On-Line pH Measurement Cation Exchange Kinetics of Y3+-Exchanged Alginic Acid for Y2O3 Nanoparticles Synthesis.

A new sol-gel method that employs cation exchange from an aqueous metal ion solution with H+ ions of granulated alginic acid was developed for synthesizing high-purity Y2O3 nanoparticles. In this study, the cation exchange kinetics of H+~Y3+ in aqueous solution were analyzed using on-line pH technology and off-line inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. Pseudo 2nd-order models were utilized to evaluate the parameters of the kinetics, suggesting that the concentration of H+~Y3+ involved in the cation exchange reaction was 1:1.733. Further, a comprehensive understanding of the Y-ALG calcination process was developed using thermo-gravimetric analysis, along with results obtained from differential scanning calorimetry (TGA/DSC). A detailed analysis of the XRD Rietveld refinement plots revealed that the crystallite sizes of Y2O3 nanoparticles were about 4 nm (500 °C) and 15 nm (800 °C), respectively. Differential pulse voltammetry (DPV) was employed to investigate the electrochemical oxidation of catechol. The oxidation peak currents of catechol at Y2O3 (500 °C)/GCE and Y2O3 (800 °C)/GCE showed two stages linear function of concentration (2.0~20.0 × 10-6 mol/L, 20.0~60.0 × 10-6 mol/L). The results indicated that the detection limits were equal to 2.4 × 10-7 mol/L (Y2O3 (500 °C)/GCE) and 7.8 × 10-7 mol/L (Y2O3 (800 °C)/GCE). The study not only provided a method to synthesize metal oxide, but also proposed a promising on-line pH model to study cation exchange kinetics.

Bifunctional 3D POM-based coordination polymers for improved pseudocapacitance and catalytic oxidation performance.

Developing novel high-efficiency supercapacitors as energy storage devices to solve the energy crisis is of vital significance. Meanwhile, designing highly active and selective oxidation catalysts for various sulfides is desirable but still a big challenge. To work out these problems, three novel 3D POM-based coordination polymers (POMCPs), formulated as [{Ag6(pytz)4}{SiMo12O40}] (1), [{Cu3(pytz)4}{SiMo12O40}]·5.5H2O (2) and [{Cu6(pytz)6}{SiMo12O40}]·2H2O (3) (pytz = 4-(5-(4-pyridyl)-1H-tetrazole)), are successfully prepared via a one-step synthetic strategy by changing different temperatures under hydrothermal or solvothermal conditions. In compounds 1 and 2, {SiMo12}, as 9-capped and 2-capped polyoxoanions, are engaged among the 2D Ag/Cu-organic sheets to generate the novel 3D POM-based coordination polymers. In addition, 1D Cu-organic chains are combined with 3-capped {SiMo12} polyoxoanions to construct 2D POM-based coordination polymers in 3. To our delight, as electrode materials for supercapacitors, the three compounds exhibit excellent specific capacitances of 261.76 F g-1, 248.82 F g-1 and 156.47 F g-1 at 0.5 A g-1, respectively. Besides, they can effectively and selectively catalyze the oxidation of various sulfides to sulfoxides.

The BLOC-1 Subunit Pallidin Facilitates Activity-Dependent Synaptic Vesicle Recycling.

Membrane trafficking pathways must be exquisitely coordinated at synaptic terminals to maintain functionality, particularly during conditions of high activity. We have generated null mutations in the Drosophila homolog of pallidin, a central subunit of the biogenesis of lysosome-related organelles complex-1 (BLOC-1), to determine its role in synaptic development and physiology. We find that Pallidin localizes to presynaptic microtubules and cytoskeletal structures, and that the stability of Pallidin protein is highly dependent on the BLOC-1 components Dysbindin and Blos1. We demonstrate that the rapidly recycling vesicle pool is not sustained during high synaptic activity in pallidin mutants, leading to accelerated rundown and slowed recovery. Following intense activity, we observe a loss of early endosomes and a concomitant increase in tubular endosomal structures in synapses without Pallidin. Together, our data reveal that Pallidin subserves a key role in promoting efficient synaptic vesicle recycling and re-formation through early endosomes during sustained activity.

Bidirectional Regulation of Amyloid Precursor Protein-Induced Memory Defects by Nebula/DSCR1: A Protein Upregulated in Alzheimer's Disease and Down Syndrome.

