Delaying a model prion disease
Protease-resistant forms of prion proteins (PrPres) are thought to be involved in Creutzfeldt-Jakob disease in humans and the spongiform encephalopathies of cattle that appear to have recently spread to human populations. The structure of PrPres has features that resemble those of amyloid proteins. A derivative of doxorubicin, IDX, has previously been used to treat patients with different cancers and has been shown to bind strongly to amyloid fibers. In a model system for prion diseases, experimental scrapie induced by injection of brain material into Syrian hamsters, Tagliavini et al. (p. 1119) show that symptoms of disease were delayed if the animals were simultaneously treated with IDX.
Ferroelectric materials are of interest for device construction because their characteristic polarization field, which can be reversed, remains after power is shut off to the circuit. Ahn et al. (p. 1100) show that micrometer-size areas of different polarizations could be written into high-quality heterostructures of lead strontium titanate and strontium ruthenate. A metallized atomic force microscope tip, scanning in a noncontact mode, provided the local electric field for changing the polarization in these ferroelectric films.
Saturated x-ray lasers
Practical applications of x-ray lasers would require that their output be saturated so that they are stable and produce the maximum operating power. Many of the materials used for the plasmas that produce the x-rays require steep increases in driving laser power for wavelengths below 10 nanometers. Zhang et al. (p. 1097) demonstrate an efficient saturated samarium x-ray laser operating at 7 nanometers. A low-intensity laser prepulse is used to produce a more uniform plasma for the main excitation laser pulse.
Wetter, but when?
Chondrites are thought to represent the most primitive materials found in meteorites, and carbonaceous chondrites have exhibited inclusions of relatively rare hydrous mineral phases. Brearley (p. 1103), using high-resolution transmission electron microscopy, has found more abundant and widespread hydrous phases that replace pyroxenes along fractures in seven carbonaceous chondrules from the Allende meteorite. The author discusses whether this aqueous alteration occurred in the preaccretionary, nebular stage or while the chondrules resided on the meteorite's parent body.
Data from the magnetometer on board the Galileo orbiter has indicated that two of the jovian satellites, Io and Ganymede, have intrinsic magnetic fields. Sarson et al. (p. 1106) performed two-dimensional magnetohydrodynamic simulations and found that Ganymede's field is probably produced by its own dynamo, suggesting that the largest of the Galilean satellites has internal convection. For Io, which has active volcanism (considered to be a surface expression of a convecting interior) and also orbits closer to Jupiter than Ganymede, the simulations cannot distinguish between an internal dynamo or generation of Io's field by the ambient jovian magnetic field.
Individual molecules of titin, a component of striated muscle, are of the order of a micrometer in length and are thought to provide a passive restoring force as muscles elongate. How is this force generated and what is its magnitude? Rief et al. (p. 1109), using atomic force microscopy, and Kellermayer et al. (p. 1112), using laser tweezers, measured the mechanical properties of single titin molecules (see the Perspective by Erickson, p. 1090). Pulling extends the molecule in 25-nanometer increments, corresponding to the stepwise unfolding of tandemly arrayed immunoglobulin domains, and the measured forces depend on the rate of extension, approaching several hundred piconewtons at an extension rate of 1 micrometer per second. Release or relaxation allows both for rapid refolding and for the measurement of entropic elasticity. Scaling these data to macroscopic dimensions reproduces measurements made on whole muscle fibers.
Laying down plans
The basic axes of the vertebrate body plan are established early in oogenesis, when RNA molecules are localized to specific regions of the oocyte. The localized RNA molecules then remain quiescent, awaiting later times in development to be translated into protein. In the frog, Xenopus, one of the more important RNA molecules encodes Vg1, a growth factor that directs mesoderm development. Deshler et al. (p. 1128; see the Perspective by Etkin, p. 1092) show that localization of Vg1 mRNA to the oocyte's vegetal pole involves interaction with a protein named Vera and an association with a specialized fraction of the endoplasmic reticulum.
Oligosaccharides on cell surfaces can be chemically modified to present unusual functional groups for recognition or reaction. Mahal et al. (p. 1125) incorporated an unnatural derivative of N-acetylmannosamine bearing a ketone group into cells, where it was converted metabolically into a cell surface molecule. The ketones could be used to attach a biotin tag to the cell; this in turn allowed selective lethal targeting of cells with a ricin A chain attached to avidin, which binds to biotin.
Many practical problems in physics, chemistry, and engineering require that some optimum set of parameters. Global optimization tries to find the maximum or minimum value of a function that depends on several variables, much like a hiker finding the lowest mountain valley. Many local minima, isolated valleys that are not the lowest valley, may be found while missing the true optimum. Barhen et al. report a new algorithm for global optimization—terminal repeller unconstrained subenergy tunneling, or TRUST—that is deterministic and easy to implement. Performance tests indicate that TRUST is faster and more accurate than previously reported techniques. As an example, the authors present its use in a classic problem in seismology.
The fungus that causes rice blast disease is responsible for tremendous cost and effort in managing the agricultural impact of the disease. In studying the interaction between fungal cells and the host rice plant, Beckerman et al. find that a peptide pheromone regulates development of the invasive cell type. A pheromone that regulates mating in a distantly related fungus, bakers' yeast, can mimic these effects, indicating that evolution may have conserved certain pheromone signaling pathways in fungi. Characterization of the pheromone that regulates the plant-fungal interaction may lead to new routes to manage the disease.
When the human malaria parasite Plasmodium falciparum infects a red blood cell, it assembles a network of tubovesicular membranes (TVM) that extends from the parasite vacuolar membrane to the periphery of the cell. The function of the TVM has been unclear. Lauer et al. show that prevention of TVM assembly also prevents delivery of small solutes, such as amino acids and nucleosides, from the extracellular medium to the parasite. The parasite apparently uses the TVM as a transport network for nutrients. [See the news story by Vogel.]