Mouse models of cell death

Cell death is critical for the development and orderly maintenance of cellular homeostasis in metazoans. Developmental genetics in model systems, including Caenorhabditis elegans and Drosophila melanogaster, have helped to identify and order the components of cell-death pathways. An even more complex network of apoptotic pathways has evolved in higher organisms that possess homologs within each set of cell-death regulators. Whereas biochemical studies provide details of molecular mechanisms, genetic models reveal the essential physiologic roles. Transgenic and gene-ablated mice have helped to elucidate mammalian apoptotic pathways and identify the principal effect of each cell death regulator. Here, we review the details of the apoptotic machinery as revealed by mice deficient in critical components of cell-death pathways; we concentrate on cell-death regulators classified as members of the caspase and Bcl2 families or, broadly, as adaptors and mitochondrial released factors.     

Porcine factor V: cDNA cloning, gene mapping, three-dimensional protein modeling of membrane binding sites and comparative anatomy of domains

Factor V is a plasma protein essential for blood coagulation. This protein is involved in activated protein C resistance, the most common inherited thrombotic disorder known. We utilized the polymerase chain reaction to clone the porcine factor V gene by generating overlapping clones amplified with primers chosen by comparison with known nucleotide sequences. The porcine factor V cDNA contig encodes a predicted 2258-amino acid protein, making it the largest in comparison to the bovine, human, and murine proteins. Porcine factor V has the highest level of homology with bovine factor V, but also has high levels of conservation of important residues with all the species. Radiation hybrid mapping assigned the porcine factor V gene to chromosome 4. Three-dimensional models of factor V were generated and used to analyze membrane-binding sites in terms of conserved, and therefore likely important residues. Received 3 October 2000; revised 23 November 2000; accepted 6 December 2000     

Strongly linked current flow in polycrystalline forms of the superconductor MgB2

The discovery of superconductivity at 39 K in magnesium diboride, MgB2, raises many issues, a critical one being whether this material resembles a high-temperature copper oxide superconductor or a low-temperature metallic superconductor in terms of its behaviour in strong magnetic fields. Although the copper oxides exhibit very high transition temperatures, their in-field performance is compromized by their large anisotropy, the result of which is to restrict high bulk current densities to a region much less than the full magnetic-field-temperature (H-T) space over which superconductivity is found. Moreover, the weak coupling across grain boundaries makes transport current densities in untextured polycrystalline samples low and strongly sensitive to magnetic field. Here we report that, despite the multiphase, untextured, microscale, subdivided nature of our MgB2 samples, supercurrents flow throughout the material without exhibiting strong sensitivity to weak magnetic fields. Our combined magnetization, magneto-optical, microscopy and X-ray investigations show that the supercurrent density is mostly determined by flux pinning, rather than by the grain boundary connectivity. Our results therefore suggest that this new superconductor class is not compromized by weak-link problems, a conclusion of significance for practical applications if higher temperature analogues of this compound can be discovered.     

Gate-induced superconductivity in a solution-processed organic polymer film

The electrical and optical properties of conjugated polymers have received considerable attention in the context of potentially low-cost replacements for conventional metals and inorganic semiconductors. Charge transport in these organic materials has been characterized in both the doped-metallic and the semiconducting state, but superconductivity has not hitherto been observed in these polymers. Here we report a distinct metal-insulator transition and metallic levels of conductivity in a polymer field-effect transistor. The active material is solution-cast regioregular poly(3-hexylthiophene), which forms relatively well ordered films owing to self-organization, and which yields a high charge carrier mobility (0.05-0.1 cm2 V(-1) s(-1)) at room temperature. At temperatures below approximately 2.35 K with sheet carrier densities exceeding 2.5 x 10(14) cm(-2), the polythiophene film becomes superconducting. The appearance of superconductivity seems to be closely related to the self-assembly properties of the polymer, as the introduction of additional disorder is found to suppress superconductivity. Our findings therefore demonstrate the feasibility of tuning the electrical properties of conjugated polymers over the largest range possible-from insulating to superconducting.     

Evidence for mantle metasomatism by hydrous silicic melts derived from subducted oceanic crust

The low concentrations of niobium, tantalum and titanium observed in island-arc basalts are thought to result from modification of the sub-arc mantle by a metasomatic agent, deficient in these elements, that originates from within the subducted oceanic crust. Whether this agent is an hydrous fluid or a silica-rich melt has been discussed using mainly a trace-element approach and related to variable thermal regimes of subduction zones. Melting of basalt in the absence of fluid both requires high temperatures and yields melt compositions unlike those found in most modern or Mesozoic island arcs. Thus, metasomatism by fluids has been thought to be the most common situation. Here, however, we show that the melting of basalt under both H2O-added and low-temperature conditions can yield extremely alkali-rich silicic liquids, the alkali content of which increases with pressure. These liquids are deficient in titanium and in the elements niobium and tantalum and are virtually identical to glasses preserved in mantle xenoliths found in subduction zones and to veins found in exhumed metamorphic terranes of fossil convergent zones. We also found that the interaction between such liquids and mantle olivine produces modal mineralogies that are identical to those observed in metasomatized Alpine-type peridotites. We therefore suggest that mantle metasomatism by slab-derived melt is a more common process than previously thought.     