Aging individuals with Down syndrome (DS) have an increased risk of developing Alzheimer's disease (AD), a neurodegenerative disorder characterized by impaired memory. Memory problems in both DS and AD individuals usually develop slowly and progressively get worse with age, but the cause of this age-dependent memory impairment is not well understood. This study examines the functional interactions between Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. Using Drosophila as a model, we find that overexpression of nebula (fly homolog of DSCR1) initially protects against APP-induced memory defects by correcting calcineurin and cAMP signaling pathways but accelerates the rate of memory loss and exacerbates mitochondrial dysfunction in older animals. We report that transient upregulation of Nebula/DSCR1 or acute pharmacological inhibition of calcineurin in aged flies protected against APP-induced memory loss. Our data suggest that calcineurin dyshomeostasis underlies age-dependent memory impairments and further imply that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory impairments in AD in DS. SIGNIFICANCE STATEMENT: Most Down syndrome (DS) individuals eventually develop Alzheimer's disease (AD)-like dementia, but mechanisms underlying this age-dependent memory impairment remain poorly understood. This study examines Nebula/Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. We uncover a previously unidentified role for Nebula/DSCR1 in modulating APP-induced memory defects during aging. We show that upregulation of Nebula/DSCR1, an inhibitor of calcineurin, rescues APP-induced memory defects in young flies but enhances memory loss of older flies. Excitingly, transient Nebula/DSCR1 overexpression or calcineurin inhibition in aged flies ameliorates APP-mediated memory problems. These results suggest that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory loss in DS and AD and points to correcting calcineurin signaling as a means to improve memory during aging.

Deprotonation-triggered Stokes shift fluorescence of an unexpected basic-stable metal-organic framework.

A new three-dimensional porous metal-organic framework, JUC-119, constructed by a pyrene-based dendritic organic linker, H8TIAPy (H8TIAPy = 1,3,6,8-tetrakis(3,5-isophthalic acid)pyrene), and Eu(III) has been synthesized successfully. JUC-119 shows unexpected stability under a wide range of basic conditions from 0 to 0.01 M NaOH. Furthermore, with two carboxyl groups uncoordinated in each ligand, the crystals of JUC-119 show deprotonation-triggered Stokes shift fluorescence under basic conditions. As the concentration of base increases from 0 to 0.01 M NaOH, the luminescence emission of JUC-119 becomes gradually red shifted from 455 to 485 nm. In addition, the Stokes shift shows a good linear relationship to -log[OH(-)], which makes JUC-119 promising for base sensing.

Intracellular antioxidants dissolve man-made antioxidant nanoparticles: using redox vulnerability of nanoceria to develop a responsive drug delivery system.

Regeneratable antioxidant property of nanoceria has widely been explored to minimize the deleterious influences of reactive oxygen species. Limited information is, however, available regarding the biological interactions and subsequent fate of nanoceria in body fluids. This study demonstrates a surprising dissolution of stable and ultrasmall (4 nm) cerium oxide nanoparticles (CeO2 NPs) in response to biologically prevalent antioxidant molecules (glutathione, vitamin C). Such a redox sensitive behavior of CeO2 NPs is subsequently exploited to design a redox responsive drug delivery system for transporting anticancer drug (camptothecin). Upon exposing the CeO2 capped and drug loaded nanoconstruct to vitamin c or glutathione, dissolution-accompanied aggregation of CeO2 nanolids unleashes the drug molecules from porous silica to achieve a significant anticancer activity. Besides stimuli responsive drug delivery, immobilization of nanoceria onto the surface of mesoporous silica also facilitates us to gain a basic insight into the biotransformation of CeO2 in physiological mediums.

Presynaptic inhibition of gamma lobe neurons is required for olfactory learning in Drosophila.

The loss of heterotrimeric G(o) signaling through the expression of pertussis toxin (PTX) within either the α/ß or γ lobe mushroom body neurons of Drosophila results in the impaired aversive olfactory associative memory formation. Herein, we focus on the cellular effects of G(o) signaling in the γ lobe mushroom body neurons during memory formation. Expression of PTX in the γ lobes specifically inhibits G(o) activation, leading to poor olfactory learning and an increase in odor-elicited synaptic vesicle release. In the γ lobe neurons, training decreases synaptic vesicle release elicited by the unpaired conditioned stimulus -, while leaving presynaptic activation by the paired conditioned stimulus + unchanged. PTX expression in γ lobe neurons inhibits the generation of this differential synaptic activation by conditioned stimuli after negative reinforcement. Hyperpolarization of the γ lobe neurons or the inhibition of presynaptic activity through the expression of dominant negative dynamin transgenes ameliorated the memory impairment caused by PTX, indicating that the disinhibition of these neurons by PTX was responsible for the poor memory formation. The role for γ lobe inhibition, carried out by G(o) activation, indicates that an inhibitory circuit involving these neurons plays a positive role in memory acquisition. This newly uncovered requirement for inhibition of odor-elicited activity within the γ lobes is consistent with these neurons serving as comparators during learning, perhaps as part of an odor salience modification mechanism.

Eco-friendly fabrication of hydrophilic ZSM-5 membranes for alcohol upgrading.

The synthesis of continuous and low-siliceous ZSM-5 membranes was achieved without organic templates under mild conditions (a low temperature of 100 °C and ambient pressure). The resultant high-quality membranes with good water perm-selectivity were further applied in water-alcohol separation, exhibiting an extraordinarily high separation factor of above 10,000 and an improved water flux (3.43-6.88 kg m(-2) h(-1)) for ethanol and isopropanol aqueous azeotropes.

mTORC2 controls actin polymerization required for consolidation of long-term memory.

