et al. (p. 836; see the Perspective by Guan) report that a signaling pathway that manages microtubule stability through the small guanosine triphosphate (GTP)-binding protein Rho is linked to an integrin-mediated signaling pathway at the leading edge. Specific membrane microdomains at the cell surface may serve as an intermediary to facilitate pathway interaction. Similar membrane microdomains are also targeted by the Rho-related protein Rac. Del Pozo et al. (p. 839; see the Perspective by Guan) found that when cells detach from extracellular matrix, such membrane microdomains and their associated Rac are internalized, which prevents downstream signaling events in the integrin-Rac pathway that controls processes such as cell migration.

  2. Magnetic Iron Nanocubes

    As electronic devices continue to shrink, new methods are required for the assembly of ordered nanometer-sized objects as lithography begins to hit its lower-end size limits. A number of magnetic materials have been fabricated into superlattices through the decomposition of organometallic precursors, but for particles based on iron, those that have been fabricated have shown diminished magnetization. Iron is of particular interest for magnetic devices, because iron has both a high magnetization and one can make alloys with a wide range of magnetic anisotropy. Dumestre et al. (p. 821) have hit upon a recipe for making superlattices of body-centered-cubic iron nanoparticles with magnetization that matches that of bulk iron.

  3. Amazonian Climate Change

    The lower cloud forests of the eastern Andes are areas of great biodiversity, and Bush et al. (p. 827) investigated how forest composition changed there during the past 48,000 years using pollen records recovered from sediments from Lake Consuelo. They infer from the distribution of species that the last ice age was between 5° and 9°C cooler than at present. Additionally, based on observed rates of forest community change, they estimate that temperature change in the lowland tropics was substantial but not rapid (about 1°C per 1000 years). A temperature rise of similar magnitude, but projected to occur in only the next 100 years, could select against species that have small bioclimatic envelopes and are slow to disperse.

  4. Nanoscale Thermoelectric Characterization

    Thermoelectric materials can directly convert heat to electricity, or they can be run in reverse as quiet refrigeration units. However, cost-effective power generation applications require device efficiencies in excess of 20% and a subsequent ZT factor (the characterization factor that takes into account the electronic and thermal properties of the material) between 2 and 3. The rather low ZT factor of bulk materials to date of ∼1 set the operating temperatures of interest at >800 kelvin and has hampered their widespread application (see the Perspective by Majumdar). Hsu et al. (p. 818) present results showing that a new family of materials based on cubic AgPbmSbTe2+m exhibits a ZT of ∼2.2 at 800 kelvin, which meets one of the basic requirements for efficient power generation. Lyeo et al. (p. 816) have developed a scanning probe technique to map the thermopower and related electronic properties of semiconductor junctions with nanometer resolution that should prove useful in the characterization and development of new nanostructured thermoelectric materials.

  5. Bad Neighbors?

    The most common forms of cancer arise through uncontrolled proliferation of epithelial cells. Although the growth of these cells is driven by their accumulation of genetic alterations, there is increasing evidence, largely derived from tissue culture studies, that tumor cell behavior is also regulated by surrounding stromal cells. Using a targeted gene inactivation strategy in mice, Bhowmick et al. (p. 848; see the Perspective by Radisky and Bissell) show that loss of transforming growth factor-β signaling in fibroblasts causes neoplastic progression of neighboring epithelial cells in the prostate and stomach. This effect appears to arise in part to increased production of hepatocyte growth factor by the genetically altered fibroblasts.

  6. Genetic Interaction Network

    Understanding the topology of genetic networks and their functional order may enable human geneticists to develop new approaches for identifying disease genes associated with complex traits. Tong et al. (p. 808; see the Perspective by Hartwell) have used double mutants to examine the network of genetic interactions in yeast. The yeast genetic network appeared to have 5 to 10 times the complexity of the protein interaction network, although it also followed a power law distribution and exhibited small-world properties. The position and connectivity of a gene within the network made it possible to predict molecular roles for previously uncharacterized genes that were supported by experimental data.

  7. No Halfway Virulence

    Conventional models for predicting the spread of infections usually assume that a host population is free-mixing. Boots et al. (p. 842) show that if you make allowances for host social structure in such models, for example, from dense and closed populations to open and mobile populations, then the virulence of a pathogen emerging within the population is affected. Rabbit hemorrhagic disease (RHD) virus was used as a proxy for human virus infections, and field-collected data was run in the model. Infection with RHD is normally symptom-free, but occasionally a recombination event allows an extremely virulent strain to emerge and become established. Similarly, the outcome of the model flipped between avirulence when host populations were closed to virulent in mobile populations.

