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Seizures are increasingly being recognized as the hallmark of Alzheimer's disease (AD). Neuronal hyperactivity can be a consequence of neuronal damage caused by abnormal amyloid β (Aß) depositions. However, it can also be a cell-autonomous phenomenon causing AD by Aß-independent mechanisms. Various studies using animal models have shown that Ca2+ is released from the endoplasmic reticulum (ER) via type 1 inositol triphosphate receptors (InsP3R1s) and ryanodine receptors (RyRs). To investigate which is the main pathophysiological mechanism in human neurons, we measured Ca2+ signaling in neural cells derived from three early-onset AD patients harboring Presenilin-1 variants (PSEN1 p.A246E, p.L286V, and p.M146L). Of these, it has been reported that PSEN1 p.A246E and p.L286V did not produce a significant amount of abnormal Aß. We found all PSEN1-mutant neurons, but not wild-type, caused abnormal Ca2+-bursts in a manner dependent on the calcium channel, Ryanodine Receptor 2 (RyR2). Indeed, carvedilol, an RyR2 inhibitor, and VK-II-86, an analog of carvedilol without the β-blocking effects, sufficiently eliminated the abnormal Ca2+ bursts. In contrast, Dantrolene, an inhibitor of RyR1 and RyR3, and Xestospongin c, an IP3R inhibitor, did not attenuate the Ca2+-bursts. The Western blotting showed that RyR2 expression was not affected by PSEN1 p.A246E, suggesting that the variant may activate the RyR2. The RNA-Seq data revealed that ER-stress responsive genes were increased, and mitochondrial Ca2+-transporter genes were decreased in PSEN1A246E cells compared to the WT neurons. Thus, we propose that aberrant Ca2+ signaling is a key link between human pathogenic PSEN1 variants and cell-intrinsic hyperactivity prior to deposition of abnormal Aß, offering prospects for the development of targeted prevention strategies for at-risk individuals. [ABSTRACT FROM AUTHOR]

Dehydrogenation polymers (DHPs) can be prepared from coniferyl alcohol (CA), but not solely from sinapyl alcohol (SA) when catalyzed by horseradish peroxidase (HRP). However, it has been proven that from a mixture of CA and SA, DHP with SA incorporated can be formed even with HRP. Conventional experiments using this mixed monolignol system required large amounts of monolignols and enzymes. The use of a quartz crystal microbalance with dissipation (QCM-D) can overcome this drawback. In this study, the dehydrogenative copolymerization of small amounts of CA/SA mixtures and HRP was performed on a QCM-D to further explore the benefits of this system. The DHPs were successfully formed from mixed monolignols on the QCM-D system, and the incorporation of the SA unit was verified through differences in DHP formation between binary monolignol systems and the corresponding CA-single systems. The formation of DHP in the presence of the polysaccharide matrix was performed at the same reaction scale, and the promotional effect of partially acetylated xylan on DHP formation was observed, especially at high CA ratios. The QCM-D monitoring system will be a valuable tool for analyses under limited substrates and/or enzymes that may be encountered in the future. [ABSTRACT FROM AUTHOR]

The introduction of large-scale renewable energy requires a control system that can operate multiple distributed inverters in a stable way. This study proposes an inverter control method that uses information corresponding to the inertia of the synchronous generator to coordinate the operation of battery energy storage systems. Simulation results for a system with multiple inverters applying the control method are presented. Various faults such as line-to-line short circuits and three-phase line-to-ground faults were simulated. Two fault points with different characteristics were compared. The voltage, frequency and active power quickly returned to their steady-state values after the fault was eliminated. From the obtained simulation results, it was verified that our control method can be operated stably against various faults. [ABSTRACT FROM AUTHOR]

We studied the spin accumulation signals in phosphorus-doped n+-Si (8 × 1019 cm−3) by measuring the spin transport in three-terminal vertical devices with Fe(3 nm)/Mg(0 and 1 nm)/SiOxNy(1 nm)/n+-Si(001) tunnel junctions, where the amorphous SiOxNy layer was formed by oxnitridation of the Si substrate with radio frequency plasma. Obvious spin accumulation signals were observed at 4–300 K in the spin extraction geometry when the thickness of the Mg insertion layer was 1 nm. We found that by inserting a thin (1 nm) Mg layer, intermixing of Fe and SiOxNy is suppressed, leading to the appearance of the spin accumulation signals, and this result is consistent with the dead layer model recently proposed by our group [S. Sato et al., Appl. Phys. Lett. 107, 032407 (2015)]. We obtained relatively high spin polarization (PS) of electrons tunneling through the junction and long spin lifetime (τS): PS = 16% and τS = 5.6 ns at 4 K and PS = 7.5% and τS = 2.7 ns at 300 K. Tunnel junctions with an amorphous SiOxNy tunnel barrier are very promising for Si-based spintronic devices, since they can be formed by the method compatible with the silicon complementary metal-oxide-semiconductor technology. [ABSTRACT FROM AUTHOR]

The effects of etoposide on body weight, organ weights and the concentrations of putrescine, spermidine and spermine in 14 different tissues were examined in rats that had been given the drug for five consecutive days. Etoposide reduces all polyamines, which are associated with tumor cell growth, in the thymus and reduces polyamines of two kinds in the spleen, heart, small intestine, skeletal muscle and lung but it increases putrescine in the prostate and spleen, and spermine in the large intestine. [ABSTRACT FROM AUTHOR]

The effects of etoposide on body weight, regional weights, and the concentrations of putrescine, spermidine and spermine in the cerebellum, hippocampus, corpus striatum, cortex, the combined regions of the thalamus and hypothalamus and the diencephalon of the brain were examined in rats. Etoposide seems to be a better choice for management of cortical and hippocampal tumors because it reduces polyamines, which are associated with tumor cell growth, but not for the management of tumors of the diencephalon and corpus striatum because it increases polyamines. [ABSTRACT FROM AUTHOR]

A little fewer than thirty Merovingian accounting documents which originated from the Abbey of St Martin of Tours, though fragmentary, provide for the historians of early medieval Europe an unexpected tool with which the latter could cast a new light over actual conditions in tribute collection and the management system for the fiscal administration of the abbey. The present article asks some basic questions about these accounting documents in the hope of casting further light on their form and function: which form did take the documents while they had been used for the collection of dues? At which stage of collecting procedure they served in the abbey as a tool for the keeping of records? When was each document prepared? In which historical context could be placed the birth of fiscal document of the abbey? All of these question are important for an understanding of the history of St Martin's of Tours and of the use of documents in general in the Merovingian era. [ABSTRACT FROM AUTHOR]