A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short- to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.

Memory formation: traversing the highwire.

Molecules that suppress memory formation protect against the consolidation of inaccurate information. A recent study in Drosophila has identified a new pathway for memory suppression and the neurons that are a gateway to long-term memory formation.

G(o) activation is required for both appetitive and aversive memory acquisition in Drosophila.

Heterotrimeric G(o) is an abundant brain protein required for negatively reinforced short-term associative olfactory memory in Drosophila. G(o) is the only known substrate of the S1 subunit of pertussis toxin (PTX) in fly, and acute expression of PTX within the mushroom body neurons (MB) induces a reversible deficit in associative olfactory memory. We demonstrate here that the induction of PTX within the α/ß and γ lobe MB neurons leads to impaired memory acquisition without affecting memory stability. The induction of PTX within these MB neurons also leads to a significant defect in an optimized positively reinforced short-term memory paradigm; however, this PTX-induced learning deficit is noticeably less severe than found with the negatively reinforced paradigm. Both negatively and positively reinforced memory phenotypes are rescued by the constitutive expression of G(o)α transgenes bearing the Cys(351)Ile mutation. Since this mutation renders the G(o) molecule insensitive to PTX, the results isolate the effect of PTX on both forms of olfactory associative learning to the inhibition of the G(o) activation.

Choice strategies in Drosophila are based on competition between olfactory memories.

The brain mechanisms by which animals deal with multiple experiences to predict outcomes are not yet fully understood. We explored the choice strategies that flies use to assess degrees of disadvantage, as well as how flies weigh past and recent experiences to guide decisions. Drosophila were exposed to two conditioning events in a T-maze: an odor paired with an electric shock followed by a second odor paired with an electric shock of a different intensity. Subsequently, flies were forced to choose between the two odors. We found that flies chose to avoid the more 'dangerous' odor by a linear subtraction mechanism that was based on two coexisting memories. We also found that flies weighed experiences of the same danger level (60 V electric shocks) according to the times when the experiences had occurred. More recent experiences had a greater impact and past experiences gradually became 'overlooked' during decisions as the time delay between the two events lengthened. However, the past memory was not so much disrupted as it was overshadowed by recent memories during decisions. Finally, when a past experience was more disadvantageous, wild-type flies were able to coordinate both the temporal factor and the degree of disadvantage into their decisions. By contrast, amnesiac mutant flies made choices completely according to the temporal factor, ignoring the degree of disadvantage. Taken together, wild-type flies are able to store multiple olfactory memories and can coherently evaluate learned experiences to guide their decisions according to the degree of disadvantage and/or the temporal factor.

[Clinical observation on Jiquan (HT 1) for treatment of cervical spondylosis of nerve root type].

OBJECTIVE: To observe acupuncture at Jiquan (HT 1) with different manipulations for improvement of abnormal sensation of the upper limb induced by cervical spondylosis of nerve root type. METHODS: One hundred and seven cases were randomly divided into 3 groups. The lifting-thrusting group (n = 37) were treated with acupuncture at Jiquan (HT 1) with lifting-thrusting manipulation, the twirling group (n = 36) with acupuncture at Jiquan (HT 1) with twirling manipulation and the routine needling group (n = 34) with acupuncture at C4 - T1 Jiaji (EX-B 2), Quchi (LI 11). RESULTS: The total effective rate of 91.9% in the lifting-thrusting group was significantly better than 58.3% in the twirling group (P < 0.005) and 76.5% in the routine needling group (P < 0.05), and the therapeutic effect of the twirling group was similar to that in the routine needling group CP > 0.05). CONCLUSION: Acupuncture at Jiquan (HT 1) with lifting-thrusting manipulation can obviously improve abnormal sensation of the upper limb induced by cervical spondylosis of nerve root type.

Increased dopaminergic signaling impairs aversive olfactory memory retention in Drosophila.

Dopamine is necessary for the aversive olfactory associative memory formation in Drosophila, but its effect on other stages of memory is not known. Herein, we studied the effect of enhanced dopaminergic signaling on aversive olfactory memory retention in flies. We used l-3,4-dihydroxyphenylalanine (l-DOPA) to elevate dopamine levels: l-DOPA-treated flies exhibited a normal learning performance, but a decrease in 1-h memory. Dopamine transporter (DAT) mutant flies or flies treated with the DAT inhibitor desipramine exhibited poor memory retention. Flies subjected to heat stress after training exhibited a decrease in memory. Memory was restored by blocking dopaminergic neuronal output during heat stress, suggesting that dopamine is involved in heat stress-induced memory impairment in flies. Taken together, our findings suggest that increased dopaminergic signaling impairs aversive olfactory memory retention in flies.