Conditional tissue-specific reduction in MnSOD induced oxidative stress in mouse RPE, leading to RPE dysfunction, damage to the choroid, and death of photoreceptor cells. The RPE oxidative stress did not cause drusen-like deposits, but the model recapitulated certain key aspects of the pathology of dry AMD and may be useful in testing therapies.

The ubiquitin/proteasome system has been proposed to play an important role in Alzheimer's disease (AD) pathogenesis. However, the critical factor(s) modulating both amyloid-beta peptide (Abeta) neurotoxicity and ubiquitin/proteasome system in AD are not known. We report the isolation of an unusual ubiquitin-conjugating enzyme, E2-25K/Hip-2, as a mediator of Abeta toxicity. The expression of E2-25K/Hip-2 was upregulated in the neurons exposed to Abeta(1-42) in vivo and in culture. Enzymatic activity of E2-25K/Hip-2 was required for both Abeta(1-42) neurotoxicity and inhibition of proteasome activity. E2-25K/Hip-2 functioned upstream of apoptosis signal-regulating kinase 1 (ASK1) and c-Jun N-terminal kinase (JNK) in Abeta(1-42) toxicity. Further, the ubiquitin mutant, UBB+1, a potent inhibitor of the proteasome which is found in Alzheimer's brains, was colocalized and functionally interacted with E2-25K/Hip-2 in mediating neurotoxicity. These results suggest that E2-25K/Hip-2 is a crucial factor in regulating Abeta neurotoxicity and could play a role in the pathogenesis of Alzheimer's disease.

Tighter CO2 emission standards from mobile sources are being legislated globally in order to address the concerns regarding anthropogenic climate change. Hence, automotive manufacturers have developed a variety of new propulsion systems, including battery electric, plug-in hybrid, and even fuel cell electric vehicles.[1] However, there is a general consensus that internal combustion engines will continue to dominate the market for the foreseeable future. [1,2] As such, fuel-efficient combustion technologies like diesel engines offer superior green-house gas reduction potential. One technical obstacle to broader diesel implementation is the required lean NOx aftertreatment system, especially to meet upcoming strict emission regulations. NOx is extremely difficult to reduce under an oxygen-rich environment.[3] Although its selective catalytic reduction by urea (urea-SCR) has recently been commercialized, the operation window of this technology is severely limited by the decomposition temperature (~ 200 °C) of urea into NH3 and by SCR catalyst deactivation at temperatures higher than 750 °C.[4]This prohibits closer placement of the catalyst to the engine, requiring an aggressive warm-up with extra fuel burning during the cold-start. Furthermore, when integrating a mandatory particulate filter in the modern diesel aftertreatment system to mitigate soot and ash, the frequent regeneration of diesel particulate filters is required before a certain accumulation of soot, resulting in large temperature spikes. Improvement of the thermal durability of the SCR catalysts would, therefore, be the key to maximizing the fuel efficiency, as well as to producing clean emissions from diesel engines. Metal-exchanged zeolites have drawn much attention as diesel vehicle SCR catalysts, and with copper-exchanged ZSM-5 and SSZ-13, which are medium-and small-pore zeolites with MFI and CHA topologies, respectively, [5] have been most widely studied for this reaction.[4] Cu-SSZ-13 has recently been implemented as the current standard catalyst in the mobile SCR technology because of its superior thermal durability compared to already known catalysts. When aged at 850 °C, however, even this catalyst, whose fresh form achieves greater than 90% NOx conversion at 250 -400 °C in steady state, loses its CHA structure and forms copper oxide (CuOx) species, leading to severe activity loss. [6] Although zeolite A (framework type LTA) is the first synthetic zeolite to be prepared, [7] its catalytic applications have long been severely restricted due to its poor thermal stability originating from the high framework Al content (Si/Al = 1.0). However, a recent success in the benzylimidazolium-mediated synthesis of its unprecedented high-silica (Si/Al > 8) form provides a key advantage in terms of structural stability with tunable loading of catalytically-active metal centers.[8] Here we report that when the copper ion exchange level increases to 100% (Cu/Al = 0.50), the high-silica (Si/Al = 16-23) Cu-LTA catalysts hydrothermally aged at 900 °C, i.e., t...

Amyloid-β (Aβ) neurotoxicity is believed to contribute to the pathogenesis of Alzheimer's disease (AD). Previously we found that E2-25K/Hip-2, an E2 ubiquitin-conjugating enzyme, mediates Aβ neurotoxicity. Here, we report that E2-25K/Hip-2 modulates caspase-12 activity via the ubiquitin/proteasome system. Levels of endoplasmic reticulum (ER)–resident caspase-12 are strongly up-regulated in the brains of AD model mice, where the enzyme colocalizes with E2-25K/Hip-2. Aβ increases expression of E2-25K/Hip-2, which then stabilizes caspase-12 protein by inhibiting proteasome activity. This increase in E2-25K/Hip-2 also induces proteolytic activation of caspase-12 through its ability to induce calpainlike activity. Knockdown of E2-25K/Hip-2 expression suppresses neuronal cell death triggered by ER stress, and thus caspase-12 is required for the E2-25K/Hip-2–mediated cell death. Finally, we find that E2-25K/Hip-2–deficient cortical neurons are resistant to Aβ toxicity and to the induction of ER stress and caspase-12 expression by Aβ. E2-25K/Hip-2 is thus an essential upstream regulator of the expression and activation of caspase-12 in ER stress–mediated Aβ neurotoxicity.

