The antioxidant xanthorrhizol prevents amyloid-β-induced oxidative modification and inactivation of neprilysin

Activity of neprilysin (NEP), the major protease which cleaves amyloid-β peptide (Aβ), is reportedly reduced in the brains of patients with Alzheimer’s disease (AD). Accumulation of Aβ generates reactive oxygen species (ROS) such as 4-hydroxynonenal (HNE), and then reduces activities of Aβ-degrading enzymes including NEP. Xanthorrhizol (Xan), a natural sesquiterpenoid, has been reported to possess antioxidant and anti-inflammatory proper- ties. The present study examined the effects of Xan on HNE- or oligomeric Aβ42-induced ox- idative modification of NEP protein. Xan was added to the HNE- or oligomeric Aβ42-treated SK-N-SH human neuroblastoma cells and then levels, oxidative modification and enzymatic activities of NEP protein were measured. Increased HNE levels on NEP proteins and re- duced enzymatic activities of NEP were observed in the HNE- or oligomeric Aβ42-treated cells. Xan reduced HNE levels on NEP proteins and preserved enzymatic activities of NEP in HNE- or oligomeric Aβ42-treated cells. Xan reduced Aβ42 accumulation and protected neurones against oligomeric Aβ42-induced neurotoxicity through preservation of NEP ac- tivities. These findings indicate that Xan possesses therapeutic potential for the treatment of neurodegenerative diseases, including AD, and suggest a potential mechanism for the neuroprotective effects of antioxidants for the prevention of AD

A homozygous Keap1-knockout human embryonic stem cell line generated using CRISPR/Cas9 mediates gene targeting

Kelch-like ECH-associated protein 1 (keap1) is a cysteine-rich protein that interacts with transcription factor Nrf2 in a redox-sensitive manner, leading to the degradation of Nrf2 (Kim et al., 2014a). Disruption of Keap1 results in the induction of Nrf2-related signaling pathways involving the expression of a set of anti-oxidant and anti-inflammatory genes. We generated biallelic mutants of the Keap1 gene using a CRISPR-Cas9 genome editing method in the H9 human embryonic stem cell (hESC). The Keap1 homozygous-knockout H9 cell line retained normal morphology, gene expression, and in vivo differentiation potential. (C) 2016 The Author(s). Published by Elsevier B.V.

Stability of hydrogenation states of graphene and conditions for hydrogen spillover

The hydrogen spillover mechanism has been discussed in the field of hydrogen storage and is believed to have particular advantage over the storage as metal or chemical hydrides. We investigate conditions for practicality realizing the hydrogen spillover mechanism onto carbon surfaces, using first-principles methods. Our results show that contrary to common belief, types of hydrogenation configurations of graphene (the aggregated all-paired configurations) can satisfy the thermodynamic requirement for room-temperature hydrogen storage. However, the peculiarity of the paired adsorption modes gives rise to a large kinetic barrier against hydrogen migration and desorption. It means that an extremely high pressure is required to induce the migration-derived hydrogenation. However, if mobile catalytic particles are present inside the graphitic interstitials, hydrogen migration channels can open and the spillover phenomena can be realized. We suggest a molecular model for such a mobile catalyst which can exchange hydrogen atoms with the wall of graphene.open151

Serial-multiple mediation of enjoyment and intention on the relationship between creativity and physical activity

The purpose of the present study was to examine a serial-multiple mediation of physical activity (PA) enjoyment and PA intention in the relationship between creativity and PA level (i.e., moderate-to-vigorous PA). A total of 298 undergraduate and graduate students completed a selfreported questionnaire evaluating creativity, PA enjoyment, PA intention, and PA level. Data analysis was conducted using descriptive statistics, Pearson correlation coefficient, ordinary leastsquares regression analysis, and bootstrap methodology. Based on the research findings, both PA enjoyment (β = 0.06; 95% CI [0.003, 0.12]) and PA intention (β = 0.08; 95% CI [0.03, 0.13]) were found to be a mediator of the relationship between creativity and PA level, respectively. Moreover, the serial-multiple mediation of PA enjoyment and PA intention in the relationship between creativity and PA level was statistically significant (β = 0.02; 95% CI [0.01, 0.04]). These findings underscore the importance of shaping both cognitive and affective functions for PA promotion and provide additional support for a neurocognitive affect-related model in the PA domain. In order to guide best practices for PA promotion programs aimed at positively influencing cognition and affect, future PA interventions should develop evidence-based strategies that routinely evaluate cognitive as well as affective responses to PA

The Fit between Client IT Capability and Vendor Competence and Its Impact on Outsourcing Success

This study investigates the impact of client firm’s IT capability, vendor firm’s competence and their fit on the outsourcing success. In theory building, by concretizing the concepts of IT capability and competence based on the resource-based view, the importance of fit between the client’s IT capability and the vendor’s competence is emphasized. We then hypothesize that both factors are stronger together than the individual impact of either the client’s IT capability or the vendor’s competence. For validation, 267 client-vendor-matched-pair data were collected. To avoid potential imbalance caused by the bilateral perspective, an exploratory approach, all-possible-subsets-regression method was adopted. The results reveal that the vendor’s competence is the most significant factor in outsourcing success, but interestingly, the fit between vendor competence and the client’s IT capability is the second most important. The client’s IT capability also has a positive impact on outsourcing success but with the smallest explanation power

Normal modes of coupled vortex gyration in two spatially separated magnetic nanodisks

We found from analytical derivations and micromagnetic numerical simulations that there exist two distinct normal modes in apparently complex vortex gyrotropic motions in two dipolar-coupled magnetic nanodisks. The normal modes have characteristic higher and lower single angular eigenfrequencies with their own elliptical orbits elongated along the x (bonding axis) and y axes, respectively. The superposition of the two normal modes results in coupled vortex gyrations, which depend on the relative vortex-state configuration in a pair of dipolar-coupled disks. This normal-mode representation is a simple means of understanding the observed complex vortex gyrations in two or more dipolar-interacting disks of various vortex-state configurations.Comment: 18 pages, 3 figures, 1 tabl

Total Reflection and Negative Refraction of Dipole-Exchange Spin Waves at Magnetic Interfaces: Micromagnetic Modeling Study

We demonstrated that dipole-exchange spin waves traveling in geometrically restricted magnetic thin films satisfy the same laws of reflection and refraction as light waves. Moreover, we found for the first time novel wave behaviors of dipole-exchange spin waves such as total reflection and negative refraction. The total reflection in laterally inhomogeneous thin films composed of two different magnetic materials is associated with the forbidden modes of refracted dipole-exchange spin waves. The negative refraction occurs at a 90 degree domain-wall magnetic interface that is introduced by a cubic magnetic anisotropy in the media, through the anisotropic dispersion of dipole-exchange spin waves.Comment: 13 pages, 5 figure