Unconscious priming eliminates automatic binding of colour and alphanumeric form in synaesthesia

Synaesthesia is an unusual perceptual phenomenon in which events in one sensory modality induce vivid sensations in another. Individuals may 'taste' shapes, 'hear' colours, or 'feel' sounds. Synaesthesia was first described over a century ago, but little is known about its underlying causes or its effects on cognition. Most reports have been anecdotal or have focused on isolated unusual cases. Here we report an investigation of 15 individuals with colour-graphemic synaesthesia, each of whom experiences idiosyncratic but highly consistent colours for letters and digits. Using a colour-form interference paradigm, we show that induced synaesthetic experiences cannot be consciously suppressed even when detrimental to task performance. In contrast, if letters and digits are presented briefly and masked, so that they are processed but unavailable for overt report, the synaesthesia is eliminated. These results show that synaesthetic experiences can be prevented despite substantial processing of the sensory stimuli that otherwise trigger them. We conclude that automatic binding of colour and alphanumeric form in synaesthesia arises after initial processes of letter and digit recognition are complete.     

Drought-induced guard cell signal transduction involves sphingosine-1-phosphate

Stomata form pores on leaf surfaces that regulate the uptake of CO2 for photosynthesis and the loss of water vapour during transpiration. An increase in the cytosolic concentration of free calcium ions ([Ca2+]cyt) is a common intermediate in many of the pathways leading to either opening or closure of the stomatal pore. This observation has prompted investigations into how specificity is controlled in calcium-based signalling systems in plants. One possible explanation is that each stimulus generates a unique increase in [Ca2+]cyt, or 'calcium signature', that dictates the outcome of the final response. It has been suggested that the key to generating a calcium signature, and hence to understanding how specificity is controlled, is the ability to access differentially the cellular machinery controlling calcium influx and release from internal stores. Here we report that sphingosine-1-phosphate is a new calcium-mobilizing molecule in plants. We show that after drought treatment sphingosine-1-phosphate levels increase, and we present evidence that this molecule is involved in the signal-transduction pathway linking the perception of abscisic acid to reductions in guard cell turgor.     

Electrical spin injection and accumulation at room temperature in an all-metal mesoscopic spin valve

Finding a means to generate, control and use spin-polarized currents represents an important challenge for spin-based electronics, or 'spintronics'. Spin currents and the associated phenomenon of spin accumulation can be realized by driving a current from a ferromagnetic electrode into a non-magnetic metal or semiconductor. This was first demonstrated over 15 years ago in a spin injection experiment on a single crystal aluminium bar at temperatures below 77 K. Recent experiments have demonstrated successful optical detection of spin injection in semiconductors, using either optical injection by circularly polarized light or electrical injection from a magnetic semiconductor. However, it has not been possible to achieve fully electrical spin injection and detection at room temperature. Here we report room-temperature electrical injection and detection of spin currents and observe spin accumulation in an all-metal lateral mesoscopic spin valve, where ferromagnetic electrodes are used to drive a spin-polarized current into crossed copper strips. We anticipate that larger signals should be obtainable by optimizing the choice of materials and device geometry.     

Shear-induced molecular precession in a hexatic Langmuir monolayer

Liquid crystalline behaviour is generally limited to a select group of specially designed bulk substances. By contrast, it is a common feature of simple molecular monolayers and other quasi-two-dimensional systems, which often possess a type of in-plane ordering that results from unbinding of dislocations-a 'hexatic' liquid crystalline phase. The flow of monolayers is closely related to molecular transport in biological membranes, affects foam and emulsion stability and is relevant to microfluidics research. For liquid crystalline phases, it is important to understand the coupling of the molecular orientation to the flow. Orientationally ordered (nematic) phases in bulk liquid crystals exhibit 'shear aligning' or 'tumbling' behaviour under shear, and are described quantitatively by Leslie-Ericksen theory. For hexatic monolayers, the effects of flow have been inferred from textures of Langmuir-Blodgett films and directly observed at the macroscopic level. However, there is no accepted model of hexatic flow at the molecular level. Here we report observations of a hexatic Langmuir monolayer that reveal continuous, shear-induced molecular precession, interrupted by occasional jump discontinuities. Although superficially similar to tumbling in a bulk nematic phase, the kinematic details are quite different and provide a possible mechanism for domain coarsening and eventual molecular alignment in monolayers. We explain the precession and jumps within a quantitative framework that involves coupling of molecular orientation to the local molecular hexatic 'lattice', which is continuously deformed by shear.