  8. Uncovering Biotic Clay Formation

    During burial and heating of sediments, the clay mineral smectite gradually transforms to illite. This reaction, which appears to be closely tied to the generation of oil in sediment basins, has been thought that the reaction was entirely abiotic and to require burial, heat, and time to proceed. Kim et al. (p. 830) now show that bacteria, by reducing the Fe in smectite, can catalyze the reaction rapidly under ambient conditions. Thus, some of the natural occurrences of illite forming from smectite might reflect bacterial processes rather than just burial conditions.

  9. Cancer Drug in the Pocket

    The p53 pathway plays a pivotal role in the prevention of tumor development and has elicited considerable interest as a potential target for cancer drug discovery. In a systematic screen of synthetic chemicals, Vassilev et al. (p. 844) identified a series of small molecules (cis-imidazoline analogs, called “nutlins”) that inhibit the interaction of p53 with MDM2, a protein that antagonizes p53's tumor suppressor function. The nutlins act by binding MDM2 within its p53-binding pocket, resulting in p53 activation in tumor cells with subsequent cell cycle arrest and apoptosis. When orally administered to mice, the nutlins significantly inhibited tumor growth. These results validate the concept that small molecules targeting protein-protein interactions can be developed into effective therapeutics.

  10. Probing Three-Body Problems

    Autoionization of a doubly excited atom is an example of a three-body interaction, and like all three-body problems, the details of dynamics and energy exchange between electrons is a difficult one to solve, either computationally or experimentally. Pisharody and Jones (p. 813; see the Perspective by Stroud) show that coherent laser control of atomic electron wave packets can open up this problem. By simultaneously controlling the positions and momenta of two highly excited electrons within the same atom, they can probe the electron dynamics and interaction within the atom and obtain information regarding the decay process of these fragile atoms. Single violent electron-electron collision, rather than a gradual exchange of energy during “soft” collisions, leads to autoionization.

  11. Hiding Out in the Gall Bladder

    The food-poisoning bacterium Listeria monocytogenes, as well as other pathogens, replicates in the liver and are shed in bile as the liver cells break down. Using in vivo bioluminescent imaging of intact, live mice Hardy et al. (p. 851) show that L. monocytogenes can apparently also multiply in the gall bladder. This finding may explain several features of human listeriosis, including immune evasion, intrinsic resistance to antibiotic treatment, and asymptomatic carriage.

  12. Dopamine D2 Receptor Function Unraveled

    Cortical dopaminergic systems are involved in normal and abnormal cognition. Dopaminergic D2 antagonists are widely used in the treatment of schizophrenia. During the performance of tasks requiring working memory, cells in the frontal cortex discharge in relation to the memory period or in relation to guided memory saccades. Wang et al. (p. 853) applied D2 and D1 agonists and antagonists to single neurons in the brains of awake, behaving monkeys. Dopamine D2 receptors selectively controlled the activity associated with making memory-guided saccades, whereas D1 receptors controlled the persistent activity during the memory period. Thus, D2 receptors control working-memory-related activities in the prefrontal cortex.

  13. Untangling Entanglement

    The ease with which a polymer flows when it is deformed is intimately connected to the way in which the individual chains entangle with each other. Although theories, most notably that of reptation, have come a long way to describing how the chains move among each other by defining a primitive pathway, there is no single definition of what constitutes an entanglement or tube. Using simulations, Everaers et al. (p. 823) were able to correlate the experimentally measured entanglement density with a simple definition of an entanglement. This result opens up the possibility for correlating macroscopic measurements of polymer rheology with an understanding of how the individual chains move between each other.

  14. Genome-Wide Functional Analysis

    An RNA interference-based screen on a genome-wide scale is likely to become one of the methods of choice for comprehensive functional genomic analysis due to its potential to rapidly and systematically identify genes that control a variety of cellular processes. Boutros et al. (p. 832) conducted such a screen of the Drosophila genome in tissue culture cells and identified new genes and orthologs of human disease genes that control cell growth and survival. The results provide new functional information for annotating the genome of this important model organism.

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