Presenilin-2 Mutation Causes Early Amyloid Accumulation and Memory Impairment in a Transgenic Mouse Model of Alzheimer's Disease

In order to clarify the pathophysiological role of presenilin-2 (PS2) carrying the Volga German Kindred mutation (N141I) in a conventional mouse model of Alzheimer's disease (AD) expressing amyloid precursor protein (APP) with the Swedish mutation (Tg2576 line), we generated a double transgenic mouse (PS2Tg2576) by crossbreeding the PS2 mutant with Tg2576 mice. Here, we demonstrate that the PS2 mutation induced the early deposition of amyloid β-protein (Aβ) at 2-3 months of age and progressive accumulation at 4-5 months of age in the brains of the mutant mice. The PS2 mutation also accelerated learning and memory impairment associated with Aβ accumulation at 4-5 months of age in Tg2576 mice. These results suggest that the PS2 mutation causes early cerebral amyloid accumulation and memory dysfunction. PS2Tg2576 mice are a suitable mouse model for studying amyloid-lowering therapies

Molecular Beam Epitaxy of Wurtzite (Ga,Mn)N Films on Sapphire(0001) Showing the Ferromagnetic Behaviour at Room Temperature

Wurtzite (Ga,Mn)N films showing ferromagnetic behaviour at room temperature were successfully grown on sapphire(0001) substrates by molecular beam epitaxy using ammonia as nitrogen source. Magnetization measurements were carried out by a superconducting quantum interference device at the temperatures between 1.8K and 300K with magnetic field applied parallel to the film plane up to 7T. The magnetic-field dependence of magnetization of a (Ga,Mn)N film at 300K were ferromagnetic, while a GaN film showed Pauli paramagnetism like behaviour. The Curie temperatures of a (Ga,Mn)N film was estimated as 940K.Comment: 5 page

Apple Procyanidins Suppress Amyloid β-Protein Aggregation

Procyanidins (PCs) are major components of the apple polyphenols (APs). We previously reported that treatment with PC extended the mean lifespan of Caenorhabditis elegans (Sunagawa et al., 2011). In order to estimate the neuroprotective effects of PC, we investigated the antiaggregative activity of PC on amyloid β-protein (Aβ) aggregation, which is a pathological hallmark of Alzheimer's disease. We herein report that PC significantly suppressed Aβ42 aggregation and dissociated Aβ42 aggregates in a dose-dependent manner, indicating that PC is a potent suppressor of Aβ aggregation. Furthermore, PC significantly inhibited Aβ42 neurotoxicity and stimulated proliferation in PC-12 cells. These results suggested that the PC and AP acted as neuroprotective factors against toxic Aβ aggregates

Switching of magnon parametric oscillation by magnetic field direction

Parametric oscillation occurs when the resonance frequency of an oscillator is periodically modulated. Owing to time-reversal symmetry breaking in magnets, nonreciprocal magnons can be parametrically excited when spatial-inversion symmetry breaking is provided. This means that magnons with opposite propagation directions have different amplitudes. Here we demonstrate switching on and off the magnon parametric oscillation by reversing the external field direction applied to a Y$_3$Fe$_5$O$_{12}$ micro-structured film. The result originates from the nonreciprocity of surface mode magnons, leading to field-direction dependence of the magnon accumulation under a nonuniform microwave pumping. Our numerical calculation well reproduces the experimental result.Comment: 5 pages, 4 figure

Effects of Propofol on Left Ventricular Mechanoenergetics in the Excised Cross-circulated Canine Heart

Although propofol is commonly used for general anesthesia, its direct effects on left ventricular (LV) contractility and energetics remain unknown. Accordingly, we studied the effects of intracoronary propofol on excised cross-circulated canine hearts using the framework of the Emax (a contractility index)-PVA (systolic pressure-volume area, a measure of total mechanical energy)-Vo2 (myocardial oxygen consumption per beat) relationship. We obtained 1) the Vo2-PVA relationship of isovolumic contractions with varied LV volumes at a constant Emax, 2) the Vo2-PVA relationship with varied LV volumes at a constant intracoronary concentration of propofol, and 3) the Vo2-PVA relationship under increased intracoronary concentrations of either propofol or CaCl2 at a constant LV volume to assess the cardiac mechanoenergetic effects of propofol. We found that propofol decreased Emax dose-dependently. The slope of the linear Vo2-PVA relationship (oxygen cost of PVA) remained unchanged by propofol. The PVA-independent Vo2-Emax relationship (oxygen cost of Emax) was the same for propofol and Ca2＋. In conclusion, propofol showed a direct negative inotropic effect on LV. At its clinical concentrations, decreases in contractility by propofol were relatively small. Propofol shows mechanoenergetic effects on the LV that are similar to those of Ca2＋ blockers or ß-antagonists—i.e., it exerts negative inotropic effects without changing the oxygen costs of Emax and PVA

Contractile Properties of Esophageal Striated Muscle: Comparison with Cardiac and Skeletal Muscles in Rats

The external muscle layer of the mammalian esophagus consists of striated muscles. We investigated the contractile properties of esophageal striated muscle by comparison with those of skeletal and cardiac muscles. Electrical field stimulation with single pulses evoked twitch-like contractile responses in esophageal muscle, similar to those in skeletal muscle in duration and similar to those in cardiac muscle in amplitude. The contractions of esophageal muscle were not affected by an inhibitor of gap junctions. Contractile responses induced by high potassium or caffeine in esophageal muscle were analogous to those in skeletal muscle. High-frequency stimulation induced a transient summation of contractions followed by sustained contractions with amplitudes similar to those of twitch-like contractions, although a large summation was observed in skeletal muscle. The results demonstrate that esophageal muscle has properties similar but not identical to those of skeletal muscle and that some specific properties may be beneficial for esophageal peristalsis