Neurochemical alterations associated with behavioral responses induced by re-exposure to nicotine have not been sufficiently characterized in the dorsal striatum. Herein, we report on changes in glutamate concentrations in the rat dorsal striatum associated with behavioral alterations after nicotine challenge. Nicotine challenge (0.4 mg/kg/day, subcutaneous) significantly increased extracellular glutamate concentrations up to the level observed with repeated nicotine administration. This increase occurred in parallel with an increase in behavioral changes in locomotor and rearing activities. In contrast, acute nicotine administration and nicotine withdrawal on days 1 and 6 did not alter glutamate levels or behavioral changes. Blockade of α7 nicotinic acetylcholine receptors (nAChRs) significantly decreased the nicotine challenge-induced increases in extracellular glutamate concentrations and locomotor and rearing activities. These findings suggest that behavioral changes in locomotor and rearing activities after re-exposure to nicotine are closely associated with hyperactivation of the glutamate response by stimulating α7 nAChRs in the rat dorsal striatum.

The structure of the new medium-pore aluminophosphate molecular sieve PST-6 is determined by the combined use of rotation electron diffraction tomography, synchrotron X-ray powder diffraction, and computer modeling. PST-6 was prepared by calcination of another new aluminophosphate material with an unknown structure synthesized using diethylamine as a structure-directing agent, which is thought to contain bridging hydroxy groups. PST-6 has 36 crystallographically distinct tetrahedral sites in the asymmetric unit and is thus crystallographically the most complex zeolitic structure ever solved.

Natural gecko adhesive structures consisting of angled setae, branched into thin spatulas, have remarkable properties including easily attachable and releasable anisotropic adhesion. The geometrically asymmetric structures lead to anisotropic adhesive properties. Inspired by the gecko, we fabricated an array of micropillars with asymmetric spatula pads from elastomeric materials. This paper describes the anisotropic properties of the micropillars with spatula pads as established by experimental measurements and observation together with finite element analysis. The results indicate that the structural difference of the spatula pad at one edge of the micropillar provides the anisotropic adhesive properties.

The reagents used for zeolite syntheses included tetraethylammonium bromide (TEABr, 98%, Aldrich), NaOH (50% aqueous solution, Aldrich), Ca(NO3)2·4H2O (98%, DC Chemical), aluminum hydroxide (Al(OH)3•1.0H2O (Aldrich), colloidal silica (Ludox AS-40, DuPont), and deionized water. The final composition of the synthesis mixture was 5.2TEABr·1.9Na2O·0.5Ca(NO3)2·xAl2O3·7.2SiO2·yH2O, where x and y are varied between 0.5 ≤ x ≤ 1.5 and 150 ≤ y ≤ 390, respectively. After being stirred at 80 °C for 24 h, the synthesis mixture was charged into Teflon-lined 23-mL autoclaves and heated to 145 °C under rotation (60 rpm) for 2 days. The solid products were recovered by filtration, washed repeatedly with water, and then dried overnight at room temperature. Materials CharacterizationPowder X-ray diffraction (XRD) patterns were recorded on a PANalytical X´Pert diffractometer (Cu Kα radiation) with an X´Celerator detector. Data were collected with a fixed divergence slit (0.50°) and Soller slits (incident and diffracted = 0.04 rad). Crystal morphology and average size were determined by a JEOL JSM-6510 scanning electron microscope (SEM). The CO2, CH4, and N2 adsorption isotherms were measured at 25 °C and at pressures up to 1.2 bar using a Mirae SI nanoPorosity-XG analyzer. Prior to the experiments, zeolite sample was evacuated at 250 °C for 6 h.Synchrotron powder XRD data for the solid product (a mixture of PST-25, PST-26, and PST-28) obtained from Run 8 in Table 1 were collected on the 9B beamline equipped with a ceramic furnace of the Pohang Acceleration Laboratory (PAL; Pohang, Korea) using monochromated X-rays (λ = 1.4865 Å). The detector arm of the vertical scan diffractometer consists of seven sets of Soller slits, flat Ge(111) crystal analyzers, anti-scatter baffles, and scintillation detectors, with each set separated by 20°. Data were obtained on the sample at room temperature in flat plate mode, with a step size of 0.01° and an overlap of 0.50° to the