Amyloid β-induced FOXRED2 mediates neuronal cell death via inhibition of proteasome activity

Proteasome inhibition has been regarded as one of the mediators of Aβ neurotoxicity. In this study, we found that FOXRED2, a novel endoplasmic reticulum (ER) residential protein, is highly up-regulated by Aβ in rat cortical neurons and SH-SY5Y cells. Over-expression of FOXRED2 inhibits proteasome activity in the microsomal fractions containing ER and interferes with proteasome assembly, as evidenced by gel filtration and native gel electrophoresis analysis. In contrast, reduced expression of FOXRED2 rescues Aβ-induced inhibition of proteasome activity. FOXRED2 is an unstable protein with two degradation boxes and one KEN box, and its N-terminal oxidoreductase domain is required for proteasome inhibition. Ectopic expression of FOXRED2 induces ER stress-mediated cell death via caspase-12, which is inhibited by Salubrinal. Further, down-regulation of FOXRED2 expression attenuates Aβ-induced cell death and the ER stress response. These results suggest that up-regulated FOXRED2 inhibits proteasome activity by interfering with 26S proteasome assembly to contribute to Aβ neurotoxicity via an ER stress response.     

The post-spinel transformation in Mg2SiO4 and its relation to the 660-km seismic discontinuity

The 660-km seismic discontinuity in the Earth's mantle has long been identified with the transformation of (Mg,Fe)2SiO4 from gamma-spinel (ringwoodite) to (Mg,Fe)SiO3-perovskite and (Mg,Fe)O-magnesiowüstite. This has been based on experimental studies of materials quenched from high pressure and temperature, which have shown that the transformation is consistent with the seismically observed sharpness and the depth of the discontinuity at expected mantle temperatures. But the first in situ examination of this phase transformation in Mg2SiO4 using a multi-anvil press indicated that the transformation occurs at a pressure about 2 GPa lower than previously thought (equivalent to approximately 600 km depth) and hence that it may not be associated with the 660-km discontinuity. Here we report the results of an in situ study of Mg2SiO4 at pressures of 20-36 GPa using a combination of double-sided laser-heating and synchrotron X-ray diffraction in a diamond-anvil cell. The phase transformation from gamma-Mg2SiO4 to MgSiO3-perovskite and MgO (periclase) is readily observed in both the forward and reverse directions. In contrast to the in situ multi-anvil-press study, we find that the pressure and temperature of the post-spinel transformation in Mg2SiO4 is consistent with seismic observations for the 660-km discontinuity.     

n-type colloidal semiconductor nanocrystals

Colloidal semiconductor nanocrystals combine the physical and chemical properties of molecules with the optoelectronic properties of semiconductors. Their colour is highly controllable, a direct consequence of quantum confinement on the electronic states. Such nanocrystals are a form of 'artificial atoms' (ref. 4) that may find applications in optoelectronic systems such as light-emitting diodes and photovoltaic cells, or as components of future nanoelectronic devices. The ability to control the electron occupation (especially in n-type or p-type nanocrystals) is important for tailoring the electrical and optical properties, and should lead to a wider range of practical devices. But conventional doping by introducing impurity atoms has been unsuccessful so far: impurities tend to be expelled from the small crystalline cores (as observed for magnetic impurities), and thermal ionization of the impurities (which provides free carriers) is hindered by strong confinement. Here we report the fabrication of n-type nanocrystals using an electron transfer approach commonly employed in the field of conducting organic polymers. We find that semiconductor nanocrystals prepared as colloids can be made n-type, with electrons in quantum confined states.     

Medium-scale carbon nanotube thin-film integrated circuits on flexible plastic substrates

The ability to form integrated circuits on flexible sheets of plastic enables attributes (for example conformal and flexible formats and lightweight and shock resistant construction) in electronic devices that are difficult or impossible to achieve with technologies that use semiconductor wafers or glass plates as substrates. Organic small-molecule and polymer-based materials represent the most widely explored types of semiconductors for such flexible circuitry. Although these materials and those that use films or nanostructures of inorganics have promise for certain applications, existing demonstrations of them in circuits on plastic indicate modest performance characteristics that might restrict the application possibilities. Here we report implementations of a comparatively high-performance carbon-based semiconductor consisting of sub-monolayer, random networks of single-walled carbon nanotubes to yield small- to medium-scale integrated digital circuits, composed of up to nearly 100 transistors on plastic substrates. Transistors in these integrated circuits have excellent properties: mobilities as high as 80 cm(2) V(-1) s(-1), subthreshold slopes as low as 140 m V dec(-1), operating voltages less than 5 V together with deterministic control over the threshold voltages, on/off ratios as high as 10(5), switching speeds in the kilohertz range even for coarse (approximately 100-microm) device geometries, and good mechanical flexibility-all with levels of uniformity and reproducibility that enable high-yield fabrication of integrated circuits. Theoretical calculations, in contexts ranging from heterogeneous percolative transport through the networks to compact models for the transistors to circuit level simulations, provide quantitative and predictive understanding of these systems. Taken together, these results suggest that sub-monolayer films of single-walled carbon nanotubes are attractive materials for flexible integrated circuits, with many potential areas of application in consumer and other areas of electronics.     

TMEM16A confers receptor-activated calcium-dependent chloride conductance

Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remained largely unknown. Here we show that transmembrane protein 16A (TMEM16A, which we also call anoctamin 1 (ANO1)) is a bona fide Ca(2+)-activated chloride channel that is activated by intracellular Ca(2+) and Ca(2+)-mobilizing stimuli. With eight putative transmembrane domains and no apparent similarity to previously characterized channels, ANO1 defines a new family of ionic channels. The biophysical properties as well as the pharmacological profile of ANO1 are in full agreement with native Ca(2+)-activated chloride currents. ANO1 is expressed in various secretory epithelia, the retina and sensory neurons. Furthermore, knockdown of mouse Ano1 markedly reduced native Ca(2+)-activated chloride currents as well as saliva production in mice. We conclude that ANO1 is a candidate Ca(2+)-activated chloride channel that mediates receptor-activated chloride currents in diverse physiological processes.