Toxicities of amyloid-beta and tau protein are reciprocally enhanced in the Drosophila model

Extracellular aggregation of amyloid-beta(Aβ)and intracellular tau tangles are two major pathogenic hallmarks and critical factors of Alzheimer’s disease.A linear interaction between Aβand tau protein has been characterized in several models.Aβinduces tau hyperphosphorylation through a complex mechanism;however,the master regulators involved in this linear process are still unclear.In our study with Drosophila melanogaster,we found that Aβregulated tau hyperphosphorylation and toxicity by activating c-Jun N-terminal kinase.Importantly,Aβtoxicity was dependent on tau hyperphosphorylation,and flies with hypophosphorylated tau were insulated against Aβ-induced toxicity.Strikingly,tau accumulation reciprocally interfered with Aβdegradation and correlated with the reduction in mRNA expression of genes encoding Aβ-degrading enzymes,including dNep1,dNep3,dMmp2,dNep4,and dIDE.Our results indicate that Aβand tau protein work synergistically to further accelerate Alzheimer’s disease progression and may be considered as a combined target for future development of Alzheimer’s disease therapeutics.

Hydrogen Generation from Water Splitting by Catalysts of Platinum-Based Clusters Pt3X(X=Al,Si,Cu)and CO Oxidation by Their By-Products

Reducing sizes of precious metals and utilization of the mixed small clusters of them as catalysts in reactions are important methods due to more active sites for higher catalytic eciency.Based on rst-principles calculations in this work,we found that the platinumbased clusters of Pt3X(X=Al,Si,Cu)which have the magic number 4 can e ectively catalyze the water decomposition and hydrogen production in just one-step reaction process.The adsorbates of the H2O@Pt3X clusters have strong absorption in the ultraviolet and visible regions with wavelength from 300 nm to 760 nm,indicating the sunlight can be used to drive catalytic hydrolysis for producing clean hydrogen.In addition,the O atom remains on the clusters after hydrolysis and can react with CO to form CO2 in activation barrier of 0.34􀀀0.58 eV,showing the recycling ability of the products after hydrolysis for eliminating the"poisoning"CO by oxidation.Moreover,the formed CO2 molecule can be detached from the Pt3X clusters at 323 K.Our results provide interesting guidance for practical designing the useful photocatalysts.

Spin accommodation and reactivity of nickel clusters with oxygen:Aromatic and magnetic metalloxocube Ni_(13)O_(8)^(±)

Due to challenges in preparing pure metal clusters and in controlling reactions,the oxides produced by metal clusters reacting with oxygen are often different from traditional ion-molecule products in the gas phase and their reactivity pattern is also largely unveiled yet.In this work,utilizing a customized Re-TOFMS having a home-made cluster source and a flow tube reactor,we have observed the gaseous reactions of Nin±clusters with oxygen and found magic clusters of Ni_(13)O_(8)±that dominate the mass distributions.By quantum chemistry calculations,we find that both Ni_(13)O_(8)−and Ni_(13)O_(8)+clusters bear a regular cubic structure with 8 oxygen anchoring the eight angles,however,they have rather different spin accommodations.The Ni_(13)O_(8)−clusters have 15 unpaired spin-up electrons exhibiting cubic aromaticity and decent ferromagnetism,while the Ni_(13)O_(8)+clusters take a lower-spin ground state(11 unpaired electrons),with spin-down population on the central Ni atom pertaining to ferrimagnetism.This is a class of metalloxocube clusters that hold properties of aromaticity and ferromagnetism/ferrimagnetism charcterized by a few spin electrons,which embodies the bonding nature of superatomic compounds and enables to develop cluster-genetic materials of multi-functionality.